Trifluoroacetic acid → Trifluoroacetic acid

HRID 1398466Notes

Reaction equation

HRID 1398466 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[N:11][CH:10]=[C:9]2[C:4]=1[C:5]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C@@H:21]([NH:26]C(=O)OC(C)(C)C)[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:15][C:6]=1[N:7]([CH3:14])[C:8]2=[O:13].[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35]>C(Cl)Cl>[NH2:26][C@@H:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:16]1[CH:17]=[CH:18][C:5]2[C:4]3[C:9](=[CH:10][N:11]=[CH:12][C:3]=3[O:2][CH3:1])[C:8](=[O:13])[N:7]([CH3:14])[C:6]=2[CH:15]=1.[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86710440HCID 86710440, compound

Product 2

HCID 6422Trifluoroacetic acidYield 69%HCID 73214525HCID 73214525, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution of (S)-tert-butyl (1-((1-methoxy-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (40 mg, 0.041 mmol) in DCM (0.9 mL) cooled to 0° C., TFA (0.2 mL, 2.60 mmol) was added dropwise and stirred for 5 min. The reaction mixture was warmed to rt and stirred for 3 h. The volatiles were removed under reduced pressure. The crude product was purified by prep HPLC using (0.1% TFA in ACN:water) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-1-methoxy-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one, 2 TFA (17.11 mg, 0.028 mmol, 69% yield) as white solid. LC/MS (ESI) m/e 356.0 [(M+H)+, calcd for C20H26N3O3 356.2]; LC/MS retention time (method C): tR=1.82 min; HPLC retention time (method A): tR=9.44 min; HPLC retention time (method B): tR=9.78 min; 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.17 (s, 1H), 9.14 (d, J=9.0 Hz, 1H), 8.54 (s, 1H), 7.09 (d, J=2.5 Hz, 1H), 7.02 (dd, J=9.0, 2.5 Hz, 1H), 4.21 (s, 3H), 4.19-4.15 (m, 1H), 4.04-3.95 (m, 2H), 3.78 (s, 3H), 1.97-1.80 (m, 1H), 1.51-1.42 (m, 2H), 1.04 (d, J=6.5 Hz, 3H), 1.02 (d, J=6.5 Hz, 3H).

Workup

  1. stirringstirred for 3 h
  2. customThe volatiles were removed under reduced pressure
  3. customThe crude product was purified by prep HPLC

Sources & evidence

ORD record
ord-fe86b358f36e40e09e9a855c704505fa
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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