Water → HCID 178502305, 화합물

HRID 2203145노트

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HRID 2203145 반응식
[CH3:1][O:2][C:3](=[O:37])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C:14]([CH3:16])=[CH:13][C@H:12]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[N:21]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57](=[O:72])[NH:58][C:59]3[CH:64]=[C:63]([O:65][C:66]([F:69])([F:68])[F:67])[C:62](Br)=[CH:61][C:60]=3[Cl:71])=[CH:53][N:52]=2)[C@H:47]([CH3:73])[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57](=[O:72])[NH:58][C:59]3[C:60]([Cl:71])=[CH:61][C:62]([C:25]4[CH:26]=[CH:27][C:22]([C:20]5[N:21]=[C:17]([C@@H:12]6[CH:13]=[C:14]([CH3:16])[CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:37])[CH:6]([CH3:8])[CH3:7])[NH:18][CH:19]=5)=[CH:23][CH:24]=4)=[C:63]([O:65][C:66]([F:69])([F:68])[F:67])[CH:64]=3)=[CH:53][N:52]=2)[C@H:47]([CH3:73])[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]

참가 물질

7

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 178502303HCID 178502303, 화합물

생성물 1

HCID 178502305HCID 178502305, 화합물수율 31%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 1140Toluene용매

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온도
90 °C

실험 절차

To a solution of [(S)-2-Methyl-1-((S)-4-methyl-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2,5-dihydro-pyrrole-1-carbonyl)-propyl]-carbamic acid methyl ester (100 mg, 0.20 mmol, Preparation 4) 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)Cl2 CH2Cl2 (13.55 mg, 0.017 mmol) was added and 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 solid, which was purified by silica gel chromatography (12 g silica, EtOAc/hexanes 40 to 100%) to produce the title intermediate (51 mg, 31% yield) as a yellowish colored solid. (m/z): [M+H]+ calcd for C44H50ClF3N8O7 895.34 found 895.3.

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-50df153cc9a64d94888f77a9b43c1a66
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365549B2

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