Trifluoroacetic acid → HCID 24784975, compound

HRID 2243691Notes

Reaction equation

HRID 2243691 reaction equation
CC([CH2:5][N:6]([CH2:10][CH2:11][NH:12][C:13]1[N:14]=[C:15]([C:32]2[CH:37]=[C:36]([C:38]([NH:40][CH:41]([CH3:43])[CH3:42])=[O:39])[CH:35]=[CH:34][C:33]=2[CH3:44])[C:16]2[CH2:21][NH:20][C:19](=[O:22])[N:18]([C:23]3[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=3[F:30])[C:17]=2[N:31]=1)C(=O)[O-])(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[N:18]1[C:17]2[N:31]=[C:13]([NH:12][CH2:11][CH2:10][NH:6][CH3:5])[N:14]=[C:15]([C:32]3[CH:37]=[C:36]([CH:35]=[CH:34][C:33]=3[CH3:44])[C:38]([NH:40][CH:41]([CH3:42])[CH3:43])=[O:39])[C:16]=2[CH2:21][NH:20][C:19]1=[O:22]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86608560HCID 86608560, compound

Product 1

HCID 24784975HCID 24784975, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl(2-{[8-(2,6-difluorophenyl)-4-(2-methyl-5-{[(1-methylethyl)amino]carbonyl}phenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-2-yl]amino}ethyl)methylcarbamate (18 mg, 0.030 mmol) in DCM (5 mL) was added TFA (0.05 mL). The reaction mixture was stirred at room temperature overnight, quenched with triethylamine (0.2 mL) at −78° C. The residue was mixed with H2O (5.0 mL). The organic layer was separated and the aqueous layer was extracted with DCM (3×15 mL). The combined organic phases were washed with saturated aq. NaCl, dried over Na2SO4, filtered, and concentrated. Purification via a CombiFlash system (90% CH2Cl2/7% MeOH/3% NH4OH) then afforded the title compound (11 mg, 73%). LC-MS (ES) m/z 510 (M+H)+; 1H-NMR(MeOD) δ 1.27 (d, 6H), 2.26 (s, 3H), 2.30 (s, 3H), 2.56 (m, 2H), 3.22 (m, 2H), 4.11 (s, 2H), 4.23 (m, 1H), 7.15 (t, 2H), 7.46 (d, 1H), 7.52 (m, 1H), 7.69 (s, 1H), 7.85 (d, 1H).

Workup

  1. customquenched with triethylamine (0.2 mL) at −78° C
  2. additionThe residue was mixed with H2O (5.0 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with DCM (3×15 mL)
  5. washThe combined organic phases were washed with saturated aq. NaCl
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification via a CombiFlash system (90% CH2Cl2/7% MeOH/3% NH4OH)

Sources & evidence

ORD record
ord-8774c3f93a434e0f98645538ed07f7c1
Source dataset
uspto-grants-2010_03
Patent number
US07674789B2

Reaction notes

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