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 410585Notes

Reaction equation

HRID 410585 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. customdried
  3. filtration(Na2SO4), filtered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-46a0bac8776446cfb6fbd951c24a7539
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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