p-Toluenesulfonic acid monohydrate → 4-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 1676669

Reaction equation

HRID 1676669 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[C:9]([F:14])([F:13])[CH2:8][N:7]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[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][CH:23]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[CH:15]1([N:7]2[CH2:8][C:9]([F:14])([F:13])[C:10](=[O:12])[NH:11][C:5]3[CH:4]=[N:3][C:2]([NH:21][C:22]4[CH:23]=[CH:24][C:25]([C:26]([NH:28][CH:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)=[O:27])=[CH:36][CH:37]=4)=[N:20][C:6]2=3)[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 433732804-amino-N-(1-methylpiperidin-4-yl)benzamideHCID 579556112-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

Product 1

HCID 580151484-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamideYield 35.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 0.05 g (0.17 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-20), 0.05 g (0.20 mmole) of 4-amino-N-(1-methyl-piperidin-4-yl)-benzamide and 0.05 g (0.25 mmole) of p-toluenesulfonic acid monohydrate in 4.0 mL of 2-propanol was heated at 160 degrees for 2 hours in a microwave reactor. The reaction mixture was cooled and then concentrated under reduced pressure. The residue was diluted with dichloromethane and saturated aqueous sodium bicarbonate solution. The precipitate was collected by filtration, washed with water and dried to give 0.030 g of 4-(9-cyclopentyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide (I-134).

Workup

  1. temperaturewas heated at 160 degrees for 2 hours in a microwave reactor
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with dichloromethane and saturated aqueous sodium bicarbonate solution
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-13f903d1188a4528b3e09282ea1a1918
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Linked notes

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