Isoquinoline-3-carboxaldehyde → HCID 58026348, compound

HRID 1910129Notes

Reaction equation

HRID 1910129 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=O)[N:2]=1.[NH:13]1[CH:17]=[CH:16][N:15]=[C:14]1[NH:18][C:19]([C:21]1[C:29]2[NH:28][C:27]([NH2:30])=[N:26][C:25]=2[CH:24]=[CH:23][CH:22]=1)=[O:20].[BH4-].[Na+]>ClCCCl.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[NH:15]1[CH:16]=[CH:17][N:13]=[C:14]1[NH:18][C:19]([C:21]1[C:29]2[N:28]=[C:27]([NH:30][CH2:11][C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)[NH:26][C:25]=2[CH:24]=[CH:23][CH:22]=1)=[O:20]

Participants

6

Reactant 3

HCID 231555Isoquinoline-3-carboxaldehydeHCID 4311764Sodium borohydrideHCID 178508178HCID 178508178, compound2×

Product 1

HCID 58026348HCID 58026348, compoundYield 7.3%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 150 mg (0.95 mmol) of isoquinoline-3-carbaldehyde in dry DCE (1 mL) was added 60 mg (0.25 mmol) of 2-amino-3H-benzoimidazole-4-carboxylic acid (1H-imidazol-2-yl)-amide (intermediate B), and Ti(OiPr)4 (3 mL). The mixture was sonicated for 30 min then stirred at room temperature for 6 h. NaBH4 (0.5 g) was added, and the mixture was stirring for 12 h. The reaction was quenched by addition of methanol (2 mL). After usual workup, the residue was purified by column chromatography eluting with DCM then EtOAc/methanol (v/v=100:5) to give 7 mg (7%) of 2-[(isoquinolin-3-ylmethyl)-amino]-1H-benzoimidazole-4-carboxylic acid (1H-imidazol-2-yl)-amide. LCMS: 384 (M+1)+. 1H NMR (DMSO-d6, 400 MHz): δ 12.58 (s, 1H), 11.8 (s, 1H), 11.6 (s, 1H), 9.07 (s, 1H), 8.69 (s, 1H), 8.22 (t, 1H), 7.96 (d, 1H), 7.91 (d, 1H), 7.67 (m, 2H), 7.53 (t, 1H), 7.36 (d, 1H), 7.02 (t, 1H), 6.90 (s, 1H), 6.85 (s, 1H), 4.78 (d, 2H) ppm.

Workup

  1. customThe mixture was sonicated for 30 min
  2. stirringthe mixture was stirring for 12 h
  3. customThe reaction was quenched by addition of methanol (2 mL)
  4. customAfter usual workup, the residue was purified by column chromatography
  5. washeluting with DCM

Sources & evidence

ORD record
ord-adda322aea444a97b5a0da0c05ade094
Source dataset
uspto-grants-2013_12
Patent number
US08598353B2

Reaction notes

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