Water → tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 661040노트

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HRID 661040 반응식
Br[C:2]1[S:6][C:5]([N:7](C(OC(C)(C)C)=O)[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:4][CH:3]=1.[F:36][C:37]1[CH:44]=[CH:43][C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][C:38]=1[C:39]#[N:40].C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:39]([C:38]1[CH:41]=[C:42]([C:2]2[S:6][C:5]([NH:7][CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH2:10][C:11]3[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=3)=[N:4][CH:3]=2)[CH:43]=[CH:44][C:37]=1[F:36])#[N:40]

참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 114023612-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 57634226(S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

생성물 1

HCID 86613766tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

To a solution of (S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.20 g, 0.34 mmol) in 3 mL of dioxane in a microwave safe tube, was added 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.13 g, 0.52 mmol), sodium carbonate, 2 M in water (0.69 mL, 1.4 mmol), and tetrakis(triphenylphosphine) palladium (0.020 g, 0.017 mmol). The mixture was purged with nitrogen for 30 seconds and the tube was sealed. The tube was then heated to 120° C. in a Personal Chemistry microwave unit for 20 minutes. The mixture was diluted with 5 mL of water and extracted twice with 8 mL of EtOAc. The combined organic extracts were washed with 7 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure afforded tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate, mixed with the other two products. The crude mixture was carried on to the next reaction without any further purification.

후처리

  1. customThe mixture was purged with nitrogen for 30 seconds
  2. customthe tube was sealed
  3. additionThe mixture was diluted with 5 mL of water
  4. extractionextracted twice with 8 mL of EtOAc
  5. washThe combined organic extracts were washed with 7 mL of brine
  6. dry with materialdried over MgSO4
  7. filtrationFiltration and concentration under reduced pressure

출처 및 근거

ORD 기록
ord-c9bfd144b6cd406db34c7bdb5685d382
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084479B2

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