Acetic Acid → HCID 136248870, compound

HRID 922410Notes

Reaction equation

HRID 922410 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=3[O:25][CH3:26])[N:15]=2)[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=1.[CH3:29][C:30]([CH3:32])=O.C([O-])(=O)C.[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=3[O:25][CH3:26])[N:15]=2)[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH:30]([CH3:32])[CH3:29])[CH2:10][CH2:9]2)[CH:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 136248869HCID 136248869, compound

Product 1

HCID 136248870HCID 136248870, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 22134543HCID 22134543, compoundSolvent

Procedure

To a solution of 2-(3-chloro-5-(piperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (Example 31, 0.054 g, 0.14 mmol), acetone (0.060 g, 1.4 mmol), sodium acetate (0.023 g, 0.27 mmol), and acetic acid (0.16 g, 2.7 mmol) in 1,2-dichloroethane/methanol (5/5 mL) was added sodium triacetoxyborohydride (0.56 g, 2.7 mmol). The mixture was stirred at room temperature for 16 h and then concentrated. The residue was purified by silica gel chromatography eluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2. This material was further purified by reverse phase HPLC eluting with 10% to 90% CH3CN in H2O with 0.1% TFA. The product fractions were concentrated and the residue was dissolved in acetonitrile and water. The mixture was basified with concentrated NH4OH and concentrated. The residue was purified by reverse phase HPLC eluting with 10% to 90% CH3CN in H2O without TFA to afford the title compound (0.011 g, 18%) as an off-white solid: 1H NMR (500 MHz, CD3OD) δ 7.52 (s, 1H), 7.49 (d, J=1.5 Hz, 1H), 7.18 (t, J=1.5 Hz, 1H), 6.82 (d, J=2.5 Hz, 1H), 6.59 (d, J=2.5 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.35-3.60 (br s, 4H), 2.85-3.15 (br s, 4H), 1.25-1.40 (br s, 1H), 1.23 (d, J=6.5 Hz, 6H); ESI MS m/z 443 [M+H]+.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by silica gel chromatography
  3. washeluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
  4. customThis material was further purified by reverse phase HPLC
  5. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA
  6. concentrationThe product fractions were concentrated
  7. dissolutionthe residue was dissolved in acetonitrile
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC
  10. washeluting with 10% to 90% CH3CN in H2O without TFA

Sources & evidence

ORD record
ord-69b40557294345aebd94aca6cb29e7ab
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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