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N-Bromosuccinamide → (1S,4R)-4-[5-(2-bromo-3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid

HRID 1040145
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HRID 1040145 반응식
[OH:1][C@:2]1([C:13]2[S:14][C:15]([C:18]3[CH:23]=[C:22]([NH:24][C:25]4[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=4)[CH:21]=[C:20]([CH3:35])[CH:19]=3)=[CH:16][N:17]=2)[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=[O:9])[C:4]([CH3:12])([CH3:11])[CH2:3]1.[Br:36]NC(=O)CCC(N)=O>C(Cl)(Cl)Cl>[Br:36][C:19]1[C:20]([CH3:35])=[CH:21][C:22]([NH:24][C:25]2[N:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[CH:27][N:26]=2)=[CH:23][C:18]=1[C:15]1[S:14][C:13]([C@@:2]2([OH:1])[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=[O:9])[C:4]([CH3:11])([CH3:12])[CH2:3]2)=[N:17][CH:16]=1
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4

반응물 2

HCID 9834204N-BromosuccinamideHCID 53251506(1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid

생성물 1

HCID 58456101(1S,4R)-4-[5-(2-bromo-3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid수율 38.4%

시약·촉매·용매 1

HCID 6212
Chloroform
용매

실험 절차

To a suspension of (1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (example 42(1), 50 mg, 0.099 mmol) in chloroform (800 μL) was added N-bromosuccinamide (21 mg, 0.12 mmol). The mixture was stirred at room temperature for 15 minutes, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (Biotage 10 G, eluting with 1:99 to 10:90 methanol:dichloromethane) to give (1S,4R)-4-[5-(2-bromo-3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (22 mg, 0.038 mmol, 38% yield) as a pale yellow solid. ESI: [M+H]+ m/z 587.1. 1H NMR (500 MHz, CD3OD) δ 8.70 (d, J=4.9, 1H), 7.86 (d, J=2.6, 1H), 7.78-7.64 (m, 2H), 7.13 (d, J=4.9, 1H), 2.46 (s, 3H), 2.35 (dd, J=2.9, 12.8, 1H), 2.22 (ddd, J=6.1, 13.2, 24.2, 1H), 2.01 (dd, J=6.7, 14.5, 3H), 1.79 (d, J=14.4, 1H), 1.72 (dd, J=3.2, 13.5, 1H), 1.22 (s, 3H), 1.11 (s, 3H). rhSYK activity=+++

후처리

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by column chromatography on silica gel (Biotage 10 G, eluting with 1:99 to 10:90 methanol:dichloromethane)

출처 및 근거

ORD 기록
ord-366761acebb84fd6a2e8e6a9d6e6f92f
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08551984B2

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