Trifluoroacetic acid → HCID 131736426, compound

HRID 1056407Notes

Reaction equation

HRID 1056407 reaction equation
[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[C:6]([C:13]3[NH:17][C:16]4[C@@H:18]([CH3:22])[NH:19][C:20](=[O:21])[C:15]=4[CH:14]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1[NH:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30]C(=O)OC(C)(C)C)[CH2:25]1.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39]>C(Cl)Cl>[OH:44][C:38]([C:40]([F:43])([F:42])[F:41])=[O:39].[NH2:30][C@@H:26]1[CH2:27][CH2:28][CH2:29][C@H:24]([NH:23][C:3]2[N:2]([CH3:1])[C:11](=[O:12])[C:10]3[C:5](=[C:6]([C:13]4[NH:17][C:16]5[C@@H:18]([CH3:22])[NH:19][C:20](=[O:21])[C:15]=5[CH:14]=4)[CH:7]=[CH:8][CH:9]=3)[N:4]=2)[CH2:25]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 129012624HCID 129012624, compound

Product 1

HCID 131736426HCID 131736426, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (rac)-tert-butyl ((cis)-3-((3-methyl-8-((R)-6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-4-oxo-3,4-dihydroquinazolin-2-yl)amino)cyclohexyl)carbamate (509, see below) (47 mg, 0.093 mmol) and TFA (71.5 pt, 0.928 mmol) in DCM (928 pt) was stirred at RT for 1.5 h when mostly product was observed via LCMS. The reaction mixture was concentrated to give (rac)-2-(((cis)-3-aminocyclohexyl)amino)-3-methyl-8-((R)-6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one TFA salt (506, 48 mg, 0.092 mmol, 99% yield) as an off-white solid and a 2.6:1 ratio of diastereomers via LCMS and 1.3:1 via 1H NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21-1.33 (m, 1H) 1.33-1.46 (m, 5H) 1.46-1.56 (m, 1H) 1.89 (d, J=12.72 Hz, 1H) 1.98 (d, J=11.74 Hz, 1H) 2.06 (d, J=10.56 Hz, 1H) 2.30-2.39 (m, 1H) 3.05-3.17 (m, 1H) 3.45 (s, 3H) 4.01-4.15 (m, 1H) 4.50-4.61 (m, 1H) 6.93-7.01 (m, 1H) 7.06 (d, J=4.11 Hz, 1H) 7.17 (t, J=7.63 Hz, 1H) 7.62 (s, 0.42H) 7.66 (s, 0.58; H) 7.84 (d, J=7.63 Hz, 1H) 7.88-8.00 (m, 3H) 11.78 (s, 0.42; H) 11.91 (s, 0.58; H). 19F NMR (376 MHz, DMSO-d6) δ ppm −73.81 (s, 3F). MS (ESI, pos. ion) m/z: 407.1 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-70d64a6fed7f43828431a7ea714c32a7
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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