p-Toluenesulfonic acid monohydrate → HCID 25015608, compound

HRID 2111420Notes

Reaction equation

HRID 2111420 reaction equation
[CH2:1]([N:4]1[CH2:10][CH:9]([CH3:11])[C:8](=[O:12])[N:7]([CH3:13])[C:6]2[CH:14]=[N:15][C:16](Cl)=[N:17][C:5]1=2)[CH:2]=[CH2:3].[NH2:19][C:20]1[CH:35]=[CH:34][C:23]([C:24]([NH:26][CH:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]2)=[O:25])=[CH:22][C:21]=1[O:36][CH3:37].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[CH2:1]([N:4]1[CH2:10][CH:9]([CH3:11])[C:8](=[O:12])[N:7]([CH3:13])[C:6]2[CH:14]=[N:15][C:16]([NH:19][C:20]3[CH:35]=[CH:34][C:23]([C:24]([NH:26][CH:27]4[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]4)=[O:25])=[CH:22][C:21]=3[O:36][CH3:37])=[N:17][C:5]1=2)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 87619625HCID 87619625, compound

Product 1

HCID 25015608HCID 25015608, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 0.050 g (0.00019 mole) of (rac)-9-allyl-2-chloro-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-65), 0.049 g (0.00019 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.047 g (0.00025 mole) of p-toluene-sulfonic acid monohydrate and 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 phases were extracted with dichloromethane. The combined organic phases were 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 0.047 g of (rac)-4-(9-allyl-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-65) as white solid. HRMS (ES+) m/z Calcd for C26H35N7O3+H [(M+H)+]: 494.2874. Found: 494.2878.

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 phases were extracted with dichloromethane
  5. washThe combined organic phases were 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-cd9377b747d7464582105970da4cbcb2
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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