Sodium Carbonate → tert-butyl (1S,2R)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-4-(pyrazolo[1,5-a]pyridin-3-yl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 711472노트

반응식

HRID 711472 반응식
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.CC1(C)C(C)(C)OB([C:47]2[CH:48]=[N:49][N:50]3[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=23)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=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:47]3[CH:48]=[N:49][N:50]4[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=34)[C:7]=2[C:8]1=[O:22]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 583859483-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridineHCID 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

생성물 1

HCID 86654714tert-butyl (1S,2R)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-4-(pyrazolo[1,5-a]pyridin-3-yl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate수율 46.2%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

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 (100 mg, 0.182 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (53.4 mg, 0.219 mmol), sodium carbonate (48.3 mg, 0.455 mmol) and tetrakis(triphenylphosphine)palladium (21.05 mg, 0.018 mmol) in DME (1 mL) and H2O (0.333 mL) was stirred at 85° C. for 3 h. Following reaction, the mixture was filtered and the filtrate was diluted with EtOAc and H2O. 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 to give the title compound (53 mg, 46.1%). 1H NMR (500 MHz, CDCl3) δ ppm 1.17-2.03 (m, 17H), 3.74-3.81 (m, 3H), 3.84-3.89 (m, 3H), 4.04 (br s, 1H), 4.26 (br s, 2H), 4.46 (br s, 1H), 4.71 (br s, 2H), 6.36-6.55 (m, 2H), 6.83 (d, J=5.86 Hz, 1H), 7.18-7.31 (m, 2H), 8.42 (br s, 1H), 8.47-8.57 (m, 1H), 9.42 (br s, 1H).

후처리

  1. customreaction
  2. filtrationthe mixture was filtered
  3. additionthe filtrate was diluted with EtOAc and H2O
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe residue was purified by chromatography on SiO2

출처 및 근거

ORD 기록
ord-f387f8a54757425fa919ce0a2f7e2526
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181255B2

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