Trifluoroacetic acid → HCID 71726887, compound

HRID 2369544Notes

Reaction equation

HRID 2369544 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:9][O:10][C:11]1[C:12]([Br:29])=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:18]([C:25]([F:28])([F:27])[F:26])[O:17][C:15]=2[CH:16]=1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[Br:29][C:12]1[C:11]([O:10][CH2:9][C@@H:8]([NH2:7])[CH2:30][CH:31]([CH3:33])[CH3:32])=[CH:16][C:15]2[O:17][CH:18]([C:25]([F:27])([F:28])[F:26])[C:19]3[C:24]([C:14]=2[CH:13]=1)=[CH:23][CH:22]=[N:21][CH:20]=3

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86724442HCID 86724442, compound

Product 1

HCID 71726887HCID 71726887, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl((2S)-1-((9-bromo-5-(trifluoromethyl)-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (50 mg, 0.092 mmol) in dichloromethane (10 mL) at room temperature was added TFA (0.035 mL, 0.458 mmol) and stirred overnight. The solvent was removed under reduced pressure to afford a residue which was purified by preparative HPLC using 0.1% TFA in MeOH. The purification afforded (2S)-1-((9-bromo-5-(trifluoromethyl)-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-amine (15 mg, 0.033 mmol, 36% yield) as a yellow solid. 1H NMR (400 MHz, MeOD) δ 8.64 (m, 1 H), 8.54 (m, 1 H), 8.23 (m, 1 H), 7.88 (s, 1 H), 6.91 (s, 1 H), 6.10 (m, 1 H), 4.3 (m, 1 H), 4.12 (m, 1 H), 3.52 (m, 1 H), 1.85 (m, 1 H), 1.72-1.69 (m, 1 H), 1.61-1.56 (m, 1 H), 1.05 (m, 6 H). LCMS (ESI) m/e 445.2 [(M+H)+, calcd for C19H21BrF3N2O2 445.1]; LC/MS retention time (Method C): tR=1.74 min; HPLC retention time (method A): tR=5.66 min, 5.75 min (diastereomeric mixture); HPLC retention time (method B): tR=6.27 min, 6.34 min (diastereomeric mixture).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto afford a residue which
  3. customwas purified by preparative HPLC
  4. customThe purification

Sources & evidence

ORD record
ord-f3961bdfbce540ed94e54e1fb564761c
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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