4-Amino-2-fluoro-5-methoxybenzoic acid → 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 1880993Notes

Reaction equation

HRID 1880993 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:21])[C:7](=[O:20])[C:8]([F:19])([F:18])[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[NH2:22][C:23]1[C:31]([O:32][CH3:33])=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[C:25]([F:34])[CH:24]=1>Cl.CC(O)C>[CH:13]1([N:10]2[CH2:9][C:8]([F:19])([F:18])[C:7](=[O:20])[N:6]([CH3:21])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[C:31]([O:32][CH3:33])=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[C:25]([F:34])[CH:24]=4)=[N:12][C:11]2=3)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 2

HCID 529829634-Amino-2-fluoro-5-methoxybenzoic acidHCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

Product 1

HCID 252536794-(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

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Procedure

2-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (158 mg, 0.5 mmol), 4-amino-2-fluoro-5-methoxy benzoic acid (obtained above), i-PrOH (5 mL) and conc. HCl (10 drops) were heated to 100° C. overnight. The reaction mixture was then cooled to room temperature. The reaction mixture contains desired product plus lots of de-carboxylation byproduct, which were separated by RP-HPLC to give the product as a white solid (12 mg). [M+H] calc'd for C21H22F3N5O4, 466; found 466.

Sources & evidence

ORD record
ord-cd12a6b5bfb44599b91e27bdc01bbd69
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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