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1,2-Dichloroethane → (1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-N-[3-(2-oxopyrrolidin-1-yl)propyl]cyclohexanecarboxamide

HRID 410536
ノート
印刷プレビュー

反応式

HRID 410536 の反応式
[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)[C:4]([CH3:12])([CH3:11])[CH2:3]1.[NH2:36][CH2:37][CH2:38][CH2:39][N:40]1[CH2:44][CH2:43][CH2:42][C:41]1=[O:45].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O>[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:32])([F:33])[F:34])[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]([NH:36][CH2:37][CH2:38][CH2:39][N:40]2[CH2:44][CH2:43][CH2:42][C:41]2=[O:45])=[O:10])[C:4]([CH3:12])([CH3:11])[CH2:3]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 821111-(3-Aminopropyl)-2-pyrrolidinoneHCID 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

生成物 1

HCID 53251505
(1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-N-[3-(2-oxopyrrolidin-1-yl)propyl]cyclohexanecarboxamide
収率 76%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To (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 (102 mg, 0.20 mmol), N-(3-aminopropyl)-2-pyrrolidinone (85 μL, 0.60 mmol), EDC (58 mg, 0.30 mmol), and HOBt (46 mg, 0.30 mmol) was added N,N-dimethylformamide (2 mL) and triethylamine (140 μL, 1.01 mmol). The mixture was stirred at room temperature for 16 h, quenched with 1:1 water:brine, and extracted with EtOAc. The organic layer was washed with 1:1 water:brine (3×). The organic layer was dried over magnesium sulfate, filtered and purified by reverse phase HPLC(C-18, eluting with a 45:55 to 80:20 gradient of acetonitrile:water+0.1% TFA). The combined fractions were diluted with ethyl acetate and dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated to afford the title compound (97 mg, 0.15 mmol, 76% yield) as a white solid. MS ESI: [M+H]+ m/z 631.2. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.83 (d, J=4.9, 1H), 7.93 (s, 1H), 7.92 (s, 1H), 7.68 (t, J=5.6, 1H), 7.46 (s, 1H), 7.28 (d, J=4.9, 1H), 7.14 (s, 1H), 5:86 (s, 1H), 3.29 (s, 1H), 3.24-3.12 (m, 2H), 3.12-3.03 (m, 1H), 2.99-2.88 (m, 1H), 2.31 (s, 3H), 2.19 (m, 2H), 2.02 (m, 2H), 1.86 (m, 5H), 1.66-1.50 (m, 3H), 1.40 (m, 1H), 1.11 (s, 3H), 0.92 (s, 3H).

後処理

  1. customquenched with 1:1 water
  2. extractionbrine, and extracted with EtOAc
  3. washThe organic layer was washed with 1:1 water
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. custompurified by reverse phase HPLC(C-18
  7. washeluting with a 45:55 to 80:20 gradient of acetonitrile
  8. additionThe combined fractions were diluted with ethyl acetate and dichloromethane
  9. washwashed with saturated aqueous sodium bicarbonate solution
  10. customThe organic layer was separated
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

出典と根拠

ORDレコード
ord-eec89980bbfa4b61b95d206036ed5e45
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08759366B2

反応ノート

読み込み中…

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