p-Toluenesulfonic acid monohydrate → HCID 57634997, compound

HRID 2111389Notes

Reaction equation

HRID 2111389 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][CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]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>[CH:16]1([CH2:15][N:7]2[CH2:8][CH:9]([CH3:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]5[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]5)=[O:28])=[CH:25][C:24]=4[O:39][CH3:40])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 87618406HCID 87618406, compound

Product 1

HCID 57634997HCID 57634997, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 0.050 g (0.00016 mole) of (rac)-2-chloro-9-cyclopentylmethyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-55), 0.050 g (0.00016 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.047 g (0.00016 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 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, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane-methanol (100:0-75:25) to give 0.048 g of (rac)-4-(9-cyclopentylmethyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diaze-pin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-55) as white powder. HRMS (ES+) m/z Calcd for C29H41N7O3+H [(M+H)+]: 536.3344. Found: 536.3344.

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. 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-2805597a8f3849feaad1e85174d5aca1
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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