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

HRID 1880860Notes

Reaction equation

HRID 1880860 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]([F:20])([F:19])[CH2:9][N:10]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][C:25]=1[O:33][CH3:34]>Cl.CC(O)C>[CH:13]1([N:10]2[CH2:9][C:8]([F:20])([F:19])[C:7](=[O:21])[N:6]([CH3:22])[C:5]3[CH:4]=[N:3][C:2]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])=[N:12][C:11]2=3)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 2

HCID 2880572486-69-3HCID 579555542-Chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Product 1

HCID 252536804-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acidYield 70%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Procedure

2-Chloro-9-cyclohexyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (2.77 g, 8.8 mmol), 4-amino-3-methoxy benzoic acid (1.61 g, 9.6 mmol), i-PrOH (30 mL) and conc. HCl (30 drops) were heated to 95° C. for 18 hours. A this time the reaction was cooled to room temperature and filtered to reveal the product as a tan solid (2.74 g, 70% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (d, J=12.13 Hz, 1 H) 1.23-1.42 (m, 2 H) 1.53-1.78 (m, 5 H) 1.82 (d, J=12.63 Hz, 2 H) 3.32 (s, 3 H) 3.94 (s, 3 H) 4.26 (t, J=12.38 Hz, 2 H) 4.52 (t, J=11.62 Hz, 1 H) 7.47-7.65 (m, 2 H) 8.13 (d, J=8.08 Hz, 1 H) 8.28-8.45 (m, 1 H) 9.43 (br. s., 1 H). [M+H] calc'd for C22H25F2N5O4, 462; found 462.

Workup

  1. filtrationfiltered

Sources & evidence

ORD record
ord-26b6a27e74e2469fb460d46c111a8b42
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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