1,2-Dichloroethane → HCID 86673010、化合物

HRID 410662ノート

反応式

HRID 410662 の反応式
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:36])[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[C:27]([CH3:35])([CH3:34])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1.[C:37]([OH:40])(=[O:39])[CH3:38].C(Cl)CCl.C1C=CC2N(O)N=[N:51][C:49]=2C=1.[CH2:55](N(CC)CC)C>C1COCC1>[C:37]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:36])[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[C:27]([CH3:34])([CH3:35])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)(=[O:39])[CH3:38].[C:37]([NH:51][CH2:49][C:7]1([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:17])[F:18])[CH:13]=[CH:12][N:11]=2)[CH:6]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:36])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:55])=[O:32])[C:27]([CH3:35])([CH3:34])[CH2:26]3)=[N:22][CH:21]=2)[CH:4]=[CH:3][CH2:8]1)(=[O:40])[CH3:38]

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 58456138HCID 58456138、化合物

生成物 2

HCID 67256066HCID 67256066、化合物HCID 86673010HCID 86673010、化合物収率 184%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
23 °C

実験手順

A solution of (1S,4R)-4-{5-[3-(aminomethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (40 mg, 0.075 mmol) in anhydrous THF (5 ml) was added acetic acid (6.41 μl, 0.112 mmol, 1.5 equiv), EDC (21.48 mg, 0.112 mmol, 1.5 equiv), HOBt (17.16 mg, 0.112 mmol, 1.5 equiv) and then triethylamine (0.031 ml, 0.224 mmol, 3.0 equiv). The mixture was stirred at 23° C. for 14 h. The reaction mixture was partitioned between EtOAc (2×40 ml) and water (45 ml). The combined organic layers were dried over Na2SO4 and concentrated, affording the desired product, methyl (1S,4R)-4-[5-(5-[(acetylamino)methyl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 74%) as a yellow oil. 1H NMR (500 MHz, DMSO) δ 10.3 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.38 (m, 1H), 8.02 (bs, 1H), 7.90 (s, 1H), 7.68-7.66 (m, 2H), 7.52 (s, 1H), 7.28 (d, J=4.9 Hz, 1H), 5.94 (s, 1H), 4.24 (d, J=5.9 Hz, 2H), 4.12 (t, J=5.8 Hz, 1H), 3.60 (s, 3H), 3.31 (m, 2H), 1.97-1.88 (m, 5H), 1.75-1.73 (m, 2H), 1.24-1.22 (m, 6H).

後処理

  1. customThe reaction mixture was partitioned between EtOAc (2×40 ml) and water (45 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated

出典と根拠

ORDレコード
ord-2ac6c2051bde488f98b9e3fc2c95b5da
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

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