2486-69-3 → 4-[7,7-difluoro-5-methyl-6-oxo-9-(trans-2-phenyl-cyclopropyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-benzoic acid

HRID 1676821Notes

Reaction equation

HRID 1676821 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:18][CH:17]3[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:6]=2[N:25]=1.[NH2:26][C:27]1[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][C:28]=1[O:36][CH3:37]>C(O)C.O.Cl>[F:14][C:9]1([F:15])[CH2:8][N:7]([C@@H:16]2[CH2:18][C@H:17]2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:6]2[N:25]=[C:2]([NH:26][C:27]3[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][C:28]=3[O:36][CH3:37])[N:3]=[CH:4][C:5]=2[N:11]([CH3:12])[C:10]1=[O:13]

Participants

4

Reactant 2

HCID 2880572486-69-3HCID 866375202-Chloro-7,7-difluoro-5-methyl-9-(2-phenyl-cyclopropyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Product 1

HCID 670759434-[7,7-difluoro-5-methyl-6-oxo-9-(trans-2-phenyl-cyclopropyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-benzoic acidYield 69.9%

Reagents, catalysts & solvents 1

HCID 86604601Ethanol water hydrochloric acidSolvent

Procedure

A mixture of 1.0 g (0.0028 mole) of 2-chloro-7,7-difluoro-5-methyl-9-(2-phenyl-cyclopropyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-287) and 0.55 g (0.0034 mole) of 4-amino-3-methoxy-benzoic acid in 6.4 mL of ethanol-water-hydrochloric acid (20:80:1) was refluxed for 18 hours, then cooled and partially concentrated under reduced pressure. The resulting solid was collected by filtration, washed with water and dried to give 0.97 g of 4-[7,7-difluoro-5-methyl-6-oxo-9-(trans-2-phenyl-cyclopropyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-benzoic acid (I-287).

Workup

  1. temperaturewas refluxed for 18 hours
  2. temperaturecooled
  3. concentrationpartially concentrated under reduced pressure
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with water
  6. customdried

Sources & evidence

ORD record
ord-5a8ef3863542456ea6e43767ca5c9ec0
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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