Hydrochloric Acid → HCID 24968869, compound

HRID 602284Notes

Reaction equation

HRID 602284 reaction equation
[C:1]([NH:5][C:6](=[O:29])[CH2:7][N:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([O:25][CH3:26])[CH:19]=2)=[CH:16][C:15]2[C:10](=[CH:11][C:12]([OH:27])=[CH:13][CH:14]=2)[C:9]1=[O:28])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:37][CH2:38][CH2:39]Cl.[NH:41]1[CH2:45][CH2:44][CH2:43][CH2:42]1.Cl>C(#N)C>[C:1]([NH:5][C:6](=[O:29])[CH2:7][N:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([O:25][CH3:26])[CH:19]=2)=[CH:16][C:15]2[C:10](=[CH:11][C:12]([O:27][CH2:37][CH2:38][CH2:39][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)=[CH:13][CH:14]=2)[C:9]1=[O:28])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 80061-Bromo-3-chloropropaneHCID 11430Potassium Carbonate2×HCID 31268PyrrolidineHCID 59684239HCID 59684239, compound

Product 1

HCID 24968869HCID 24968869, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-tert-butyl-2-[3-(4-fluoro-3-methoxyphenyl)-7-hydroxy-1-oxo-1H-isoquinolin-2-yl]acetamide (INTERMEDIATE III.1) (25 mg, 0.063 mmol) in anhydrous acetonitrile (5 mL) were added K2CO3 (26 mg, 0.189 mmol) and 1-bromo-3-chloropropane (6.2 uL, 0.63 mmol). The reaction mixture was heated at reflux temperature for 16 h. Pyrrolidine (53 uL, 0.63 mmol) and additional K2CO3 (26 mg, 0.189 mmol) were added and the reaction mixture was heated at reflux temperature for 48 h. The reaction mixture was filtered and the filtrate concentrated in vacuo. The crude residue was purified by preparative HPLC to afford N-tert-butyl-2-[3-(4-fluoro-3-methoxyphenyl)-1-oxo-7-(3-pyrrolidin-1-ylpropoxy)-1H-isoquinolin-2-yl]acetamide (EXAMPLE 15) hydrochloride salt (4.4 mg, 0.008 mmol, 13%) as an HCl salt.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux temperature for 16 h
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux temperature for 48 h
  5. filtrationThe reaction mixture was filtered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe crude residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-8e2b3305fa3548888a86818f82e3911f
Source dataset
uspto-grants-2011_03
Patent number
US07906504B2

Reaction notes

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