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

HRID 1173026Notes

Reaction equation

HRID 1173026 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-efe4f08e0991467ebde83ab4f970e56c
Source dataset
uspto-grants-2010_11
Patent number
US07834013B2

Reaction notes

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