Ethanol → 4-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide

HRID 2111416Notes

Reaction equation

HRID 2111416 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([CH3:15])([CH3:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[CH3:22][N:23]1[CH2:28][CH2:27][CH:26]([NH:29][S:30]([C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-])=O)=[CH:35][CH:34]=2)(=[O:32])=[O:31])[CH2:25][CH2:24]1.C(O)C.O>Cl.C(OCC)(=O)C>[CH:16]1([N:7]2[CH2:8][C:9]([CH3:15])([CH3:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:39][C:36]4[CH:35]=[CH:34][C:33]([S:30]([NH:29][CH:26]5[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]5)(=[O:32])=[O:31])=[CH:38][CH:37]=4)=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 702EthanolHCID 962WaterHCID 22772515N-(1-methyl-piperidin-4-yl)-4-nitro-benzenesulfonamideHCID 592951162-Chloro-9-cyclopentyl-5,7,7-trimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Product 1

HCID 576350104-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzenesulfonamideYield 42.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.0203 g (0.000066 mole) of 2-chloro-9-cyclopentyl-5,7,7-trimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-38), 0.0207 g (0.000077 mole) of N-(1-methyl-piperidin-4-yl)-4-nitro-benzenesulfonamide, 0.6 mL of ethanol, 2.4 mL of water and 2 drops of hydrochloric acid was heated at reflux for 17 hrs. The mixture was taken up in 50 mL of ethyl acetate and washed successively twice with 7 mL of 1M sodium hydroxide, twice with 7 mL of water and 7 mL of brine. The organic layer was concentrated under reduced pressure and the residue purified by silica gel chromatography, elution with dichloromethane-methanol 95:5-80:20) gave 0.0151 g of 4-(9-cyclopentyl-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzenesulfonamide (I-64) as an off-white solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 17 hrs
  3. washwashed successively twice with 7 mL of 1M sodium hydroxide, twice with 7 mL of water and 7 mL of brine
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customthe residue purified by silica gel chromatography, elution with dichloromethane-methanol 95:5-80:20)

Sources & evidence

ORD record
ord-ba9965d88b50430e954503a6834ba400
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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