8-Bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one → 8-Bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one

HRID 1056335Notes

Reaction equation

HRID 1056335 reaction equation
Br[C:2]1[C:3](F)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=C(NC(C)(C)C)[N:8](C)[C:7]2=[O:18].BrC1C(F)=CC=C2C=1N=C(Cl)N(C1CC1)C2=O.[Br:37][C:38]1[C:39]([F:57])=[CH:40][CH:41]=[C:42]2[C:47]=1[N:46]=[C:45]([NH:48][C:49]([CH3:52])([CH3:51])[CH3:50])[N:44]([CH:53]1[CH2:55][CH2:54]1)[C:43]2=[O:56]>>[Br:37][C:38]1[C:39]([F:57])=[CH:40][CH:41]=[C:42]2[C:47]=1[N:46]=[C:45]([NH:48][C:49]([CH3:50])([CH3:51])[CH3:52])[N:44]([CH:53]1[CH2:54][CH2:55]1)[C:43]2=[O:56].[C:49]([NH:48][C:45]1[N:44]([CH:53]2[CH2:55][CH2:54]2)[C:43](=[O:56])[C:42]2[C:47](=[C:38]([C:4]3[NH:10][C:11]4[C@@H:2]([CH3:3])[NH:8][C:7](=[O:18])[C:6]=4[CH:5]=3)[C:39]([F:57])=[CH:40][CH:41]=2)[N:46]=1)([CH3:52])([CH3:51])[CH3:50]

Participants

5

Reactant 3

HCID 897819198-Bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-oneHCID 897819758-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-oneHCID 897822708-bromo-2-(tert-butylamino)-7-fluoro-3-methylquinazolin-4(3H)-one

Product 2

HCID 897819198-Bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-oneYield 85%HCID 89783781(R)-2-(tert-butylamino)-3-cyclopropyl-7-fluoro-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-oneYield 51%

Procedure

8-Bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (461a, 288 mg, 85%) as a brown foam was prepared according to the procedures described for Intermediate 405a, starting from 8-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (721) (305 mg, 0.96 mmol). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.90 (1H, dd, J=8.7, 6.4 Hz), 7.04 (1H, t, J=8.7 Hz), 6.25 (1H, s), 2.76-2.88 (1H, m), 1.57 (9H, s), 1.18-1.27 (2H, m), 0.69-0.81 (2H, m). m/z (ESI, +ve ion) 354.0/356.0 (M+H)+. (R)-2-(tert-butylamino)-3-cyclopropyl-7-fluoro-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (461) (171 mg, 51%) as a white solid was prepared according to the procedures described for Example 407, starting from 8-bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (461a, 288 mg, 0.81 mmol). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.79 (1H, s), 7.90 (1H, dd, J=8.8, 6.5 Hz), 7.59 (1H, s), 7.04 (1H, dd, J=10.1, 8.9 Hz), 6.35 (1H, t, J=1.8 Hz), 6.15 (1H, s), 4.49 (1H, q, J=6.5 Hz), 2.76-2.88 (1H, m), 1.40 (9H, s), 1.34 (3H, d, J=6.5 Hz), 1.19-1.28 (2H, m), 0.70-0.78 (2H, m). 19F NMR (377 MHz, DMSO-d6) δ ppm −105.25 (s). m/z (ESI, +ve ion) 410.1 (M+H)+.

Sources & evidence

ORD record
ord-2fa75385f3f8441196257cf8e26e7d65
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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