1,2-Dichloroethane → HCID 86673010, 화합물

HRID 410662노트

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HRID 410662 반응식
[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]

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 58456138HCID 58456138, 화합물

생성물 2

HCID 67256066HCID 67256066, 화합물HCID 86673010HCID 86673010, 화합물수율 184%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
23 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2ac6c2051bde488f98b9e3fc2c95b5da
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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