Hydrochloric Acid → HCID 178450288, compound

HRID 2271811Notes

Reaction equation

HRID 2271811 reaction equation
[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([NH:23]C(=O)OC(C)(C)C)[CH2:19][CH2:18]1)=[CH:13][C:12]([C:31]1[CH:36]=[C:35]([F:37])[C:34]([OH:38])=[C:33]([Cl:39])[CH:32]=1)=[CH:11][CH:10]=2)(=[O:5])[CH2:2][CH2:3][CH3:4].O.Cl>C1COCC1>[NH2:23][C@H:20]1[CH2:21][CH2:22][C@H:17]([NH:16][C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:31]4[CH:36]=[C:35]([F:37])[C:34]([OH:38])=[C:33]([Cl:39])[CH:32]=4)[CH:13]=3)[N:8]=[CH:7][C:6]=2[C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 178450290HCID 178450290, compound

Product 1

HCID 178450288HCID 178450288, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of tert-butyl (trans-4-((3-butyryl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-4-yl)amino)cyclohexyl)carbamate (36 mg, 0.065 mmol) in THF (3 mL) was added water (2 mL) and 6N aqueous HCl (2 mL). The resultant solution was heated at 65° C. for 4 h. The reaction mixture was cooled and concentrated. The resultant residue was triturated with diethyl ether. The residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia) to obtain the desired product (21.1 mg, 71%) as a yellow solid. 1H NMR (500 MHz, MeOD+TFA-d) δ 9.15 (s, 1H), 8.47 (s, 1H), 8.28 (dd, J=8.7, 1.8 Hz, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.59 (s, 1H), 7.51 (d, J=11.4 Hz, 1H), 4.55 (br s, 1H), 3.13 (t, J=7.2 Hz, 2H), 2.53-2.49 (m, 2H), 2.26 (d, J=12.1 Hz, 2H), 1.94-1.74 (m, 4H), 1.68-1.62 (m, 2H), 1.06 (t, J=7.4 Hz, 3H). ESI MS m/z 456 [C25H27ClFN3O2+H]+; HPLC>99% (AUC), tR=10.83 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. customThe resultant residue was triturated with diethyl ether
  4. washThe residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia)

Sources & evidence

ORD record
ord-0af027a56fe840a993fee4ac64f7a56f
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

Loading…