Cyclobutylamine → (trans)-N-cyclobutyl-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxamide

HRID 1173026

반응식

HRID 1173026 반응식
CN(C(ON1N=[N:16][C:11]2[CH:12]=[CH:13][CH:14]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1[N:27]=[C:28]([C:45]2[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][CH:46]=2)[S:29][C:30]=1[CH2:31][NH:32][C:33]1[CH:38]=[CH:37][C:36]([C@@H:39]2[CH2:41][C@H:40]2[C:42](O)=[O:43])=[CH:35][CH:34]=1.C1(N)CCC1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH:11]1([NH:16][C:42]([C@@H:40]2[CH2:41][C@H:39]2[C:36]2[CH:37]=[CH:38][C:33]([NH:32][CH2:31][C:30]3[S:29][C:28]([C:45]4[CH:50]=[CH:49][C:48]([C:51]([F:52])([F:54])[F:53])=[CH:47][CH:46]=4)=[N:27][C:26]=3[CH3:25])=[CH:34][CH:35]=2)=[O:43])[CH2:12][CH2:13][CH2:14]1

참가 물질

6

반응물 4

HCID 75645CyclobutylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11487291(+)-(trans)-2-{4-[({4-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxylic acid

생성물 1

HCID 11237091(trans)-N-cyclobutyl-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxamide수율 77.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

HATU (0.154 g, 0.41 mmol) and (+)-(trans)-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]phenyl}cyclopropanecarboxylic acid (III-3c) (0.135 g, 0.31 mmol) in DMF (10 mL) were stirred at RT for 15 min, then cyclobutylamine (0.50 g) was added. The solution was stirred at RT for 1 h, then saturated NaHCO3 solution (20 mL) was added. The resulting solid was filtered, washed with water (10 mL) and dissolved in ethyl acetate (50 mL). The organic layer was dried over MgSO4, filtered and concentrated to give the title compound as a white powder (0.116 g, 77%). 1H NMR (400 MHz, DMSO) δ8.23 (d, J=7.5 Hz, 1H), 8.01 (d, J=8.1 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H), 6.81 (d, J=8.3 Hz, 2H), 6.51 (d, J=8.4 Hz, 2H), 6.20 (t, J=5.8 Hz, 1H), 4.38 (d, J=5.5 Hz, 2H), 4.19-4.13 (m, 1H), 2.42 (s, 3H), 2.10-2.06 (m, 2H), 2.04-1.99 (m, 1H), 1.85-1.75 (m, 2H), 1.59-1.50 (m, 3H), 1.18-1.13 (m, 1H), 1.01-0.96 (m, 1H).

후처리

  1. filtrationThe resulting solid was filtered
  2. washwashed with water (10 mL)
  3. dissolutiondissolved in ethyl acetate (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-efe4f08e0991467ebde83ab4f970e56c
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834013B2

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