Triethylamine → HCID 59684267, compound

HRID 602282Notes

Reaction equation

HRID 602282 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:25][C:26]([NH:28][CH:29]([CH3:31])[CH3:30])=[O:27])[C:10](=[O:24])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([O:18][CH2:19][C@@H:20]([CH3:23])[CH2:21][OH:22])[CH:12]=3)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:25][C:26](=[O:27])[NH:28][CH:29]([CH3:31])[CH3:30])[C:10](=[O:24])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([O:18][CH2:19][C@@H:20]([CH3:23])[CH2:21][O:22][S:40]([CH3:39])(=[O:42])=[O:41])[CH:12]=3)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chloride2×HCID 596842512-[3-(3-chlorophenyl)-7-((S)-3-hydroxy-2-methylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide

Product 1

HCID 59684267HCID 59684267, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 2-[3-(3-chlorophenyl)-7-((S)-3-hydroxy-2-methylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (319 mg, 0.720 mmol) and triethylamine (0.30 mL, 2.16 mmol) in dry DCM (7.0 mL) was cooled to 0° C. and methanesulfonyl chloride (67 μL, 0.86 mmol) was added dropwise via a syringe. The mixture was stirred for 1 h at 0° C., a second aliquot of methanesulfonyl chloride (25 μL, 0.32 mmol) was added, and stirring was continued 30 min at room temperature. The mixture was diluted with ethyl acetate (20 mL) and washed with 1 N HCl (aq.) (20 mL), sat. NaHCO3 (aq.) (20 mL) and brine (20 mL). The aqueous washes were back-extracted with ethyl acetate (20 mL), and the combined organic extracts were dried (MgSO4) and concentrated to give crude methanesulfonic acid (R)-3-[3-(3-chlorophenyl)-2-(isopropylcarbamoylmethyl)-1-oxo-1,2-dihydroisoquinolin-7-yloxy]-2-methylpropyl ester (316 mg, 0.720 mmol, 84%) as off-white solid.

Workup

  1. stirringstirring
  2. waitwas continued 30 min at room temperature
  3. washwashed with 1 N HCl (aq.) (20 mL), sat. NaHCO3 (aq.) (20 mL) and brine (20 mL)
  4. extractionThe aqueous washes were back-extracted with ethyl acetate (20 mL)
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4f2fea58f4b34167995ae27975e3ef1e
Source dataset
uspto-grants-2011_03
Patent number
US07906504B2

Reaction notes

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