Diisopropylethylamine → N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}cyclopropane-1,1-dicarboxamide

HRID 1040075Notes

Reaction equation

HRID 1040075 reaction equation
[C:1]([C:4]1([C:7]([OH:9])=O)[CH2:6][CH2:5]1)(=[O:3])[NH2:2].[NH2:10][C:11]([CH:38]1[CH2:40][CH2:39]1)([CH:35]1[CH2:37][CH2:36]1)[C:12]1[S:13][C:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25]3[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=3)[CH:20]=[C:21]([CH3:23])[CH:22]=2)=[CH:15][N:16]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[CH:38]1([C:11]([CH:35]2[CH2:36][CH2:37]2)([C:12]2[S:13][C:14]([C:17]3[CH:18]=[C:19]([NH:24][C:25]4[N:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:28]=[CH:27][N:26]=4)[CH:20]=[C:21]([CH3:23])[CH:22]=3)=[CH:15][N:16]=2)[NH:10][C:7]([C:4]2([C:1]([NH2:2])=[O:3])[CH2:6][CH2:5]2)=[O:9])[CH2:39][CH2:40]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27332721-(Aminocarbonyl)-1-cyclopropanecarboxylic acidHCID 58456217N-(3-{2-[amino(dicyclopropyl)methyl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)-pyrimidin-2-amine

Product 1

HCID 67433438N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}cyclopropane-1,1-dicarboxamideYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with 1-carbamoylcyclopropanecarboxylic acid (16.23 mg, 0.126 mmol), N-(3-{2-[amino(dicyclopropyl)methyl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)-pyrimidin-2-amine (56 mg, 0.126 mmol), BOP (83 mg, 0.189 mmol), DIPEA (43.9 μL, 0.251 mmol) and DMF (10 mL). The reaction was stirred at room temperature for 90 minutes. The mixture was diluted with ethyl acetate, washed with saturated NaHCO3, followed by brine, dried (Na2SO4), filtered, and concentrated to afford N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}cyclopropane-1,1-dicarboxamide (67.6 mg, 0.121 mmol, 97% yield) as an off white solid. MS ESI: [M+H]+ m/z 557.1. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 9.81 (s, 1H), 8.83 (d, 1H), 8.01 (s, 1H), 7.91 (s, 1H), 7.44 (s, 1H), 7.29 (m, 3H), 7.15 (s, 1H), 2.31 (s, 3H), 1.67-1.46 (m, 2H), 1.28-1.20 (m, 4H), 0.7-0.65 (m, 2H), 0.56-0.54 (m, 2H), 0.44-0.38 (m, 4H). rhSYK activity=+++

Workup

  1. washwashed with saturated NaHCO3
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-793afc159d044414986dcf291da297f7
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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