Lithium diisopropylamide → 1-(6-Bromopyridin-3-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol

HRID 1040188노트

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HRID 1040188 반응식
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.[Br:32][C:33]1[N:38]=[CH:37][C:36]([C:39](=[O:41])[CH3:40])=[CH:35][CH:34]=1>C1COCC1>[Br:32][C:33]1[N:38]=[CH:37][C:36]([C:39]([C:19]2[S:20][C:16]([C:14]3[CH:13]=[C:12]([NH:21][C:22]4[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=4)[CH:11]=[C:10]([CH3:9])[CH:15]=3)=[CH:17][N:18]=2)([OH:41])[CH3:40])=[CH:35][CH:34]=1

참가 물질

5

반응물 3

HCID 2724682Lithium diisopropylamideHCID 156681955-Acetyl-2-bromopyridineHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2회

생성물 1

HCID 866582581-(6-Bromopyridin-3-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol수율 21.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-78 °C

실험 절차

THF (10 ml) was cooled to −78° C., and lithium diisopropylamide (4.13 ml, 7.43 mmol) was added. N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 4, 1.00 g, 2.97 mmol) in THF (10 ml) was added dropwise, and the reaction was stirred at −78° C. for 30 min. 1-(6-Bromopyridin-3-yl)ethanone (0.595 g, 2.97 mmol) in THF (5 ml) was subsequently added in one portion. The reaction was stirred for 10 min at −78° C. The dry ice bath was removed, and the reaction was allowed to warm to room temperature. The dark brown reaction mixture was quenched with aqueous saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Chromatography on silica gel (Biotage 100 g SNAP, 0-30% EtOAc/toluene) afforded 1-(6-bromopyridin-3-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol (348 mg, 0.649 mmol, 21.8% yield) as a yellow solid. MS ESI: [M+H]+ m/z 538.0.

후처리

  1. stirringThe reaction was stirred for 10 min at −78° C
  2. customThe dry ice bath was removed
  3. temperatureto warm to room temperature
  4. customThe dark brown reaction mixture was quenched with aqueous saturated NH4Cl
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated

출처 및 근거

ORD 기록
ord-22c5bbe89b6a44feaaf575b65a3f96f5
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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