Formaldehyde → HCID 57979820, compound

HRID 1867679Notes

Reaction equation

HRID 1867679 reaction equation
[Cl:1][C:2]1[C:3]([F:30])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:28][CH3:29])=[C:16]([CH2:19][NH:20][CH:21]4[CH2:26][CH2:25][CH2:24][NH:23][C:22]4=[O:27])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.C=O.S([O-])([O-])(=O)=O.[Mg+2].[C:39]([BH3-])#N.[Na+]>CO>[Cl:1][C:2]1[C:3]([F:30])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:28][CH3:29])=[C:16]([CH2:19][N:20]([CH3:39])[CH:21]4[CH2:26][CH2:25][CH2:24][NH:23][C:22]4=[O:27])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 57979799HCID 57979799, compound

Product 1

HCID 57979820HCID 57979820, compoundYield 61.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)amino]piperidin-2-one (160 mg, 0.37 mmol prepared as described in Example 10), para-formaldehyde (112 mg, 3.72 mmol) and magnesium sulfate (90 mg, 0.74 mmol) were stirred in methanol (15 ml) and sodium cyanoborohydride (94 mg, 1.49 mmol) added. The mixture was heated at 50° C. for 1.5 hours, cooled, filtered and concentrated under reduced pressure. The resulting material was purified by flash chromatography on silica, eluting with increasingly polar mixtures of methanol/methylene chloride (2/98 to 5/95) to give the title product (101 mg, 61%) as a white solid; 1H NMR spectrum: (DMSO d6) 1.77 (m, 3H), 2.02 (m, 1H), 2.40 (s, 3H), 3.09 (m, 2H), 3.29 (dd, 1H), 3.95 (s, 5H), 7.18 (s, 1H), 7.28 (t, 1H), 7.40 (brs, 1H), 7.48 (t, 1H), 7.55 (m, 1H), 8.35 (s, 1H), 8.42 (s, 1H), 9.76 (s, 1H); Mass Spectrum: (M+H)+ 444.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting material was purified by flash chromatography on silica
  5. washeluting
  6. temperaturewith increasingly polar mixtures of methanol/methylene chloride (2/98 to 5/95)

Sources & evidence

ORD record
ord-b8b63a65ebcc40d18cc6b226dbb6eaa5
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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