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

HRID 516005Notes

Reaction equation

HRID 516005 reaction equation
Cl[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:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:45][N:46]1[CH:50]=[C:49](B2OC(C)(C)C(C)(C)O2)[CH:48]=[N:47]1.CCOC(C)=O>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:21][O:20][C:13]1[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:12]=1[CH2:11][N:9]1[CH2:10][C:6]2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]3[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=[C:2]([C:49]3[CH:48]=[N:47][N:46]([CH3:45])[CH:50]=3)[C:7]=2[C:8]1=[O:22]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 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)cyclohexylcarbamate

Product 1

HCID 86654713tert-Butyl (1S,2R)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateYield 40.7%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 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 (200 mg, 0.364 mmol), sodium carbonate (77 mg, 0.729 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (91 mg, 0.437 mmol) and bis(triphenylphosphine)palladium chloride (25.6 mg, 0.036 mmol) in DME (2 mL) and H2O (0.667 mL) was stirred at 85° C. for 2 h. To the resulting mixture was added EtOAc. 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=2/3) to give the title compound as a yellow oil (88 mg, 40.6%). 1H NMR (500 MHz, CDCl3) δ ppm 1.28-2.01 (m, 17 H), 3.80 (d, J=2.93 Hz, 3 H), 3.85 (s, 3 H), 3.91-4.01 (m, 4 H), 4.23 (br s, 2 H), 4.41 (br s, 1 H), 4.68 (d, J=1.95 Hz, 2 H), 5.36 (br s, 1 H), 6.36-6.54 (m, 2 H), 7.15-7.21 (m, 1 H), 8.26 (br s, 1 H), 9.02 (br s, 1 H). [M+H] calc'd for C31H39FN6O5, 595; found, 595.

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=2/3)

Sources & evidence

ORD record
ord-0bf109512b45491b83d06a3246ce1e15
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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