Trifluoroacetic acid → HCID 86732018, compound

HRID 527408Notes

Reaction equation

HRID 527408 reaction equation
C([C:5]1[C:10]([N:11]2[C:16]3[N:17]=[C:18]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([N:28]5[CH2:33][CH2:32][O:31][CH2:30][CH2:29]5)=[CH:24][C:23]=4[O:34][CH3:35])[N:19]=[CH:20][C:15]=3[CH:14]=[CH:13][C:12]2=[O:36])=[CH:9][CH:8]=[CH:7][C:6]=1[N:37](C1C=CC=C(N2C3N=C(NC4C=CC(N5CCOCC5)=CC=4OC)N=CC=3C=CC2=O)C=1C(C)(C)C)C(=O)[O-])(C)(C)C.[C:77]([OH:83])([C:79]([F:82])([F:81])[F:80])=[O:78]>C(Cl)Cl>[F:80][C:79]([F:82])([F:81])[C:77]([OH:83])=[O:78].[NH2:37][C:6]1[CH:5]=[C:10]([N:11]2[C:16]3[N:17]=[C:18]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([N:28]5[CH2:33][CH2:32][O:31][CH2:30][CH2:29]5)=[CH:24][C:23]=4[O:34][CH3:35])[N:19]=[CH:20][C:15]=3[CH:14]=[CH:13][C:12]2=[O:36])[CH:9]=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86732020HCID 86732020, compound

Product 1

HCID 86732018HCID 86732018, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude bis(tert-butyl (3-(2-((2-methoxy-4-morpholinophenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl))carbamate (2a) was treated with DCM (5 mL) and TFA (3 mL) and stirred at RT for 15 min. The reaction mixture was concentrated and purified on a Gilson preparatory HPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 u, 5-95% 0.1% TFA/CH3CN in 0.1% TFA/water) affording 8-(3-aminophenyl)-2-((2-methoxy-4-morpholinophenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one 2,2,2-trifluoroacetate (2b, 74 mg, 0.13 mmol, 41% yield) as a brown amorphous solid after drying in a genevac overnight. m/z (ESI, +ve ion) 446.1 (M+Na)+. 1H NMR (400 MHz, MeOH-d4) δ ppm 8.86 (1H, s), 8.05 (1H, d, J=9.6 Hz), 7.51-7.58 (1H, m), 7.32 (1H, dt, J=7.6, 1.3 Hz), 7.15-7.21 (2H, m), 6.90 (1H, d, J=8.6 Hz), 6.71 (1H, d, J=9.6 Hz), 6.67 (1H, d, J=2.5 Hz), 6.53 (1H, dd, J=8.7, 2.6 Hz), 3.87-3.93 (5H, m), 3.68 (3H, s), 3.18-3.24 (4H, m).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified on a Gilson preparatory HPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 u, 5-95% 0.1% TFA/CH3CN in 0.1% TFA/water)

Sources & evidence

ORD record
ord-55fa7ce3ee514e769c49d686143d7d67
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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