Formaldehyde → HCID 16062917, compound

HRID 1817703Notes

Reaction equation

HRID 1817703 reaction equation
C(O[C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[N:16][C:17]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[N:18][C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[CH2:34]=O>C(O)=O.O.[OH-].[Na+]>[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C:17]2[N:16]=[C:15]([C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)[C:12]3[CH2:13][CH2:14][N:8]([CH3:6])[CH2:9][C:10](=[CH2:34])[C:11]=3[N:18]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 2

HCID 712FormaldehydeHCID 66616339HCID 66616339, compound

Product 1

HCID 16062917HCID 16062917, compound

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-(4-fluoro-benzyl)-4-(4-fluoro-phenyl)-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepine-7-carboxylic acid tert-butyl ester in formic acid was added paraformaldehyde (10 equiv.). The mixture was heated at 80° C. for 6 h. The mixture was diluted with water and basified to pH ˜10 with 1 M NaOH. The mixture was extracted with CH2Cl2, dried and concentrated. Chromatography on SiO2 (0-5% 2 M NH3 in MeOH/CH2Cl2) afforded the desired compound. 2-(4-Fluoro-benzyl)-4-(4-fluoro-phenyl)-7-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine was also obtained. MS (ESI): exact mass calcd. for C23H21F2N3, 377.17; m/z found, 378.4 [M+H]+. 1H NMR (CDCl3): 7.50-7.46 (m, 2H), 7.42-7.37 (m, 2H), 7.17-7.12 (m, 2H), 6.99-6.94 (m, 4H), 6.03-6.01 (m, 1H), 5.47-5.46 (m, 1H), 4.25 (s, 2H), 3.51 (s, 2H), 2.87-2.83 (m, 2H), 2.76-2.72 (m, 2H), 2.41 (s, 3H).

Workup

  1. extractionThe mixture was extracted with CH2Cl2
  2. customdried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-df9391a187344856a59898c6fa6c4ca2
Source dataset
uspto-grants-2009_10
Patent number
US07598255B2

Reaction notes

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