Diisopropylethylamine → HCID 44610865, compound

HRID 1897698Notes

Reaction equation

HRID 1897698 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.C(OC([N:37]([CH2:44][CH3:45])[C:38]1([C:41](O)=[O:42])[CH2:40][CH2:39]1)=O)(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[C:10]([F:22])=[CH:11][C:12]([CH:16]3[CH2:17][CH2:18][N:19]([C:41]([C:38]4([NH:37][CH2:44][CH3:45])[CH2:40][CH2:39]4)=[O:42])[CH2:20][CH2:21]3)=[C:13]([CH3:15])[CH:14]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 446126165-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamineHCID 57238924HCID 57238924, compound

Product 1

HCID 44610865HCID 44610865, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (67.3 mg, 0.17 mmol), 1-(tert-butoxycarbonyl(ethyl)amino)cyclopropanecarboxylic acid (38.0 mg, 0.17 mmol), HATU (63.0 mg, 0.17 mmol) and diisopropylethylamine (57 μL, 0.34 mmol) in 1 mL of DMF was stirred at room temperature overnight. The reaction mixture was partitioned between EtOAc and water, the combined organic extracts were dried (Na2SO4) and then concentrated in vacuo. The resulting crude mixture was dissolved in 5 mL of DCM and 4 mL of TFA and was then stirred for 2 h followed by concentration in vacuo. The crude product was purified by RP-HPLC to afford (4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-5-fluoro-2-methylphenyl)piperidin-1-yl)(1-(ethylamino)cyclopropyl)methanone; ESMS m/z 527.2 (M+H+).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. dry with materialthe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting crude mixture was dissolved in 5 mL of DCM
  5. stirring4 mL of TFA and was then stirred for 2 h
  6. concentrationfollowed by concentration in vacuo
  7. customThe crude product was purified by RP-HPLC

Sources & evidence

ORD record
ord-583d9e21447649fdad125cce746219ce
Source dataset
uspto-grants-2013_08
Patent number
US08519129B2

Reaction notes

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