Hydrochloric Acid → HCID 178450282, compound

HRID 2271813Notes

Reaction equation

HRID 2271813 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]([O:37][CH3:38])[C:34]([OH:39])=[C:33]([Cl:40])[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]([O:37][CH3:38])[C:34]([OH:39])=[C:33]([Cl:40])[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 178450283HCID 178450283, compound

Product 1

HCID 178450282HCID 178450282, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of tert-butyl (trans-4-((3-butyryl-6-(3-chloro-4-hydroxy-5-methoxyphenyl)quinolin-4-yl)amino)cyclohexyl)carbamate (36 mg, 0.063 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 (22 mg, 75%) as a yellow solid. 1H NMR (500 MHz, MeOD) δ 8.96 (s, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.02 (dd, J=8.7, 2.0 Hz, 1H), 7.90 (d, J=8.7 Hz, 1H), 7.28 (d, J=2.1 Hz, 1H), 7.20 (d, J=2.1 Hz, 2H), 4.24-4.18 (m, 1H), 3.98 (s, 3H), 3.11-3.00 (m, 3H), 2.37 (d, J=12.9 Hz, 2H), 2.10 (d, J=12.2 Hz, 2H), 1.84-1.74 (m, J=7.4 Hz, 2H), 1.71-1.65 (m, J=12.6 Hz, 2H), 1.49-1.43 (m, 2H), 1.04 (t, J=7.4 Hz, 3H). ESI MS m/z 468 [C26H30ClN3O3+H]+; HPLC>99% (AUC), tR=10.17 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-dc0ea64d7ee64e2ca48f25f06ff827c3
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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