1,2-Dichloroethane → 2-[4-(1-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

HRID 254714

反応式

HRID 254714 の反応式
[OH:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=O)=[CH:7][CH:6]=1)([CH3:4])[CH3:3].Cl.Cl.[F:17][C:18]([F:31])([F:30])[CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([C@H:27]([NH2:29])[CH3:28])=[N:25][CH:26]=1.C(Cl)CCl.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[OH:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C:12]([NH:29][C@@H:27]([C:24]2[CH:23]=[CH:22][C:21]([O:20][CH2:19][C:18]([F:31])([F:17])[F:30])=[CH:26][N:25]=2)[CH3:28])=[O:14])=[CH:9][CH:10]=1)([CH3:3])[CH3:4]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 66892447(1R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethan-1-amine dihydrochlorideHCID 66892875HCID 66892875、化合物

生成物 1

HCID 247654782-[4-(1-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide収率 50%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of [4-(1-hydroxy-1methylethyl)phenyl]acetic acid (266 mg, 1.37 mmol), (1R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethylamine bis-hydrochloride (400 mg, 1.37 mmol), EDC (315 mg, 1.64 mmol), and 1-hydroxy-7-azabenzotriazole (224 mg, 1.64 mmol) in DMF (20 mL) was added N,N-diisopropylethylamine (741 uL, 4.25 mmol). The reaction mixture was stirred at room temperature overnight, then concentrated to ˜5 mL and diluted with CH2Cl2 (50 mL). The solution was washed with water (50 mL) and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic layer was washed with water (50 mL), dried over MgSO4, concentrated and purified by normal phase chromatography (15-100% EtOAc/Hexanes) to give 270 mg (50%) of 2-[4-(1-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.20 (d, J=2.75 Hz, 1H), 7.45 (m, 2H), 7.22 (m, 4H), 6.68 (d, J=7.33 Hz, 1H), 5.11 (quint. J=6.96 Hz, 1H), 4.38 (q, J=8.00 Hz, 2H), 3.57 (s, 2H), 1.59 (s, 6H), 1.40 (d, J=6.77 Hz, 3H); MS (Electrospray): m/z 397.3 (M+H).

後処理

  1. concentrationconcentrated to ˜5 mL
  2. additiondiluted with CH2Cl2 (50 mL)
  3. washThe solution was washed with water (50 mL)
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×30 mL)
  5. washThe combined organic layer was washed with water (50 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. custompurified by normal phase chromatography (15-100% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-a160183e7a094413b3b904cf4d54ba25
出典データセット
uspto-grants-2011_01
特許番号
US07875636B2

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