Sodium Bicarbonate → HCID 178451889, 화합물

HRID 18351노트

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HRID 18351 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:19][C:18]([C@@H:20]4[CH2:24][CH2:23][CH2:22][N:21]4[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:17][CH:16]=3)=[CH:11][CH:10]=2)O1.I[C:34]1[CH:39]=[CH:38][C:37]([C:40]2[NH:44][N:43]=[C:42]([C@@H:45]3[CH2:49][CH2:48][CH2:47][N:46]3[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH:41]=2)=[CH:36][CH:35]=1.C([O-])(O)=O.[Na+]>COCCOC.O.C(OCC)(=O)C.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>[C:28]([O:27][C:25]([N:21]1[CH2:22][CH2:23][CH2:24][C@H:20]1[C:18]1[NH:19][C:15]([C:12]2[CH:13]=[CH:14][C:9]([C:34]3[CH:39]=[CH:38][C:37]([C:40]4[NH:44][N:43]=[C:42]([C@@H:45]5[CH2:49][CH2:48][CH2:47][N:46]5[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH:41]=4)=[CH:36][CH:35]=3)=[CH:10][CH:11]=2)=[CH:16][N:17]=1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

참가 물질

8

반응물 3

HCID 516892Sodium BicarbonateHCID 56605289(s)-tert-Butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1h-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 178451890HCID 178451890, 화합물

생성물 1

HCID 178451889HCID 178451889, 화합물수율 43%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 22728543Water ethylacetate용매

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온도
80 °C

실험 절차

A mixture of (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (17) (Scheme 9; 0.138 g, 0.314 mmol), (S)-tert-butyl 2-(5-(4-iodophenyl)-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate 8 (0.141 g, 0.321 mmol), NaHCO3 (0.110 g, 1.31 mmol) and Pd(PPh3)4 (0.024 g, 0.0208 mmol) in a mixture of DME (3 mL) and H2O (1 mL) was heated at 80° C. under Ar for 12 hours. The cooled mixture was diluted with ethyl acetate/H2O, the layers separated and the aqueous phase was re-extracted with ethyl acetate (2×). The combined organic layers were washed (H2O, brine) and dried (Na2SO4) and filtered and the solvent was removed in vacuo. The resulting residue was purified by flash chromatography (hexane:ethyl acetate, 2:1 and then ethyl acetate:methanol, 9:1) to give (S)-tert-butyl 2-(5-(4′-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate (19) (0.084 g, 43%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.01, 12.69, 12.20, 11.91, 11.85 (s, 1H), 7.63-7.85 (m, 8H), 7.50-7.56 (m, 1H), 6.52 (s, 1H), 4.75-4.94 (m, 2H), 3.42-3.58 (m, 2H), 3.30-3.39 (m, 2H, partially obscured by H2O signal), 2.10-2.28 (m, 2H), 1.81-2.01 (m, 6H), 1.40 (s, 7H), 1.20-1.23 (m, 6H), 1.13-1.15 (m, 5H). LCMS: Anal. Calcd. for C36H44N6O4: 624. found: 625 (M+H)+.

후처리

  1. customthe layers separated
  2. extractionthe aqueous phase was re-extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed (H2O, brine)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe resulting residue was purified by flash chromatography (hexane

출처 및 근거

ORD 기록
ord-b0860c3b3b514ae890df706f04736235
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741347B2

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