Hydrochloric Acid → HCID 71726769, compound

HRID 870952Notes

Reaction equation

HRID 870952 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH2:9][C@@H:10]([NH:15]C(=O)OC(C)(C)C)[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:6][C:5]2[O:23][CH:24]([C:31]([F:34])([F:33])[F:32])[C:25]3[C:30]([C:4]=2[CH:3]=1)=[CH:29][CH:28]=[N:27][CH:26]=3.Cl.C(OCC)C>C(Cl)Cl>[Cl:1][C:2]1[C:7]([O:8][CH2:9][C@@H:10]([NH2:15])[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:6][C:5]2[O:23][CH:24]([C:31]([F:33])([F:34])[F:32])[C:25]3[C:30]([C:4]=2[CH:3]=1)=[CH:29][CH:28]=[N:27][CH:26]=3

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86724441HCID 86724441, compound

Product 1

HCID 71726769HCID 71726769, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl ((2S)-1-((9-chloro-5-(trifluoromethyl)-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (50 mg, 0.100 mmol) in DCM (10 mL) was added 1M HCl in diethyl ether (0.100 mmol) at room temperature and the solution stirred for 14 h. The solvent was removed under reduced pressure to afford a residue which was purified by preparative HPLC using 0.1% TFA in methanol. The purification afforded (2S)-1-((9-chloro-5-(trifluoromethyl)-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-amine (10 mg, 0.023 mmol, 23% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J=5.2 Hz, 1H), 8.57 (s, 1H), 8.32 (s, 1H), 7.98 (d, J=5.2 Hz, 1H), 6.97 (s, 1H), 6.45 (m, 1H), 3.9 (m, 1H), 3.87 (m, 1H), 3.09 (m, 1H), 1.83 (m, 1H), 1.33 (m, 2H), 1.31-1.26 (m, 6H); LCMS (ESI) m/e 401.2 [(M+H), calcd for C19H21ClF3N2O2 401.1]; LC/MS retention time (Method C): tR=1.69 min; HPLC retention time (method A): tR=5.80 min, 5.87 min (diastereomeric mixture); HPLC retention time (method B): tR=6.41 min, 6.45 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-2ff777e2a5c4490489f5b638a3b7c2ac
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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