Sodium Hydroxide → 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxybenzoic acid

HRID 1676702Notes

Reaction equation

[OH-].[Na+].C[O:4][C:5](=[O:36])[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([NH:14][C:15]2[N:16]=[CH:17][C:18]3[N:24]([CH3:25])[C:23](=[O:26])[C:22]([F:28])([F:27])[CH2:21][N:20]([CH:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[C:19]=3[N:34]=2)=[CH:8][C:7]=1[F:35]>O1CCCC1CO>[CH:29]1([N:20]2[CH2:21][C:22]([F:28])([F:27])[C:23](=[O:26])[N:24]([CH3:25])[C:18]3[CH:17]=[N:16][C:15]([NH:14][C:9]4[C:10]([O:12][CH3:13])=[CH:11][C:6]([C:5]([OH:36])=[O:4])=[C:7]([F:35])[CH:8]=4)=[N:34][C:19]2=3)[CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

Conditions

Temperature: 50 °C

Procedure

An aqueous solution of 5 mL of aqueous 2M (0.010 mole) of sodium hydroxide was added to a solution of 0.51 g (0.00106 mole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl amino)-2-fluoro-5-methoxy-benzoic acid methyl ester (I-168) in 20 mL of tetrahydrofuran-methanol (3:1). The mixture was heated at 50° C. for 18 hours and then concentrated under reduced pressure. The residue was dissolved in water and acidified to pH 2 with 2M hydrochloric acid. After stirring for 30 minutes, the solid was collected by filtration, washed with water and dried to give 0.50 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxy-benzoic acid (I-169).

Workup

concentrationconcentrated under reduced pressure
dissolutionThe residue was dissolved in water
filtrationthe solid was collected by filtration
washwashed with water
customdried

Sources & evidence

ORD record: ord-d26453e9109048ac9f5dea4c29c5798d
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003785B2

Reaction notes

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