Disodium disulfite → 6-fluoro-8-methyl-2-[4-(4-methyl-piperazin-1-yl)-phenyl]-3H-quinazolin-4-one

HRID 1050963Notes

Reaction equation

HRID 1050963 reaction equation
[NH2:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=2)[CH2:16][CH2:15]1.S(OS([O-])=O)([O-])=O.[Na+].[Na+]>CN1CCCC1=O>[F:12][C:8]1[CH:7]=[C:3]2[C:2](=[C:10]([CH3:11])[CH:9]=1)[N:1]=[C:24]([C:23]1[CH:22]=[CH:21][C:20]([N:17]3[CH2:16][CH2:15][N:14]([CH3:13])[CH2:19][CH2:18]3)=[CH:27][CH:26]=1)[NH:6][C:4]2=[O:5]

Participants

5

Reactant 3

HCID 24346Disodium disulfiteHCID 7365334-(4-Methylpiperazin-1-yl)benzaldehydeHCID 68276549HCID 68276549, compound

Product 1

HCID 1362370046-fluoro-8-methyl-2-[4-(4-methyl-piperazin-1-yl)-phenyl]-3H-quinazolin-4-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 2-amino-5-fluoro-3-methyl-benzamide (84.1 mg, 0.50 mmol), 4-(4-methyl-piperazin-1-yl)-benzaldehyde (123 mg, 0.60 mmol) and sodium disulfite (97 mg, 0.51 mmol) in N-methyl-pyrrolidone (1 ml) is heated to 150° C. and stirred at this temperature for 16 hours. The reaction mixture is allowed to reach room temperature and poured into ice water. The resulting precipitate is collected by filtration, washed with water and dried. The residue is chromatographed on a silica gel column with methanol/dichloromethane as eluent to afford 6-fluoro-8-methyl-2-[4-(4-methyl-piperazin-1-yl)-phenyl]-3H-quinazolin-4-one as brown powder; HPLC/MS 1.47 min (A), [M+H] 353; 1H NMR (400 MHz, DMSO-d6) δ [ppm] 12.34 (s, 1H), 8.69-7.90 (m, 2H), 7.86-7.26 (m, 2H), 7.28-6.73 (m, 2H), 3.33-3.27 (m, 4H), 2.61 (s, 3H), 2.45 (t, J=5.1 Hz, 4H), 2.23 (s, 3H).

Workup

  1. customto reach room temperature
  2. filtrationThe resulting precipitate is collected by filtration
  3. washwashed with water
  4. customdried
  5. customThe residue is chromatographed on a silica gel column with methanol/dichloromethane as eluent

Sources & evidence

ORD record
ord-abafbaa13b2c43bc8b750ee31bf4775a
Source dataset
uspto-grants-2016_07
Patent number
US09388142B2

Reaction notes

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