Methanol → 5-[5-(1-Azetidinylmethyl)-3-thienyl]-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

HRID 656086Notes

Reaction equation

HRID 656086 reaction equation
[O:1]=[S:2]1(=[O:27])[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:24]([NH2:26])=[O:25])[CH:13]=[C:14]([C:17]4[CH:21]=[C:20]([CH:22]=O)[S:19][CH:18]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.CO.[NH:30]1[CH2:33][CH2:32][CH2:31]1.C([BH3-])#N.[Na+]>CS(C)=O.C(O)(=O)C>[N:30]1([CH2:22][C:20]2[S:19][CH:18]=[C:17]([C:14]3[CH:15]=[C:16]4[C:11](=[C:12]([C:24]([NH2:26])=[O:25])[CH:13]=3)[NH:10][CH:9]=[C:8]4[CH:5]3[CH2:6][CH2:7][S:2](=[O:1])(=[O:27])[CH2:3][CH2:4]3)[CH:21]=2)[CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 4

HCID 887MethanolHCID 10422AzetidineHCID 5003444Sodium cyanoborohydrideHCID 593325693-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide

Product 1

HCID 593327795-[5-(1-Azetidinylmethyl)-3-thienyl]-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamideYield 9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide (105 mg, 0.26 mmol) was diluted in dimethylsulfoxide (0.5 mL) and methanol (0.5 mL) in a 2 dram vial. Azetidine (75 mg, 5 eq) was added, followed by glacial acetic acid (0.3 mL). The mixture was stirred at rt for 1 h, then sodium cyanoborohydride (35 mg, 0.56 mmol, 2.1 eq) was added and the mixture was stirred at rt overnight. The mixture was filtered through a 1 g silica gel pad (commercial, in syringe tube), and the solvent was removed in vacuo. The crude product was re-diluted in a mixture of methanol and DMSO, and purified by ammonium hydroxide Gilson HPLC. The desired fractions were concentrated in an EZ2 Genevac evaporator, giving 10 mg (9%) of title compound.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. filtrationThe mixture was filtered through a 1 g silica gel pad (commercial, in syringe tube)
  3. customthe solvent was removed in vacuo
  4. additionThe crude product was re-diluted in a mixture of methanol and DMSO
  5. custompurified by ammonium hydroxide Gilson HPLC
  6. concentrationThe desired fractions were concentrated in an EZ2 Genevac evaporator

Sources & evidence

ORD record
ord-fc64df5ec2cc491ca6491bd241a4d245
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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