Hydrochloric Acid → 2-Chloro-9-cyclopentyl-7-ethyl-7-fluoro-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

HRID 1880937Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH2:14][C:15]([F:23])([CH2:21][CH3:22])[C:16](OCC)=[O:17])[CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:5]([N+:24]([O-])=O)=[CH:4][N:3]=1.Cl>C(O)(=O)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:24][C:16](=[O:17])[C:15]([CH2:21][CH3:22])([F:23])[CH2:14][N:8]([CH:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of ethyl 2-(((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)methyl)-2-fluorobutanoate (2.6 g, 6 mmol), reduced iron (840 mg, 15 mmol) in acetic acid (20 ml) was added dropwise concentrated hydrochloric acid (2 ml) at 0° C. The reaction mixture was stirred at 60° C. for 18 h. It was then concentrated in vacuo, diluted to EtOAc, basified with 10% NaOH solution at 0° C. The whole was filtered through celite, washed with EtOAc. The filtrate was then separated. The organic layer was dried over Na2SO4. The solution was concentrated in vacuo followed by precipitation from ether to afford the product (0.9 g, 48% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (t, J=7.3 Hz, 3 H) 1.53-1.91 (m, 10 H) 3.53-3.69 (m, 1 H) 3.78 (d, J=13.4 Hz, 1 H) 5.05 (t, J=8.5 Hz, 1 H) 7.96 (s, 1 H) 10.31 (d, J=1.5 Hz, 1 H). [M+H] calc'd for C14H18ClFN4O, 313; found 313.

Workup

concentrationIt was then concentrated in vacuo
additiondiluted to EtOAc
custombasified with 10% NaOH solution at 0° C
filtrationThe whole was filtered through celite
washwashed with EtOAc
customThe filtrate was then separated
dry with materialThe organic layer was dried over Na2SO4
concentrationThe solution was concentrated in vacuo
customfollowed by precipitation from ether

Sources & evidence

ORD record: ord-c6fd50b16e6c4150987239b475ac60ce
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318727B2

Reaction notes

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