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

HRID 711469Notes

Reaction equation

HRID 711469 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4](Cl)[N:3]=1.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36].C(N(C(C)C)CC)(C)C.O>C(#N)C.CCOC(C)=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 583175754,6-dichloro-2-[(2,4-dimethoxyphenyl)methyl]-7-fluoro-1H,2H,3H-pyrrolo[3,4-c]pyridin-3-one

Product 1

HCID 86654712tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateYield 46.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4,6-dichloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (4.8 g, 12.93 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (4.16 g, 19.40 mmol) and diisopropylethylamine (3.39 mL, 19.40 mmol) in ACN (20 mL) was stirred at 100° C. for 3 days. Water and EtOAc were added and the aqueous phase was extracted with EtOAc. The organic phases were combined, washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 (Hexane/EtOAc=1/1) to give the title compound as a brown amorphous solid (3.31 g, 46.6%). 1H NMR (500 MHz, CDCl3) δ ppm 1.35-2.02 (m, 17H), 3.80 (s, 3H), 3.84 (s, 3H), 4.01 (br s, 1H), 4.20 (s, 2H), 4.23 (br s, 1H), 4.66 (s, 2H), 4.91 (br s, 1H), 6.40-6.52 (m, 2H), 7.20-7.28 (m, 1H). [M+H] calc'd for C27H34ClFN4O5, 549. found, 549.

Workup

  1. extractionthe aqueous phase was extracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by chromatography on SiO2 (Hexane/EtOAc=1/1)

Sources & evidence

ORD record
ord-1bb3fc6c20d54258bbbe715fe988299d
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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