Diisopropylethylamine → N-(4-chloro-2-(6-((3-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)phenyl)-3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamide

HRID 625386Notes

Reaction equation

HRID 625386 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)[CH:10]=1.[CH2:27]([N:29]([CH2:44][CH3:45])[CH2:30][CH2:31][N:32]([CH2:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38](O)=[O:39])[CH3:33])[CH3:28].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:38](=[O:39])[C:37]2[CH:41]=[CH:42][CH:43]=[C:35]([CH2:34][N:32]([CH2:31][CH2:30][N:29]([CH2:44][CH3:45])[CH2:27][CH3:28])[CH3:33])[CH:36]=2)=[C:3]([C:9]2[CH:10]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:25])([F:24])[F:26])[CH:18]=3)[N:12]=[CH:13][N:14]=2)[CH:4]=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 665866436-(2-amino-5-chlorophenyl)-N-(3-(trifluoromethyl)benzyl)pyrimidin-4-amineHCID 665868393-(((2-(Diethylamino)ethyl)(methyl)amino)methyl)benzoic acid

Product 1

HCID 69631937N-(4-chloro-2-(6-((3-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)phenyl)-3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamideYield 11.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of 6-(2-amino-5-chlorophenyl)-N-(3-(trifluoromethyl)benzyl)pyrimidin-4-amine 65b (200 mg, 0.53 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (130 mg, 0.49 mmol, 1.00 equiv), HATU (300 mg, 0.79 mmol, 1.50 equiv), and N,N-diisopropylethylamine (270 mg, 2.09 mmol, 5.00 equiv). The resulting solution was stirred for 2 days at 25° C. in an oil bath. The reaction was then quenched with 50 mL of water. The resulting solution was extracted with 2×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×50 mL of saturated NH4Cl, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 36.1 mg (9%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 8.73 (s, 1H), 8.60 (d, J=9.3 Hz, 1H), 8.41 (s, 1H), 8.19 (m, 1H), 7.92 (m, 3H), 7.64 (m, 7H), 7.14 (s, 1H), 4.73 (d, J=5.7 Hz, 2H), 3.35 (s, 2H), 3.14 (d, J=6.9 Hz, 4H), 1.18 (t, J=7.2 Hz, 6H). MS (ES, m/z): 625 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. customThe reaction was then quenched with 50 mL of water
  3. extractionThe resulting solution was extracted with 2×100 mL of ethyl acetate
  4. washThe resulting mixture was washed with 2×50 mL of saturated NH4Cl
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product (200 mg) was purified by reverse phase HPLC
  8. washeluting with a water/CH3CN gradient
  9. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-71bf021cc4e842979e28d0f1132d95da
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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