2-Amino-5-(methylsulfanyl)benzoic acid → 3-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-6-(methylthio)-4(3H)-quinazolinone

HRID 2309535Notes

Reaction equation

HRID 2309535 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([S:11][CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[N:23]=[C:22]2[NH:30][CH:31]2[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][NH:39][CH:40]=O)[CH2:33][CH2:32]2)=[CH:16][CH:15]=1>>[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[N:23]=[C:22]2[NH:30][CH:31]2[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][N:39]3[C:4](=[O:6])[C:3]4[C:2](=[CH:10][CH:9]=[C:8]([S:11][CH3:12])[CH:7]=4)[N:1]=[CH:40]3)[CH2:33][CH2:32]2)=[CH:16][CH:15]=1

Participants

3

Reactant 2

HCID 127132522-Amino-5-(methylsulfanyl)benzoic acidHCID 13653885N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]formamide

Product 1

HCID 139831233-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-6-(methylthio)-4(3H)-quinazolinoneYield 41.5%

Procedure

A mixture of 3.7 parts of 2-amino-5-(methylthio)benzoic acid and 8.9 parts of N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]formamide was stirred for 5 hours at 150°-160° C. The whole was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 1,1'-oxybisethane and acetonitrile. The product was filtered off and dried, yielding 4.5 parts (41.5%) of 3-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-6-(methylthio)-4(3H)-quinazolinone; mp. 101.4° C. (compound 138).

Workup

  1. customThe whole was purified by column chromatography over silica gel using
  2. additiona mixture of trichloromethane and methanol
  3. customThe pure fractions were collected
  4. customthe eluent was evaporated
  5. customThe residue was crystallized from a mixture of 1,1'-oxybisethane and acetonitrile
  6. filtrationThe product was filtered off
  7. customdried

Sources & evidence

ORD record
ord-b9814eff9a5f4eb2a64299b5908075e5
Source dataset
uspto-grants-1987_09
Patent number
US04695569

Reaction notes

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