Potassium Phosphate, Tribasic → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyrimidin-4-yl)-3-(trifluoromethyl)phenyl)acetamide

HRID 1036261Notes

Reaction equation

HRID 1036261 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:38])[CH2:18][C:19]3[CH:24]=[CH:23][C:22](B4OC(C)(C)C(C)(C)O4)=[C:21]([C:34]([F:37])([F:36])[F:35])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].Cl[C:40]1[CH:45]=[CH:44][N:43]=[C:42]([CH3:46])[N:41]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>>[C:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:38])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:40]4[CH:45]=[CH:44][N:43]=[C:42]([CH3:46])[N:41]=4)=[C:21]([C:34]([F:36])([F:35])[F:37])[CH:20]=3)=[N:14][CH:15]=2)[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4244474-Chloro-2-methylpyrimidineHCID 58447853N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)phenyl)acetamide

Product 1

HCID 58447882N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyrimidin-4-yl)-3-(trifluoromethyl)phenyl)acetamide

Conditions

Temperature
100 °C

Procedure

A mixture of N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)phenyl)acetamide 192-3 (53 mg, 0.1 mmol), 4-chloro-2-methylpyrimidine 192-4 (18 mg, 0.14 mmol) Pd(PPh3)4 (11 mg, 0.01 mmol) and K3PO4 (42 mg, 0.2 mmol) in dioaxane (1.0 mL) was flushed with nitrogen and heated to 100° C. for 2 hours. The salt was removed by filtration and the filtrate was taken to dryness by rotary evaporation. The residue was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-(2-methylpyrimidin-4-yl)-3-(trifluoromethyl)phenyl)acetamide 192. MS m/z 499.2 (M+1). 1H NMR 400 MHz (DMSO-d6) δ10.58 (s, 1H), 8.77 (d, 1H), 8.02 (s, 1H), 7.89 (m, 2H), 7.73 (d, 1H), 7.54 (d, 1H), 7.42 (m, 2H), 3.76 (s, 2H), 3.66 (b, 4H), 3.14 (b, 2H), 3.07 (b, 2H), 2.64 (s, 3H), 2.03 (s, 3H).

Workup

  1. customwas flushed with nitrogen
  2. customThe salt was removed by filtration
  3. customthe filtrate was taken to dryness by rotary evaporation
  4. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-50dcb878d0294c0b993a73fa278d12c6
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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