References and Notes
1a
Breslow R.
J. Am. Chem. Soc.
1958,
80:
3719
1b
Olofson RA.
Thompson WR.
Michelman JS.
J. Am. Chem. Soc.
1964,
86:
1865
1c
Amyes TL.
Diver ST.
Richard JP.
Rivas FM.
Toth K.
J. Am. Chem. Soc.
2004,
126:
4366
2
Nolan SP.
N-Heterocyclic
carbenes in synthesis
Wiley-VCH;
Weinheim:
2006.
3a
Hlasta DJ.
Org. Lett.
2001,
3:
157
3b
Deng Y.
Hlasta DJ.
Tetrahedron lett.
2002,
43:
189
3c
Deng Y.
Hlasta DJ.
Org. Lett.
2002,
4:
4017
3d
Zificsak CA.
Hlasta DJ.
Tetrahedron
Lett.
2005,
46:
4789
4a
Trofimov BA.
Andriyankova LV.
Belyaeva KV.
Mal’kina AG.
Nikitina LP.
Afonin AV.
Ushakov
IA.
Eur. J. Org. Chem.
2010,
1772
4b
Cruz-Acosta F.
de Armas P.
Garcia-Tellado F.
Synlett
2010,
2421
5
Regel E.
Büchel K.-H.
Justus Liebigs Ann.
Chem.
1977,
145
6
Regel E.
Justus
Liebigs Ann. Chem.
1977,
159
7a
Hlasta DJ.
Tetrahedron Lett.
1990,
31:
5833
7b
Hlasta DJ.
Silbernagel MJ.
Heterocycles
1998,
48:
1015
8
Johnson AL.
J.
Org. Chem.
1976,
41:
836
9a
O’Shaughnessy J.
Cunningham D.
Kavanagh P.
Leech D.
McArdle P.
Aldabbagh F.
Synlett
2004,
2382
9b
Lynch MP.
Hehir S.
Kavanagh P.
Leech D.
O’Shaughnessy J.
Carty MP.
Aldabbagh F.
Chem. Eur. J.
2007,
13:
3218
9c
Moriarty E.
Carr M.
Bonham S.
Carty MP.
Aldabbagh F.
Eur.
J. Med. Chem.
2010,
45:
3762
10
Fagan V.
Bonham S.
Carty MP.
Aldabbagh F.
Org. Biomol. Chem.
2010,
8:
3149
11
General Procedure
for Annulation: Carboxylic acid 1a-d (0.79 mmol) in Ac2O (50 mL)
was heated under reflux for 15 min. The mixture was stirred at r.t.
for 18 h, and evaporated to dryness for 3a, 3b and 3d. Ac2O
was evaporated immediately after the reflux, and the dry residue
(sample purified
[¹²]
)
heated in air at 50 ˚C for 18 h for 3c. Residues were purified by dry column
vacuum chromatography¹0,¹6 using silica
gel as absorbent with gradient elution of hexane, EtOAc and MeOH
as eluent
12
11-Hydroxy-1,4-dimethoxybenzimidazo[1,2-
b
]-isoquinolin-6
(11
H
)-one
(8a): Yellow solid; R
f
= 0.63 (EtOAc-MeOH,
9:1); mp 197-200 ˚C (dec.); IR (neat): 2927,
1676 (C=O), 1601, 1525, 1502, 1431, 1340, 1282, 1257, 1226,
1178, 1158, 1108, 1037 cm-¹;
¹H NMR (400 MHz,
CDCl3): δ = 8.37 (d, J = 8.0 Hz,
1 H), 7.82-7.75 (m, 2 H, 8,9-H), 7.63-7.60
(m, 1 H), 7.09 (s, 1 H, 11-H), 6.81 (d, J = 8.6 Hz,
1 H, 2,3-H), 6.62 (d, J = 8.6 Hz,
1 H, 2,3-H), 5.44 (br. s, 1 H, OH, disappears
with D2O), 4.11 (s, 3 H, CH3), 3.98
(s, 3 H, CH3); ¹³C
NMR (100 MHz, CDCl3): δ = 174.1 (C=O),
148.3, 141.8, 140.0, 138.0, 136.3 (all C), 134.4 (8,9-CH), 130.3
(C), 130.0 (CH), 128.7 (8,9-CH), 127.5 (CH), 125.1 (C), 106.6 (2,3-CH),
103.8 (2,3-CH), 76.8 (11-CH), 56.7 (CH3), 56.3 (CH3); HRMS (ESI): m/z calcd for C17H15N2O4:
311.1032; found: 311.1018 [M + H]+.
1,4-Dimethoxy-6-oxo-6,11-dihydrobenzimidazo[1,2-
b
]isoquinolin-11-yl
acetate (8b): Yellow solid; R
f
= 0.56 (EtOAc);
mp 171-174 ˚C (dec.); IR (neat): 2922,
2847, 1746 (C=O), 1679 (C=O), 1599, 1527, 1506,
1455, 1418, 1367, 1354, 1290, 1263, 1204, 1180, 1108, 1079, 1009 cm-¹;
¹H NMR (400 MHz,
CDCl3): δ = 8.43 (s, 1 H,
11-H), 8.36 (dd, J = 7.8,
1.4 Hz, 1 H), 7.93 (d, J = 7.7 Hz,
1 H), 7.74-7.71 (m, 1 H, 8,9-H), 7.66-7.63
(m, 1 H, 8,9-H), 6.76 (d, J = 8.6 Hz,
1 H, 2,3-H), 6.65 (d, J = 8.6 Hz,
1 H, 2,3-H), 4.01 (s, 3 H, CH3), 3.91
(s, 3 H, CH3), 2.01 (s, 3 H, COOCH3); ¹³C
NMR (100 MHz, CDCl3): δ = 174.1 (C=O), 169.9
(C=O), 147.8, 143.2, 141.6, 136.6, 136.1 (all C), 134.7 (8,9-CH),
130.8 (C), 130.6 (8,9-CH), 128.9 (CH), 127.8 (CH), 124.9 (C), 106.9
(2,3-CH), 104.4 (2,3-CH), 76.0 (11-CH), 56.4 (CH3), 55.9
(CH3), 21.2 (COOCH3); HRMS (ESI): m/z calcd for C19H17N2O5:
353.1137; found: 353.1124 [M + H]+
.
13
Benzimidazo[1,2-
b
]isoquinoline-1,4,6,11-tetrone
(9): CAN (0.296 g, 0.54 mmol) in H2O (5 mL) was
added to 3c (83 mg, 0.27 mmol) in MeCN
(20 mL) at -5 ˚C. After 5 min, H2O
(20 mL) was added and the product was extracted with CH2Cl2 (30
mL). The organic extract was evaporated to dryness and the residue
was recrystallized from CHCl3. Yield: 60 mg (79%);
brown solid; mp 203-205 ˚C (dec.); IR (neat):
1752 (C=O), 1684 (C=O), 1671 (C=O), 1583,
1515, 1494, 1396, 1358, 1287, 1259, 1239, 1189, 1062 cm-¹; ¹H NMR
(400 MHz, DMSO-d
6): δ = 8.32-8.30
(m, 1 H), 8.22-8.20 (m, 1 H), 8.01-7.99
(m, 2 H, 8,9-H), 6.98 [d (AB-q), J = 10.3 Hz,
1 H, 2,3-H], 6.93 [d (AB-q), J = 10.3 Hz,
1 H, 2,3-H]; ¹³C
NMR (100 MHz, DMSO-d
6): δ = 181.3,
175.6, 173.7, 157.2 (all C=O), 146.6 (C), 143.4 (C), 139.1
(2,3-CH), 136.0 (8,9-CH), 135.9 (8,9-CH), 135.8 (2,3-CH), 132.8,
131.0, 130.3 (all C), 130.1 (CH), 127.4 (CH); HRMS (ESI): m/z calcd
for C15H7N2O4: 279.0406;
found: 279.0400 [M + H]+
.
14 CCDC 805313 contains the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data _request/cif,
or by emailing data_request@ccdc.cam.ac.uk
or by contacting The Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033
15
Methyl 3-[(4,7-Dioxo-4,7-dihydro-1
H
-benzimidazol-2-yl)carbonyl]pyridine-2-carboxylate
(11): Synthesis as described previously¹³ with
the residue recrystallized using EtOAc and hexane. Yield: 72 mg
(86%); brown solid; mp 109-111 ˚C;
IR (neat): 3408, 1671 (C=O), 1623 (C=O), 1436,
1290, 1062, 1037 cm-¹; ¹H
NMR (400 MHz, CD3OD): δ = 8.83 (d, J = 3.6 Hz,
1 H, Pyr-6-H), 8.22 (d, J = 7.5 Hz, 1 H,
Pyr-4-H), 7.86-7.83 (m, 1 H, Pyr-5-H), 6.78 (s,
2 H, BnIm-5,6-H), 3.75 (s, 3 H, CH3),
NH not observed; ¹³C NMR (100 MHz,
CD3OD): δ = 184.1, 179.5 (×2),
165.3 (all C=O), 150.6 (Pyr-6-CH), 148.2 (C), 146.4 (C),
138.3 (Pyr-4-CH), 137.3 (2 × C), 137.0
(BnIm-5,6-CH), 135.4 (C), 127.2 (Pyr-5-CH), 52.5 (CH3);
HRMS (ESI): m/z calcd
for C15H10N3O5: 312.0620;
found: 312.0630 [M + H]+.
16a
Harwood LM.
Aldrichimica Acta
1985,
18:
25
16b
Pedersen DS.
Rosenbohm C.
Synthesis
2001,
2431
