Diisopropylethylamine → tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

HRID 1915868노트

반응식

HRID 1915868 반응식
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22](O)=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH2:58][C:59]1[CH:60]=[N:61][N:62]([CH3:79])[C:63]=1[N:64]1[CH2:70][CH2:69][CH:68]([F:71])[CH:67]([NH:72][C:73](=[O:78])[C:74]([F:77])([F:76])[F:75])[CH2:66][CH2:65]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:21][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]([F:20])[C:14]=1[C:12]1[S:13][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[C:10]([C:22](=[O:23])[NH:58][C:59]2[CH:60]=[N:61][N:62]([CH3:79])[C:63]=2[N:64]2[CH2:65][CH2:66][CH:67]([NH:72][C:73](=[O:78])[C:74]([F:75])([F:76])[F:77])[CH:68]([F:71])[CH2:69][CH2:70]2)[N:11]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86680076N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide

생성물 1

HCID 86680075tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate수율 99.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

To a solution of 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (784 mg, 2.2 mmol) in DCM (40 mL) was added PyBOP (1.46 g, 2.8 mmol) and the mixture stirred at room temperature for 30 min. A solution of N-(1-(4-Amino-1-methyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide (647 mg, 2.0 mmol) and DIPEA (0.59 mL, 3.4 mmol) in DCM (40 mL) was then added and the mixture was stirred at room temperature for 16 hr. The mixture was diluted with DCM (60 mL) and washed with water (30 mL). The organic layer was separated, passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as an off-white solid (1.32 g).

후처리

  1. stirringthe mixture was stirred at room temperature for 16 hr
  2. washwashed with water (30 mL)
  3. customThe organic layer was separated
  4. custompassed through a phase separation cartridge
  5. customthe solvent removed under reduced pressure
  6. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

출처 및 근거

ORD 기록
ord-ce1346a39b0d4cf48ac596b7dda64bb7
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08614206B2

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