1,1'-Thiocarbonyldiimidazole → tert-butyl 1-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamothioyl)pyrrolidin-3-ylcarbamate

HRID 1969598Notes

Reaction equation

HRID 1969598 reaction equation
Cl.[S:2]([N:12]1[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C:23](N1C=CN=C1)(N1C=CN=C1)=[S:24].[NH:35]1[CH2:39][CH2:38][CH:37]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:36]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[S:2]([N:12]1[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:23]([N:35]3[CH2:39][CH2:38][CH:37]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:46])[CH3:45])[CH2:36]3)=[S:24])[N:20]=[C:15]2[CH:14]=[CH:13]1)([C:5]1[CH:6]=[CH:7][C:8]([CH3:9])=[CH:10][CH:11]=1)(=[O:3])=[O:4]

Participants

6

Reactant 4

HCID 802641,1'-ThiocarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 67068339(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride

Product 1

HCID 58558007tert-butyl 1-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamothioyl)pyrrolidin-3-ylcarbamateYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a slurry of (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride (0.50 g, 1.5 mmol, Example #5, Step C) in DCM (10 mL) at about 0° C. was added TEA (0.226 mL, 1.62 mmol). To the homogeneous reaction mixture was added a solution of 1,1′-thiocarbonyldiimidazole (0.29 g, 1.6 mmol) in DCM (10 mL). After about 30 min, a slurry of tert-butyl pyrrolidin-3-ylcarbamate (0.83 g, 4.4 mmol, TCI) in DCM (10 mL) was added to the reaction mixture. After stirring for about 20 min, the reaction mixture was allowed to warm to ambient temperature. After stirring for about 15 h, saturated aqueous NaHCO3 (30 mL) was added to the reaction mixture. The organic layer was separated, concd in vacuo, and purified by chromatography on silica gel eluting with 20-40% EtOAc in DCM to provide tert-butyl 1-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamothioyl)pyrrolidin-3-ylcarbamate (0.54 g, 69%) as a yellow glass: LC/MS (Table 1, Method a) Rt=2.37 min; MS m/z: 531 (M+H)+.

Workup

  1. stirringAfter stirring for about 15 h
  2. customThe organic layer was separated
  3. customconcd in vacuo, and purified by chromatography on silica gel eluting with 20-40% EtOAc in DCM

Sources & evidence

ORD record
ord-1cf5dba5b5174c2a8a02ec3befa44224
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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