Hydrochloric Acid → HCID 178467107, compound

HRID 2271832Notes

Reaction equation

HRID 2271832 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]([CH2:21][N:22]3[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)[CH2:17][CH2:16]1)=[CH:11][C:10]([C:35]1[CH:40]=[C:39]([F:41])[C:38]([OH:42])=[C:37]([Cl:43])[CH:36]=1)=[CH:9][CH:8]=2)(=[O:3])[CH3:2].O.[ClH:45]>C1COCC1>[ClH:43].[ClH:45].[Cl:43][C:37]1[CH:36]=[C:35]([C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][CH:9]=2)[N:6]=[CH:5][C:4]([C:1](=[O:3])[CH3:2])=[C:13]3[NH:14][C@H:15]2[CH2:20][CH2:19][C@H:18]([CH2:21][N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH2:17][CH2:16]2)[CH:40]=[C:39]([F:41])[C:38]=1[OH:42]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 178467108HCID 178467108, compound

Product 1

HCID 178467107HCID 178467107, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of tert-butyl 4-((trans-4-((3-acetyl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-4-yl)amino)cyclohexyl)methyl)piperazine-1-carboxylate (66 mg, 0.10 mmol) in THF (5 mL) was added water (5 mL) and aqueous 6 N HCl (1.0 mL). The reaction mixture was heated at 65° C. for 2 h, cooled to room temperature and concentrated. The resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TFA). The residue was dissolved in methanol (5 mL) and HCl (6 M in water, 0.5 mL, 3 mmol) was added. The resultant solution was concentrated to give the desired product (24.2 mg, 41%) as an off-white solid. 1H NMR (500 MHz, MeOD) δ 9.10 (s, 1H), 8.48 (s, 1H), 8.27 (dd, J=8.7, 1.7 Hz, 1H), 7.98 (d, J=8.7 Hz, 1H), 7.59 (s, 1H), 7.52 (d, J=11.3 Hz, 1H), 4.57-4.53 (br s, 1H), 3.67 (br s, 4H), 3.50 (br s, 2H), 3.17 (br s, 2H), 2.74 (s, 3H), 2.46 (d, J=11.9 Hz, 2H), 2.18 (d, J=12.5 Hz, 2H), 2.10 (br s, 1H), 1.83-1.77 (m, 2H), 1.41-1.34 (m, 2H). ESI MS m/z 511 [C28H32ClFN4O2+H]+; HPLC 98.3% (AUC), tR=9.38 min.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customThe resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TFA)
  4. dissolutionThe residue was dissolved in methanol (5 mL)
  5. concentrationThe resultant solution was concentrated

Sources & evidence

ORD record
ord-d176f4c5309d4c07b4769300a998eed0
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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