Potassium Carbonate → HCID 178455333, 화합물

HRID 389605노트

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HRID 389605 반응식
[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[N:24][C:23]([NH2:26])=[C:22]4[O:27][C:28](Cl)=[CH:29][C:21]=34)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:31][C:32]([F:47])([F:46])[C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[F:31][C:32]([F:46])([F:47])[C:33]1[CH:34]=[C:35]([C:28]2[O:27][C:22]3=[C:23]([NH2:26])[N:24]=[CH:25][C:20]([C:18]4[CH:17]=[N:16][N:15]([C@H:12]5[CH2:13][CH2:14][C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10][CH2:11]5)[CH:19]=4)=[C:21]3[CH:29]=2)[CH:36]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:38]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 1562653,5-Bis-trifluoromethylphenylboronic acidHCID 178455334HCID 178455334, 화합물

생성물 1

HCID 178455333HCID 178455333, 화합물수율 92.5%

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A mixture of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chlorofuro[2,3-c]pyridin-7-amine (83 mg, 0.18 mmol), 3,5-bis(trifluoromethyl)benzeneboronic acid (71 mg, 0.28 mmol), (1,1′-bis-(diphenylphosphino)ferrocene)palladium dichloride (13.5 mg, 0.0186 mmol), and potassium carbonate (77 mg, 0.56 mmol) in 1,4-dioxane (1.0 mL) and water (0.30 mL) was degassed 3× with argon and heated in a microwave reactor at 100° C. for 1 h. The mixture was partitioned between EtOAc and brine and the aqueous phase was extracted with EtOAc. The combined organic fractions were dried over sodium sulfate and concentrated. Purification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM) afforded 104 mg (90%) of the title compound as a foam. 1H NMR (400 MHz, CDCl3): δ 0.06-0.14 (m, 6H) 0.87-0.98 (m, 9H) 1.49-1.64 (m, 2H) 1.85-2.11 (m, 4H) 2.18-2.33 (m, 2H) 3.69-3.82 (m, 2H), 4.17-4.28 (m, 1H), 5.05 (br. s., 1H) 7.34 (s, 1H) 7.70 (s, 1H) 7.82 (s, 1H) 7.92 (s, 1H) 8.00 (s, 1H) 8.31 (s, 2H); MS (ESI): 624.34 [M+H]+; HPLC tR=2.00 min (TOF: nonpolar—3 min).

후처리

  1. customwas degassed 3× with argon
  2. customThe mixture was partitioned between EtOAc and brine
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialThe combined organic fractions were dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM)

출처 및 근거

ORD 기록
ord-d111da58ca0e49f49745af4974f11769
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08378104B2

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