Lithium diisopropylamide → HCID 67432981, 화합물

HRID 1040202노트

반응식

HRID 1040202 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH:7]=1.[Li+].CC([N-]C(C)C)C.[CH3:32][C:33]1([CH3:44])[C:42](=[O:43])[CH2:41][CH2:40][CH2:39][C:34]21[O:38][CH2:37][CH2:36][O:35]2>C1COCC1.[Cl-].[NH4+]>[CH3:32][C:33]1([CH3:44])[C:42]([C:11]2[S:12][C:8]([C:6]3[CH:5]=[C:4]([NH:13][C:14]4[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)=[CH:9][N:10]=2)([OH:43])[CH2:41][CH2:40][CH2:39][C:34]21[O:35][CH2:36][CH2:37][O:38]2

참가 물질

6

반응물 3

HCID 2724682Lithium diisopropylamideHCID 109977176,6-dimethyl-1,4-dioxaspiro[4.5]decan-7-oneHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

생성물 1

HCID 67432981HCID 67432981, 화합물수율 57.1%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 25517Ammonium Chloride용매

실험 절차

To a stirred solution of INTERMEDIATE 4 (1.09 g, 3.24 mmol) in THF (17 mL) was added LDA (2M, 4.86 mL, 9.72 mmol) dropwise at −78° C. The orange solution was left to stir for 30 min at that temperature, treated with 6,6-dimethyl-1,4-dioxaspiro[4.5]decan-7-one (0.72 g, 3.9 mmol) in THF (4.5 mL) dropwise, and allowed to warm to room temperature as the bath did. The reaction mixture was diluted with saturated ammonium chloride solution, and extracted with EtOAc (3×). The combined organics were washed with brine, dried (sodium sulfate), filtered concentrated, and purified by column chromatography on silica to afford 6,6-dimethyl-7-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-7-ol (964 mg, 1.85 mmol) as a light yellow foam. MS ESI: [M+H]+ m/z 521.1.

후처리

  1. waitThe orange solution was left
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography on silica

출처 및 근거

ORD 기록
ord-9d45d762adf94cb690d67d9e4cc19925
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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