Formaldehyde → HCID 53630950, compound

HRID 2102468Notes

Reaction equation

HRID 2102468 reaction equation
[CH2:1]=O.[Cl:3][C:4]1[CH:5]=[C:6]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][C:26]4[N:30]=[C:29]([CH:31]5[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]5)[O:28][N:27]=4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[CH:7]=[CH:8][C:9]=1[Cl:10]>C(O)=O>[Cl:3][C:4]1[CH:5]=[C:6]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][C:26]4[N:30]=[C:29]([CH:31]5[CH2:36][CH2:35][N:34]([CH3:1])[CH2:33][CH2:32]5)[O:28][N:27]=4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[CH:7]=[CH:8][C:9]=1[Cl:10]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 53630951HCID 53630951, compound

Product 1

HCID 53630950HCID 53630950, compoundYield 69.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
95 °C

Procedure

Aqueous formaldehyde (37%, 894 ml, 12.0 mmol) was added to a solution of N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-4-yl-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine (1 g, 2.0 mmol) in formic acid (2 ml). The mixture was heated at 95° C. for two hours. The volatiles were removed under vacuum, the residue was dissolved in CH3OH and the pH of the solution was adjusted to 9 by addition of Biorad AG® 1-X8 hydroxide form resin. The solution was filtered, concentrated in vacuo and the residue was crystallized from MeOH/H2O to give N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-4-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine (714 mg; 69% yield). 1H NMR (400 MHz; DMSO-d6): 1.69-1.82 (m, 2H), 1.97-2.05 (m, 4H), 2.16 (s, 3H), 2.71-2.78 (m, 2H), 2.98-3.10 (m, 1H), 3.96 (s, 3H), 5.44 (s, 2H), 7.39 (s, 1H), 7.62 (d, 1H), 7.83 (s, 1H), 7.87 (dd, 1H), 8.22 (d, 1H), 8.53 (s, 1H), 9.63 (s, 1H); MS (EI) for C24H24Cl2N6O3: 515.07 (MH+)

Workup

  1. customThe volatiles were removed under vacuum
  2. dissolutionthe residue was dissolved in CH3OH
  3. additionthe pH of the solution was adjusted to 9 by addition of Biorad AG® 1-X8 hydroxide form resin
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customthe residue was crystallized from MeOH/H2O

Sources & evidence

ORD record
ord-4b6a6fc4310d4b899f62bd8ab70933b9
Source dataset
uspto-grants-2009_08
Patent number
US07576074B2

Reaction notes

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