Water → HCID 178502461, 화합물

HRID 1504321노트

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HRID 1504321 반응식
[CH3:1][O:2][C:3](=[O:38])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C@@H:14]([O:16][CH3:17])[CH2:13][C@H:12]1[C:18]1[NH:19][CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[N:22]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([C:58](=[O:73])[NH:59][C:60]3[CH:65]=[C:64]([O:66][C:67]([F:70])([F:69])[F:68])[C:63](Br)=[CH:62][C:61]=3[Cl:72])=[CH:54][N:53]=2)[C@H:48]([CH3:74])[CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40].O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([C:58](=[O:73])[NH:59][C:60]3[C:61]([Cl:72])=[CH:62][C:63]([C:26]4[CH:27]=[CH:28][C:23]([C:21]5[N:22]=[C:18]([C@@H:12]6[CH2:13][C@H:14]([O:16][CH3:17])[CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:38])[CH:6]([CH3:7])[CH3:8])[NH:19][CH:20]=5)=[CH:24][CH:25]=4)=[C:64]([O:66][C:67]([F:70])([F:69])[F:68])[CH:65]=3)=[CH:54][N:53]=2)[C@H:48]([CH3:74])[CH2:47]1)=[O:45])([CH3:42])([CH3:40])[CH3:41]

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 67494940(R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502456HCID 178502456, 화합물

생성물 1

HCID 178502461HCID 178502461, 화합물수율 21%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
90 °C

실험 절차

To a solution of [(S)-1-((2S,4S)-4-methoxy-2-{4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (100 mg, 0.19 mmol, Preparation 27) and (R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (110 mg, 0.19 mmol) dissolved in toluene (1.18 mL) and water (0.43 mL) was added potassium carbonate (127 mg, 0.92 mmol). The reaction mixture was sparged under nitrogen for 15 min and Pd(dppf)Cl2CH2Cl2 (13.55 mg, 0.017 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 90° C. overnight, cooled to RT, diluted with EtOAc and washed with water and brine to produce a dark colored solid, which was purified by silica gel chromatography (12 g silica, EtOAc/hexanes 40 to 100%) to produce the title intermediate (35.3 mg, 21% yield) as a yellowish colored solid. (m/z): [M+H]+ calcd for C44H52ClF3N8O8 913.35. found 913.3.

후처리

  1. customThe reaction mixture was sparged under nitrogen for 15 min
  2. customthe reaction mixture was sparged with nitrogen
  3. temperaturecooled to RT
  4. additiondiluted with EtOAc
  5. washwashed with water and brine
  6. customto produce a dark colored solid, which
  7. customwas purified by silica gel chromatography (12 g silica, EtOAc/hexanes 40 to 100%)

출처 및 근거

ORD 기록
ord-7b02d87a0f654a618aa2d0029573604d
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212168B2

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