p-Toluenesulfonic acid monohydrate → HCID 57635076, compound

HRID 2111362Notes

Reaction equation

HRID 2111362 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][O:18][CH2:17][CH2:16]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:39][CH3:40].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]([CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:6]2[N:21]=[C:2]([NH:22][C:23]3[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]4[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]4)=[O:28])=[CH:25][C:24]=3[O:39][CH3:40])[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 87555943HCID 87555943, compound

Product 1

HCID 57635076HCID 57635076, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 0.050 g (0.00016 mole) of (rac)-2-chloro-5,7-dimethyl-9-(tetrahydropyran-4-yl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-45), 0.042 g (0.00016 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.047 g (0.00024 mole) of p-toluenesulfonic 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 and the residue diluted with dichloromethane, 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 and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane-methanol (100:0-75:25) to give 0.0483 g of (rac)-4-(5,7-dimethyl-6-oxo-9-(tetrahydro-pyran-4-yl)-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-45) as a white powder. HRMS (ES+) m/z Calcd for C28H39N7O4+H [(M+H)+]: 538.3137. Found: 538.3136.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue 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. 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-54f6d866217b48deab5d778581608d31
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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