1,2-Dichloroethane → HCID 67257551, 화합물

HRID 1040161노트

반응식

HRID 1040161 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].[CH2:41](Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(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: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]([O:33][CH3:41])=[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: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 67257551HCID 67257551, 화합물수율 184.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

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-(3-[(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) 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-ec0e8a9e24574ddd9f2bc785f445b864
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

반응 노트

불러오는 중…