Trifluoroacetic acid → 8-(3-aminophenyl)-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 527406Notes

Reaction equation

HRID 527406 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:16][C:17]1[N:18]=[CH:19][C:20]2[CH:26]=[CH:25][C:24](=[O:27])[N:23]([C:28]3[CH:29]=[C:30]([NH:34]C(=O)OC(C)(C)C)[CH:31]=[CH:32][CH:33]=3)[C:21]=2[N:22]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:34][C:30]1[CH:29]=[C:28]([N:23]2[C:21]3[N:22]=[C:17]([NH:16][C:4]4[CH:5]=[CH:6][C:7]([N:9]5[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]5)=[CH:8][C:3]=4[O:2][CH3:1])[N:18]=[CH:19][C:20]=3[CH:26]=[CH:25][C:24]2=[O:27])[CH:33]=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86732016tert-butyl (3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

Product 1

HCID 867320178-(3-aminophenyl)-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude 1a from above was treated with DCM (20 mL) and TFA (20 mL) and stirred at RT for 30 min. The reaction mixture was concentrated under reduced pressure (rotary evaporator) and purified on a silica gel column (1-20% 2M NH3/MeOH in DCM) affording 8-(3-aminophenyl)-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (1b) (470 mg, 1.03 mmol, 79% yield) as a brown amorphous solid. m/z (ESI, +ve ion) 458.0 (M+H)+. 1H NMR (400 MHz, MeOH-d4) δ ppm 8.67 (1H, s), 7.88 (1H, d, J=9.4 Hz), 7.63 (1H, d, J=8.2 Hz), 7.32 (1H, t, J=8.0 Hz), 6.91 (1H, dd, J=8.1, 1.5 Hz), 6.59-6.65 (2H, m), 6.53-6.59 (1H, m), 6.46-6.52 (1H, m), 6.24 (1H, br. s.), 3.88 (3H, s), 3.21 (4H, br. s.), 2.84 (4H, br. s.), 2.53 (3H, s).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure (rotary evaporator)
  2. custompurified on a silica gel column (1-20% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-e21867c83cec4a1c8a772d807bfbdfe4
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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