Sodium borohydride → N-(4-{4-amino-7-[5-(hydroxymethyl)-2-furyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

HRID 2390701Notes

Reaction equation

HRID 2390701 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[O:33][C:34]([CH:37]=[O:38])=[CH:35][CH:36]=2)=[CH:4][N:3]=1.[BH4-].[Na+]>CN(C)C=O.CO>[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[O:33][C:34]([CH2:37][OH:38])=[CH:35][CH:36]=2)=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 18451275N-{4-[4-amino-7-(5-formyl-2-furyl)thieno[3,2-c]pyridin-3-yl]-2-methoxyphenyl}-1-methyl-1H-indole-2-carboxamide

Product 1

HCID 18451278N-(4-{4-amino-7-[5-(hydroxymethyl)-2-furyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamideYield 3.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of N-{4-[4-amino-7-(5-formyl-2-furyl)thieno[3,2-c]pyridin-3-yl]-2-methoxyphenyl}-1-methyl-1H-indole-2-carboxamide (0.060 g, 0.12 mmol) and sodium borohydride (0.013 g, 0.344 mmol) in N,N-dimethylformamide (4 mL) and methanol (4 mL) was stirred at ambient temperature for 18 hours. The solvent was removed in vacuo and the residue was partitioned between dichloromethane (10 mL) and 0.1 N hydrochloric acid (10 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over anhydrous magnesium sulfate and the solvent was removed in vacuo. The residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 25 cm; 40% acetonitrile-0.1M ammonium acetate isocratic for 5 minutes, then 40-100% acetonitrile-0.1M ammonium acetate over 30 min, 21 ml/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyophilized to give the title compound (2.1 mg, 0.004 mmol) as a white solid.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between dichloromethane (10 mL) and 0.1 N hydrochloric acid (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (3×10 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 25 cm
  8. wait40% acetonitrile-0.1M ammonium acetate isocratic for 5 minutes
  9. wait40-100% acetonitrile-0.1M ammonium acetate over 30 min
  10. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-7d664060ae0343f5b325d303b1878b3e
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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