Hydrochloric Acid → HCID 178467111, compound

HRID 2271807Notes

Reaction equation

HRID 2271807 reaction equation
[C:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([NH:21]C(=O)OC(C)(C)C)[CH2:17][CH2:16]1)=[CH:11][C:10]([C:29]1[CH:34]=[C:33]([F:35])[C:32]([OH:36])=[C:31]([Cl:37])[CH:30]=1)=[CH:9][CH:8]=2)(=[O:3])[CH3:2].O.Cl>C1COCC1>[NH2:21][C@H:18]1[CH2:19][CH2:20][C@H:15]([NH:14][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([C:29]4[CH:34]=[C:33]([F:35])[C:32]([OH:36])=[C:31]([Cl:37])[CH:30]=4)[CH:11]=3)[N:6]=[CH:5][C:4]=2[C:1](=[O:3])[CH3:2])[CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 178467113HCID 178467113, compound

Product 1

HCID 178467111HCID 178467111, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of tert-butyl (trans-4-((3-acetyl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-4-yl)amino)cyclohexyl)carbamate (38 mg, 0.072 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 purified by preparative HPLC (C18 silica, 10-90% methanol/water with 0.05% TFA). The residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia) to obtain the desired product (18.1 mg, 59%) as a yellow solid. 1H NMR (500 MHz, MeOD+TFA-d) δ 9.12 (s, 1H), 8.47 (s, 1H), 8.32-8.26 (m, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.59 (s, 1H), 7.52 (d, J=11.5 Hz, 1H), 4.57-4.53 (m, 1H), 2.74 (s, 3H), 2.51 (d, J=12.3 Hz, 2H), 2.26 (d, J=12.3 Hz, 2H), 1.87 (q, J=12.5 Hz, 2H), 1.71-1.62 (m, 2H). ESI MS m/z 428 [C23H23ClFN3O2+H]+; HPLC>99% (AUC), tR=9.43 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. customThe resultant residue was purified by preparative HPLC (C18 silica, 10-90% methanol/water with 0.05% TFA)
  4. washThe residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia)

Sources & evidence

ORD record
ord-b31d1e745e5a4a28b9d68107c9329573
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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