1,2-Dichloroethane → N-(6-(2-cyanopropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride

HRID 576212ノート

反応式

HRID 576212 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:13]([F:16])([F:15])[F:14])[C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[N:6][CH:7]=1.[CH2:17]([O:19][C:20]1[C:25](=[O:26])[NH:24][CH:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([CH2:33][C:34](O)=[O:35])=[C:29]([F:37])[CH:28]=2)[CH:21]=1)[CH3:18].C1C=CC2N(O)N=NC=2C=1.C(Cl)C[Cl:50].CCN(CC)CC>CN(C=O)C>[ClH:50].[C:9]([C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:1][C:34](=[O:35])[CH2:33][C:30]2[CH:31]=[CH:32][C:27]([C:22]3[CH:21]=[C:20]([O:19][CH2:17][CH3:18])[C:25](=[O:26])[NH:24][CH:23]=3)=[CH:28][C:29]=2[F:37])=[CH:3][C:4]=1[C:13]([F:16])([F:14])[F:15])([CH3:12])[CH3:11])#[N:10]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 904154342-(4-(5-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acidHCID 904159142-(5-Amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropanenitrile

生成物 1

HCID 90423327N-(6-(2-cyanopropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride収率 26.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

A suspension of 2-(5-amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropanenitrile (13.91 mg, 0.061 mmol) in DMF (5 mL) was added to a solution of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid (52 mg, 0.061 mmol) in DMF (5 mL). HOBt (13.94 mg, 0.091 mmol), EDC (17.45 mg, 0.091 mmol) and Et3N (0.025 mL, 0.182 mmol) and the mixture was at 50° C. for 12 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition) to yield an off white solid of N-(6-(2-cyanopropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride (8.62 mg, 0.016 mmol, 26.4% yield). TLC (DCM/MeOH=10:1, Rf=0.3): 1H NMR (400 MHz, CD3OD) δ: 8.95 (d, J=2.2 Hz, 1H), 8.56 (d, J=2.4 Hz, 1H), 7.26-7.47 (m, 5H), 4.14 (q, J=7.0 Hz, 2H), 3.81-3.90 (m, 2H), 1.77-1.91 (m, 6H), 1.47 (t, J=6.9 Hz, 3H); ES-LCMS m/z 503.1 (M+H).

後処理

  1. concentrationThen the solution was concentrated
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition)

出典と根拠

ORDレコード
ord-8d121ad9e73d46609df6cadfb94bd7c0
出典データセット
uspto-grants-2015_05
特許番号
US09035063B2

反応ノート

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