Pyrrolidine → 5-[3-(1-pyrrolidinylmethyl)phenyl]-3-(1-{[3-(1-pyrrolidinyl)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamide

HRID 2267593Notes

Reaction equation

HRID 2267593 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:15](=[C:16]([C:18]([NH2:20])=[O:19])[CH:17]=2)[NH:14][CH:13]=[C:12]3[CH:21]2[CH2:26][CH2:25][N:24]([S:27]([CH2:30][CH2:31][CH2:32][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)(=[O:29])=[O:28])[CH2:23][CH2:22]2)[CH:6]=[CH:7][CH:8]=1)=O.[NH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.[BH4-].[Na+]>C(Cl)Cl.CO.CC(O)=O>[N:38]1([CH2:1][C:3]2[CH:4]=[C:5]([C:9]3[CH:10]=[C:11]4[C:15](=[C:16]([C:18]([NH2:20])=[O:19])[CH:17]=3)[NH:14][CH:13]=[C:12]4[CH:21]3[CH2:22][CH2:23][N:24]([S:27]([CH2:30][CH2:31][CH2:32][N:33]4[CH2:34][CH2:35][CH2:36][CH2:37]4)(=[O:28])=[O:29])[CH2:25][CH2:26]3)[CH:6]=[CH:7][CH:8]=2)[CH2:42][CH2:41][CH2:40][CH2:39]1

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 590033335-(3-formylphenyl)-3-(1-{[3-(1-pyrrolidinyl)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamide

Product 1

HCID 590033115-[3-(1-pyrrolidinylmethyl)phenyl]-3-(1-{[3-(1-pyrrolidinyl)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamideYield 8.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 5-(3-formylphenyl)-3-(1-{[3-(1-pyrrolidinyl)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamide (45.0 mg/0.086 mmol) in DCM/MeOH (1.0 ml/1.0 ml) was added pyrrolidine (0.043 mL, 0.517 mmol) and 1 drop of AcOH. The reaction mixture was stirred for 2 hr at r.t and then NaBH4 (17.0 mg, 0.086 mmol) was added. The reaction mixture was stirred for 30 min and concentrated and redissolved in 1.5 ml of DMSO. The residue was purified by using a Gilson semi-preparative HPLC system, eluting with 10% B to 80% B, where A=H2O (0.1% trifluoroacetic acid) and B=CH3CN (0.1% trifluoroacetic acid) pumped at 25 mL/min to give the title compound (4 mg, 8%).

Workup

  1. stirringThe reaction mixture was stirred for 30 min
  2. concentrationconcentrated
  3. dissolutionredissolved in 1.5 ml of DMSO
  4. customThe residue was purified
  5. washeluting with 10% B to 80% B, where A=H2O (0.1% trifluoroacetic acid) and B=CH3CN (0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-01d68fe41a6945008a9c91fe90b0d942
Source dataset
uspto-grants-2010_12
Patent number
US07858796B2

Reaction notes

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