Methanol → HCID 59226040, compound

HRID 2370285Notes

Reaction equation

HRID 2370285 reaction equation
[C:1]([O:5][C:6](=[O:40])[NH:7][C:8]1([CH2:36][CH2:37][CH2:38][OH:39])[CH2:15][CH2:14][CH2:13][CH:12]([O:16][C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][C:26]=2[Cl:27])[C:23]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[N:22][CH:21]=[CH:20]3)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:44].CO>C1COCC1>[C:1]([O:5][C:6](=[O:40])[NH:7][C:8]1([CH2:36][CH2:37][CH2:38][O:39][CH3:44])[CH2:9][CH2:10][CH2:11][CH:12]([O:16][C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][C:26]=2[Cl:27])[C:23]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[N:22][CH:21]=[CH:20]3)[CH2:13][CH2:14][CH2:15]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887MethanolHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59226062HCID 59226062, compound

Product 1

HCID 59226040HCID 59226040, compoundYield 47.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 405 mg (0.71 mmol) of [5-(1-benzyloxy-7-chloro-isoquinolin-6-yloxy)-1-(3-hydroxy-propyl)-cyclooctyl]-carbamic acid tert-butyl ester (59) in 5 mL of THF was dropped into a suspension of 31.3 mg (0.78 mmol) of sodium hydride (60%) in 5 mL THF at 0° C. 88.6 μL (1.42 mmol) of iodomethane were added, and after stirring for 1 h at room temperature another 88.6 μL (1.42 mmol). The reaction mixture was stirred at room temperature until LCMS indicated complete conversion, then 5 mL of methanol were added and the volatiles removed in vacuo. The crude material was purified by silica gel chromatography. 196 mg of [5-(1-benzyloxy-7-chloro-isoquinolin-6-yloxy)-1-(3-methoxy-propyl)-cyclooctyl]-carbamic acid tert-butyl ester (61) as diastereomeric mixture could be isolated. Rt=1.89 min, 2.02 min (Method I). Detected mass: 583.3 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at room temperature until LCMS
  2. customthe volatiles removed in vacuo
  3. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6a432a523f9d4badb3bbbcfa3e2a4eed
Source dataset
uspto-grants-2014_04
Patent number
US08710077B2

Reaction notes

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