Trifluoroacetic acid → HCID 86727513, compound

HRID 519128Notes

Reaction equation

HRID 519128 reaction equation
C(OC([N:8]1[CH2:11][C:10]([CH3:34])([C@H:12]([C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][C:27]=2[C:28]([F:31])([F:30])[F:29])[O:24][CH2:23][C:22]2[N:17]3[C@H:18]([CH3:33])[C:19](=[O:32])[NH:20][N:21]=2)[CH3:13])[CH2:9]1)=O)(C)(C)C.[C:35]([OH:41])([C:37]([F:40])([F:39])[F:38])=[O:36]>C(Cl)Cl>[F:38][C:37]([F:40])([F:39])[C:35]([OH:41])=[O:36].[CH3:33][C@H:18]1[N:17]2[C:22]([CH2:23][O:24][C:25]3[C:16]2=[CH:15][C:14]([C@H:12]([C:10]2([CH3:34])[CH2:9][NH:8][CH2:11]2)[CH3:13])=[C:27]([C:28]([F:29])([F:31])[F:30])[CH:26]=3)=[N:21][NH:20][C:19]1=[O:32]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86727516HCID 86727516, compound

Product 1

HCID 86727513HCID 86727513, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-methyl-3-[(S)-1-((R)-4-methyl-3-oxo-7-trifluoromethyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-azetidine-1-carboxylic acid tert-butyl ester (diastereomer 2, 0.009 g, 0.019 mmol) in DCM (2 mL) was added TFA (0.5 mL) and the reaction mixture was stirred at ambient temperature for 1.5 h. The solvent was removed in vacuo and the residue was purified by prep-HPLC (Table 3, Method 28) to give (R)-4-methyl-6-[(S)-1-(3-methyl-azetidin-3-yl)-ethyl]-7-trifluoromethyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one trifluoroacetic acid (Example #147-2, Enantiomer 2, 0.006 g, 84%) as a solid. 1H NMR (CD3OD-d4, 400 MHz): δ 7.35 (s, 1H), 6.9 (s, 1H), 4.95 (m, 1H), 4.7 (d, J=12.0 Hz, 2H), 4.4 (d, J=11.2 Hz, 1H), 4.2 (d, J=11.2 Hz, 1H), 3.65 (t, J=8.4 Hz, 2H), 3.26 (m, 1H), 1.5 (m, 6H), 1.45 (m, 3H). LC/MS (Table 1, Method 5) Rt=2.310 min; MS m/z: 383 [M+H]+. SFC (Table 1, Method 36) Rt=4.712 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by prep-HPLC (Table 3, Method 28)

Sources & evidence

ORD record
ord-b7857c61adc94705b08205c1391bd6fa
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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