Acetic Acid → HCID 86658256, 화합물

HRID 410661노트

반응식

HRID 410661 반응식
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[C:27]([CH3:36])([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:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1.[O-:38][C:39]#[N:40].[K+].C(O)(=O)C.O>C1COCC1>[C:39]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[C:27]([CH3:35])([CH3:36])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:17])([F:19])[F:18])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)(=[O:38])[NH2:40].[C:39]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[C:27]([CH3:35])([CH3:36])[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:38])[NH2:40]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 962WaterHCID 11378442Potassium cyanateHCID 67432750HCID 67432750, 화합물

생성물 2

HCID 67430374HCID 67430374, 화합물HCID 86658256HCID 86658256, 화합물수율 184.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

To a solution of methyl (1S,4R)-4-{5-[3-(aminomethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 0.075 mmol) in anhydrous THF (1.5 ml) was added potassium cyanate (12.12 mg, 0.149 mmol, 2.0 equiv), acetic acid (8.55 μl, 0.149 mmol, 2.0 equiv), and water (4.5 ml). The mixture was stirred at 50° C. for 14 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with EtOAc (40 ml). The organic layer were dried over Na2SO4, filtered and concentrated to provide the desired product, methyl (1S,4R)-4-[5-(3-[(carbamoylamino)methyl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 88%), as an orange oil. MS ESI: [M+H]+ m/z 579.2. 1H NMR (500 MHz, DMSO) δ 10.3 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.03 (bs, 1H), 7.88 (s, 1H), 7.50 (s, 1H), 7.28 (d, 1H, J=4.9 Hz), 7.17 (s, 1H), 6.46 (m, 1H), 5.55 (s, 2H), 4.16 (m, 2H), 3.59 (s, 3H), 2.31 (m, 1H), 1.87-1.84 (m, 4H), 1.75-1.73 (m, 2H), 1.17 (s, 3H), 0.96 (s, 3H).

후처리

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. extractionextracted with EtOAc (40 ml)
  3. dry with materialThe organic layer were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fd019452a26e44b0ab48b054dc4282f2
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

반응 노트

불러오는 중…