Hydrochloric Acid → 8-hydroxy-5-[(1R)-1-hydroxy-2-[2-[4-(4-methoxy-3-phenylanilino)phenyl]ethylamino]ethyl]-1H-quinolin-2-one

HRID 730924Notes

Reaction equation

HRID 730924 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][NH:24][CH2:25][C@H:26]([OH:46])[C:27]4[CH:36]=[CH:35][C:34]([O:37]CC5C=CC=CC=5)=[C:33]5[C:28]=4[CH:29]=[CH:30][C:31](=[O:45])[NH:32]5)=[CH:18][CH:17]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H].Cl>O1CCCC1.O.[Pd].C(#N)C>[C:1]1([C:7]2[CH:8]=[C:9]([NH:15][C:16]3[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][NH:24][CH2:25][C@H:26]([OH:46])[C:27]4[CH:36]=[CH:35][C:34]([OH:37])=[C:33]5[C:28]=4[CH:29]=[CH:30][C:31](=[O:45])[NH:32]5)=[CH:20][CH:21]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 3

HCID 313Hydrochloric Acid2×HCID 20605084HCID 20605084, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 98713868-hydroxy-5-[(1R)-1-hydroxy-2-[2-[4-(4-methoxy-3-phenylanilino)phenyl]ethylamino]ethyl]-1H-quinolin-2-one

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{2-[4-(3-phenyl-4-methoxyphenyl)aminophenyl]ethyl}-(R)-2-hydroxy-2-(8-benzyloxy-2(1H)-quinolinon-5-yl)ethylamine (PP) (4.0 g, 6.5 mmol) in tetrahydrofuran (100 mL) and water (16 mL) was added 10% palladium on carbon (800 mg). The reaction was stirred vigorously under one atmosphere of hydrogen for 6.5 h. The solids were filtered off and washed with tetrahydrofuran (4×25 mL) and then 50% methanol/tetrahydrofuran (2×25 mL). The combined filtrates were evaporated to dryness and the crude product was purified by reverse-phase HPLC. Fractions containing pure product were combined and lyophilized. The product from several runs was combined to give 4.68 g which was dissolved in acetonitrile (200 mL) and water (200 mL). 1.0 N HCl (18.7 mL) was added, and the solution was lyophilized. The residue was again dissolved in acetonitrile (125 mL) and water (125 mL). 1.0 N HCl was added and the solution was lyophilized to give a hydrochloride salt of compound 61 as an off white powder. 1H NMR (300 MHz, DMSO-d6) δ 10.55 (br s, 1H), 9.40 (br s, 1H), 8.80, (br s, 1H), 8.26 (d, 1H), 7.60, (br s, 2H) 7.25-7.45 (m, 5H), 6.92-7.16 (m 10H), 6.55 (d, 1H), 5.45 (d, 1H), 3.69 (s, 3H), 2.80-3.15 (m, 6H); m/z: [M+H+] calcd for C32H31N3O4 522.24. found 522.4.

Workup

  1. filtrationThe solids were filtered off
  2. washwashed with tetrahydrofuran (4×25 mL)
  3. customThe combined filtrates were evaporated to dryness
  4. customthe crude product was purified by reverse-phase HPLC
  5. additionFractions containing pure product
  6. customto give 4.68 g which

Sources & evidence

ORD record
ord-359355fa4b6b48209ada1656464334cf
Source dataset
uspto-grants-2009_09
Patent number
US07582765B2

Reaction notes

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