Pyrrolidine → HCID 25072859, compound

HRID 387385Notes

Reaction equation

HRID 387385 reaction equation
[CH3:1][C:2]1([CH3:29])[CH2:7][CH:6]([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)[CH2:5][CH2:4][S:3]1(=[O:28])=[O:27].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CS(C)=O.C(O)(=O)C>[CH3:1][C:2]1([CH3:29])[CH2:7][CH:6]([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]([CH2:22][N:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)[S:19][CH:18]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:5][CH2:4][S:3]1(=[O:28])=[O:27]

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 59332756HCID 59332756, compound

Product 1

HCID 25072859HCID 25072859, compoundYield 17.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

3-(2,2-Dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide (30 mg, 0.070 mmol) was dissolved in dimethyl sulfoxide (1.5 mL) and put in a microwave vial. The mixture was stirred and 1-2 drops of acetic acid, and pyrrolidine (0.058 mL, 0.697 mmol) was added. Stirred for 30 minutes at 23° C., before adding sodium triacetoxyborohydride polymer bound (299 mg, 0.697 mmol). The vial was sealed using a silicon septum, and the mixture left stirring overnight at 23° C. The mixture was quenched with water, extracted with DCM, the DCM solution was evaporated to dryness, and the resulting mixture was rerun through the same process: 1.5 mL of DMSO, 1 drop of glacial acetic acid, and 0.577 mL of pyrrolidine. Left stirring 30 min and then 299 mg of polymer bound sodium triacetoxyborohydride was added and the mixture was left stirring 16 h. The sodium triacetoxyborohydride polymer bound was removed by filtration. The mixture was dissolved in 1 mL of DMSO, and the product was purified by preparative HPLC(NH4OH buffer). The desired fractions were concentrated, giving 6 mg of the title compound.

Workup

  1. stirringStirred for 30 minutes at 23° C.
  2. customThe vial was sealed
  3. waitthe mixture left
  4. stirringstirring overnight at 23° C
  5. customThe mixture was quenched with water
  6. extractionextracted with DCM
  7. customthe DCM solution was evaporated to dryness
  8. waitLeft
  9. stirringstirring 30 min
  10. additionwas added
  11. waitthe mixture was left
  12. stirringstirring 16 h
  13. customThe sodium triacetoxyborohydride polymer bound was removed by filtration
  14. dissolutionThe mixture was dissolved in 1 mL of DMSO
  15. customthe product was purified by preparative HPLC(NH4OH buffer)
  16. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-a98aba2b20da4024ab4e84797a2e176c
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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