p-Toluenesulfonic acid monohydrate → HCID 68904178, compound

HRID 2111421Notes

Reaction equation

HRID 2111421 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([CH3:14])[CH2:8][N:7]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:21]=1.[CH3:22][O:23][C:24](=[O:34])[C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[C:27]([O:32][CH3:33])[CH:26]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[CH3:22][O:23][C:24](=[O:34])[C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:2]2[N:3]=[CH:4][C:5]3[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([CH3:14])[CH2:8][N:7]([CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]4)[C:6]=3[N:21]=2)=[C:27]([O:32][CH3:33])[CH:26]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 602411Methyl 4-amino-3-methoxybenzoateHCID 87555255HCID 87555255, compound

Product 1

HCID 68904178HCID 68904178, compoundYield 96.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 0.10 g (0.00032 mole) of (rac)-2-chloro-9-cyclohexyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-19), 0.060 g (0.00032 mole) of 4-amino-3-methoxy-benzoic acid methyl ester, 0.10 g (0.00049 mole) of p-toluene-sulfonic acid monohydrate and 4 mL of 2-propanol at 150 degrees for 1 hour in a microwave reactor. The reaction mixture was concentrated under reduced pressure. The residue was diluted with dichloromethane and washed twice with saturated sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane and the combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (100:0-85:15%), to give 0.14 g of (rac)-4-(9-cyclohexyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid methyl ester as white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionThe residue was diluted with dichloromethane
  3. washwashed twice with saturated sodium bicarbonate solution
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with dichloromethane-methanol (100:0-85:15%)

Sources & evidence

ORD record
ord-7dbcc399e1cb41888db3d3472c185025
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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