Water → tert-Butyl (1S,2R)-2-(7-chloro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 711466Notes

Reaction equation

HRID 711466 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[C:12]3[C:13](=[O:16])[NH:14][CH2:15][C:11]=3[CH:10]=[C:9]([NH:17][C@@H:18]3[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]3[NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[N:8]=2)[CH:4]=[N:3]1.[Cl:32]N1C(=O)CCC1=O.O.C(Cl)(Cl)Cl>C(Cl)Cl>[Cl:32][C:10]1[C:11]2[CH2:15][NH:14][C:13](=[O:16])[C:12]=2[C:7]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)=[N:8][C:9]=1[NH:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]1[NH:24][C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:30])[CH3:29]

Participants

6

Reactant 4

HCID 962WaterHCID 6212ChloroformHCID 31398Chlorosuccinimide2×HCID 86654709tert-Butyl (1S,2R)-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 1

HCID 86654711tert-Butyl (1S,2R)-2-(7-chloro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (1S,2R)-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (30 mg, 0.070 mmol) and N-chlorosuccinimide (9.86 mg, 0.074 mmol) in DCM (1 mL) was stirred at RT overnight. Additional N-chlorosuccinimide (1 eq) was added and the mixture was stirred at RT for 3 h. Water and CHCl3 were added to the mixture and the organic phase was washed with brine, dried over MgSO4, and evaporated. The residue was purified by preparative HPLC to give the title compound (20 mg, 61.7%). 1H NMR (500 MHz, CDCl3) δ ppm 1.18-2.09 (m, 17H), 4.02 (s, 3H), 4.28-4.45 (m, 2H), 5.80 (br s, 1H), 8.39 (br s, 1H), 9.03 (br s, 1H). [M+H] calc'd for C22H29ClN6O3, 461. found, 461.

Workup

  1. washthe organic phase was washed with brine
  2. dry with materialdried over MgSO4
  3. customevaporated
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-77790b3fcb8047e2b9ccf9dbd0d03dce
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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