Methanol → N-(4-{4-amino-7-[4-(hydroxymethyl)phenyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

HRID 17202Notes

Reaction equation

HRID 17202 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:32]2[CH:37]=[CH:36][C:35]([CH:38]=[O:39])=[CH:34][CH:33]=2)=[CH:4][N:3]=1.[BH4-].[Na+].CO>CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+]>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:32]2[CH:33]=[CH:34][C:35]([CH2:38][OH:39])=[CH:36][CH:37]=2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 18451244N-{4-[4-amino-7-(4-formylphenyl)thieno[3,2-c]pyridin-3-yl]-2-methoxyphenyl}-1-methyl-1H-indole-2-carboxamide

Product 1

HCID 18451248N-(4-{4-amino-7-[4-(hydroxymethyl)phenyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamideYield 35.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Procedure

N-{4-[4-amino-7-(4-formylphenyl)thieno[3,2-c]pyridin-3-yl]-2-methoxyphenyl}-1-methyl-1H-indole-2-carboxamide (Example 2, 0.030 g, 0.056 mmol) was dissolved in N,N-dimethylformamide (0.5 mL). Sodium borohydride (0.006 g, 0.167 mmol) and methanol (0.5 mL) were added, and the reaction mixture was stirred at ambient temperature for 16 h. The mixture was diluted with aqueous sodium carbonate (1 M, 10 mL) and the product was extracted with methanol/dichloromethane (1:33, 3×20 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel, using ethyl acetate-heptane (3:1) as the mobile phase, to afford the title compound (0.011 g, 0.020 mmol) as a white powder. 1H NMR (DMSO-d6, 400 MHz) δ 9.53 (s, 1H), 8.00 (d, 1H), 7.92 (s, 1H), 7.71 (s, 1H), 7.62 (m, 1H), 7.59 (s, 1H), 7.56 (m, 2H), 7.49 (t, 1H), 7.36 (s, 1H), 7.32 (m, 3H), 7.16 (d, 1H), 7.12 (m, 1H), 5.61 (br, 2H), 5.31 (t, 1H), 4.61 (d, 2H), 4.05 (s, 3H), 3.92 (s, 3H); MS: (M−H)− 533.

Workup

  1. extractionthe product was extracted with methanol/dichloromethane (1:33, 3×20 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-b2915b1068a8407abfa24220621fb294
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Reaction notes

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