Formaldehyde → HCID 66918904, compound

HRID 2354163Notes

Reaction equation

HRID 2354163 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:38])=[C:11]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([N:24]5[CH2:29][C@@H:28]6[CH2:30][C@H:25]5[CH2:26][N:27]6[C:31](OC(C)(C)C)=O)[CH:20]=4)[N:15]=[CH:14]3)[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.C=O>C(O)=O.O.C(=O)(O)[O-].[Na+]>[CH:1]1([NH:4][C:5](=[O:6])[C:7]2[CH:8]=[CH:9][C:10]([CH3:38])=[C:11]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([N:24]5[CH2:29][C@@H:28]6[CH2:30][C@H:25]5[CH2:26][N:27]6[CH3:31])[CH:20]=4)[N:15]=[CH:14]3)[CH:12]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 712FormaldehydeHCID 66918841HCID 66918841, compound

Product 1

HCID 66918904HCID 66918904, compoundYield 54.8%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of tert-butyl(1S,4S)-5-(3-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-oxo-3,4-dihydroquinazolin-6-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.30 g) and 38% aqueous formaldehyde (0.42 ml) in formic acid (5 ml) was stirred at 90° C. for 16 hours. The reaction mixture was diluted with water and sodium bicarbonate added, evacuated to dryness. The residue was partitioned between methylene chloride and saturated NaHCO3 solution. The organic phase was washed with water and dried (magnesium sulphate). The residue was purified by column chromatography on an ion exchange column (isolute SCX-2 column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methylene chloride and then a 49:1 mixture of methanol and aqueous ammonia solution to give the title compound (0.137 g); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.70 (m, 2H), 1.96 (m, 1H), 2.14 (s, 3H), 2.32 (s, 3H), 2.57 (d, 1H), 2.87 (m, 2H), 3.29 (d, 1H), 3.45 (m, 1H), 3.56 (s, 1H), 4.50 (d, 1H), 7.13 (d, 1H), 7.26 (m, 1H), 7.52 (d, 1H), 7.61 (d, 1H), 7.81 (m, 1H), 7.90 (m, 1H), 7.99 (s, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 430.

Workup

  1. additionadded
  2. customevacuated to dryness
  3. customThe residue was partitioned between methylene chloride and saturated NaHCO3 solution
  4. washThe organic phase was washed with water
  5. dry with materialdried (magnesium sulphate)
  6. customThe residue was purified by column chromatography on an ion exchange column (isolute SCX-2 column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  7. additiona 49:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-5c73eccaae2c4187a0c186215d197cf1
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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