8-Bromo-3-cyclopropyl-7-fluoro-2-((1-methylcyclobutyl)amino)quinazolin-4(3H)-one → (R)-3-Cyclopropyl-7-fluoro-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-one

HRID 1056384Notes

Reaction equation

HRID 1056384 reaction equation
Br[C:2]1[C:3]([F:22])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]1(C)[CH2:16][CH2:15][CH2:14]1)[N:8]([CH:18]1[CH2:20][CH2:19]1)[C:7]2=[O:21].[CH3:23][C@@H:24]1[C:28]2[NH:29][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:31][C:27]=2[C:26](=[O:41])[NH:25]1>>[CH:18]1([N:8]2[C:7](=[O:21])[C:6]3[C:11](=[C:2]([C:30]4[NH:29][C:28]5[C@@H:24]([CH3:23])[NH:25][C:26](=[O:41])[C:27]=5[CH:31]=4)[C:3]([F:22])=[CH:4][CH:5]=3)[N:10]=[C:9]2[NH:12][C:13]2([CH3:16])[CH2:14][CH2:15]2)[CH2:19][CH2:20]1

Participants

3

Reactant 2

HCID 897819228-Bromo-3-cyclopropyl-7-fluoro-2-((1-methylcyclobutyl)amino)quinazolin-4(3H)-oneHCID 89781988(R)-6-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one

Product 1

HCID 89783486(R)-3-Cyclopropyl-7-fluoro-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-oneYield 51.7%

Procedure

(R)-3-Cyclopropyl-7-fluoro-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-one (78 mg, 50% yield) as a light yellow solid was prepared according to the procedure described for Example 495, using 8-bromo-3-cyclopropyl-7-fluoro-2-((1-methylcyclobutyl)amino)quinazolin-4(3H)-one (498a; 137 mg, 0.37 mmol) and boronic ester 705 (147 mg, 0.45 mmol) as starting material. MS (ESI, pos. ion) m/z: 422 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 12.23 (1H, s), 7.86 (1H, dd, J=8.8, 6.3 Hz), 7.66 (1H, s), 6.98-7.14 (2H, m), 6.51 (1H, d, J=1.8 Hz), 4.57 (1H, q, J=6.6 Hz), 2.72-2.84 (1H, m), 2.35-2.44 (2H, m), 2.06 (2H, dt, J=12.3, 6.1 Hz), 1.78-1.91 (2H, m), 1.59 (3H, s), 1.39 (3H, d, J=6.7 Hz), 1.16-1.31 (2H, m), 0.75-0.83 (2H, m).

Sources & evidence

ORD record
ord-12d4c7758dc743dab579ba0bd90cf001
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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