Water → HCID 178502502, 화합물

HRID 2203146노트

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HRID 2203146 반응식
[CH3:1][O:2][C:3](=[O:38])[NH:4][C@H:5]([C:9]([N:11]1[C@H:15]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24](B4OC(C)(C)C(C)(C)O4)=[CH:23][CH:22]=3)[N:20]=2)[CH2:14][Si:13]([CH3:37])([CH3:36])[CH2:12]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:24]4[CH:23]=[CH:22][C:21]([C:19]5[N:20]=[C:16]([C@H:15]6[N:11]([C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:38])[CH:6]([CH3:7])[CH3:8])[CH2:12][Si:13]([CH3:37])([CH3:36])[CH2:14]6)[NH:17][CH:18]=5)=[CH:26][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 178502500HCID 178502500, 화합물

생성물 1

HCID 178502502HCID 178502502, 화합물수율 26%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
90 °C

실험 절차

To a solution of [[(5)-1-((R)-3,3-dimethyl-5-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-[1,3]azasilolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methylester (51.6 mg, 0.096 mmol; Preparation 11) and (R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (56.7 mg, 0.096 mmol) dissolved in toluene (0.61 mL) and water (0.24 mL) was added potassium carbonate (66.0 mg, 0.48 mmol). The reaction mixture was sparged under nitrogen for 15 min and Pd(dppf)Cl2CH2Cl2 (7.02 mg, 0.009 mmol) was added. The reaction mixture was sparged with nitrogen and heated to 90° C. overnight, cooled to RT, diluted with EtOAc, and washed with water and brine to produce a dark colored oil. The residue was purified by silica gel chromatography (12 g silica, 0% to 100% EtOAc/hexane) to produce the title intermediate as a yellowish solid (23 mg; 26% yield) (m/z): [M+H]+ calcd for C44H54ClF3N8O7Si, 927.35 found 927.4.

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 oil
  7. customThe residue was purified by silica gel chromatography (12 g silica, 0% to 100% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-64bcf91909304a2c99dcb3cdfd00f680
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365549B2

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