4-Mercaptobenzoic acid → 4-(9-cyclopentyl-6,7,8,9-tetrahydro-5,7,7-trimethyl-6-oxo-5H-pyrimido[4,5-b][1,4]diazepin-2-ylthio)-benzoic acid

HRID 1945141Notes

Reaction equation

HRID 1945141 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([CH3:15])([CH3:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[SH:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=1>C(#N)C>[CH:16]1([N:7]2[CH2:8][C:9]([CH3:15])([CH3:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([S:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=4)=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

4

Reactant 2

HCID 957384-Mercaptobenzoic acid2×HCID 592951162-Chloro-9-cyclopentyl-5,7,7-trimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Product 1

HCID 579405234-(9-cyclopentyl-6,7,8,9-tetrahydro-5,7,7-trimethyl-6-oxo-5H-pyrimido[4,5-b][1,4]diazepin-2-ylthio)-benzoic acidYield 27%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2-Chloro-9-cyclopentyl-8,9-dihydro-5,7,7-trimethyl-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (100 mg, 0.324 mmol) and 4-mercaptobenzoic acid (50 mg, 0.324 mmol) in acetonitrile (5 mL) was heated under reflux for 4 hours. Additional 4-mercaptobenzoic acid (50 mg, 0.324 mmol) was added and the reaction mixture was heated under reflux for 16 hours. After cooling, the crude reaction mixture was filtered through Celite and washed with acetonitrile. The crude product was purified by column chromatography (0%-10% MeOH:CH2Cl2) and triturated with MeOH to give the title compound (37 mg, 27% yield) as a white solid. NMR DMSO D6 1.03 (6H, s), 1.20-1.38 (6H, m), 1.42-1.53 (2H, m), 3.17 (3H, s), 3.27 (2H, s), 4.47 (1H, dt), 7.72 (2H, dd), 7.99 (2H, dd), 8.02 (1H, s); MS (ES+) 427, (ES−) 425.

Workup

  1. temperatureunder reflux for 4 hours
  2. temperaturethe reaction mixture was heated
  3. temperatureunder reflux for 16 hours
  4. temperatureAfter cooling
  5. customthe crude reaction mixture
  6. filtrationwas filtered through Celite
  7. washwashed with acetonitrile
  8. customThe crude product was purified by column chromatography (0%-10% MeOH:CH2Cl2)
  9. customtriturated with MeOH

Sources & evidence

ORD record
ord-5aad1e42ce574a26b97a59fedbb22b97
Source dataset
uspto-grants-2013_03
Patent number
US08394952B2

Reaction notes

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