p-Toluenesulfonic acid monohydrate → HCID 57635008, compound

HRID 2111324Notes

Reaction equation

HRID 2111324 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]([CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C:6]=2[N:20]=1.[NH2:21][C:22]1[CH:37]=[CH:36][C:25]([C:26]([NH:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:27])=[CH:24][C:23]=1[O:38][CH3:39].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[CH3:12][N:11]1[C:10](=[O:13])[CH:9]([CH3:14])[CH2:8][N:7]([CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C:6]2[N:20]=[C:2]([NH:21][C:22]3[CH:37]=[CH:36][C:25]([C:26]([NH:28][CH:29]4[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]4)=[O:27])=[CH:24][C:23]=3[O:38][CH3:39])[N:3]=[CH:4][C:5]1=2

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 87617679HCID 87617679, compound

Product 1

HCID 57635008HCID 57635008, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 0.05 g, (0.00017 mole) of (rac)-2-chloro-5,7-dimethyl-9-(3-methyl-butyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-27), 0.044 g, (0.00017 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.049 g, (0.00026 mole) of p-toluenesulfonic acid monohydrate and 4 mL of 2-propanol was heated at 180 degree for 2 hours 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. The combined organic phase was 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 (100:0-75:25) to give 0.049 g of (rac)-4-[5,7-dimethyl-9-(3-methyl-butyl)-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-27). HRMS (ES+) m/z Calcd for C28H41N7O2+H [(M+H)+]: 524.3344. Found: 524.3342.

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 phase was 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 (100:0-75:25)

Sources & evidence

ORD record
ord-943715a7966442b89ee8eb7914238763
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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