p-Toluenesulfonic acid monohydrate → HCID 57635000, compound

HRID 2111346Notes

Reaction equation

HRID 2111346 reaction equation
[CH2:1]([N:8]1[CH2:14][CH:13]([CH3:15])[C:12](=[O:16])[N:11]([CH3:17])[C:10]2[CH:18]=[N:19][C:20](Cl)=[N:21][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:23][C:24]1[CH:39]=[CH:38][C:27]([C:28]([NH:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[O:29])=[CH:26][C:25]=1[O:40][CH3:41].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[CH2:1]([N:8]1[CH2:14][CH:13]([CH3:15])[C:12](=[O:16])[N:11]([CH3:17])[C:10]2[CH:18]=[N:19][C:20]([NH:23][C:24]3[CH:39]=[CH:38][C:27]([C:28]([NH:30][CH:31]4[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]4)=[O:29])=[CH:26][C:25]=3[O:40][CH3:41])=[N:21][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 87619633HCID 87619633, compound

Product 1

HCID 57635000HCID 57635000, compoundYield 51.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 0.050 g (0.00016 mole) of (rac)-9-benzyl-2-chloro-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-42), 0.042 g (0.00016 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.046 g (0.00024 mole) of p-toluenesulfonic acid monohydrate in 4.0 mL of 2-propanol was heated at 180 degrees 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 and the combined organic phases washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane-methanol (100:0-75:25) to give 0.0451 g of (rac)-4-(9-benzyl-5,7-dimethyl-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-42) as white powder. HRMS (ES+) m/z Calcd for C30H37N7O3+H [(M+H)+]: 544.3031. Found: 544.3031.

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 washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with dichloromethane-methanol (100:0-75:25)

Sources & evidence

ORD record
ord-2233fb1b838b4c90becd462536a1caa8
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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