p-Toluenesulfonic acid → methyl4-[(9-cyclopentyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoate

HRID 2234350Notes

Reaction equation

HRID 2234350 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1.[CH3:20][O:21][C:22](=[O:32])[C:23]1[CH:28]=[CH:27][C:26]([NH2:29])=[C:25]([O:30][CH3:31])[CH:24]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C>[CH3:20][O:21][C:22](=[O:32])[C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:2]2[N:3]=[CH:4][C:5]3[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][CH2:8][N:7]([CH:14]4[CH2:18][CH2:17][CH2:16][CH2:15]4)[C:6]=3[N:19]=2)=[C:25]([O:30][CH3:31])[CH:24]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 602411Methyl 4-amino-3-methoxybenzoateHCID 579405262-Chloro-9-cyclopentyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one2×

Product 1

HCID 68682079methyl4-[(9-cyclopentyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoateYield 38.3%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

2-Chloro-9-cyclopentyl-5-methyl-5,7,8,9-tetrahydro-6H-pyrimido[4,5-b][1,4]diazepin-6-one (Intermediate 1; 500 mg, 1.78 mmol), methyl4-amino-3-methoxybenzoate (324 mg, 1.78 mmol) and p-toluenesulfonic acid (847 mg, 4.45 mmol) were suspended in (2R/S)-4-methyl-2-pentanol (10 mL) and heated at reflux for 5 h. The reaction mixture was cooled and loaded onto an SCX-2 column and washed with MeOH (20 mL). The crude product was then eluted from the SCX-2 column with NH3 (40 mL, 7M in MeOH) and the volatiles removed under reduced pressure. Purification by column chromatography (SiO2, eluent gradient 0-10% MeOH in DCM) afforded the title compound (290 mg, 38%) as a solid.

Workup

  1. temperatureheated
  2. temperatureat reflux for 5 h
  3. temperatureThe reaction mixture was cooled
  4. washwashed with MeOH (20 mL)
  5. washThe crude product was then eluted from the SCX-2 column with NH3 (40 mL, 7M in MeOH)
  6. customthe volatiles removed under reduced pressure
  7. customPurification by column chromatography (SiO2, eluent gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-ed8fc8c30e654659aa32a767b2c1cbbc
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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