Reaction #66732

Reaction equation

sodium hydride

1-benzyloxy-7-chloro-6-fluoro-isoquinoline

1-Benzyloxy-7-chloro-6-fluoro-isoquinoline

4-amino-adamantan-1-ol

→

title compound

Yield 31.2%

5-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-adamantan-2-ylamine

Yield 31.2%

Solvents

dimethyl acetamide

dimethyl acetamide

dimethyl acetamide

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   Otherwas continued at room temperature until the reaction
3. 3
   OtherThe reaction was quenched by addition of water (15 mL)
4. 4
   Extractionthe reaction mixture was extracted twice with a mixture of dichloromethane and 2-propanol (3:1)
5. 5
   OtherThe combined organic layers were evaporated
6. 6
   workup.ADDITIONwater was added
7. 7
   Otherto remove remainders of dimethyl acetamide
8. 8
   OtherThe obtained crude product
9. 9
   Otherwas purified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane)

Procedure

To a suspension of sodium hydride (60% in mineral oil, 417 mg, 10.4 mmol, 3 eq.) in dimethyl acetamide (7 mL) was added a solution of 4-amino-adamantan-1-ol (640 mg, 3.82 mmol, 1.1 eq.) in dimethyl acetamide (7 mL). After stirring for 60 min at room temperature, a solution of 1-benzyloxy-7-chloro-6-fluoro-isoquinoline (1, 1.0 g, 3.48 mmol) in dimethyl acetamide (7 mL) was added and stirring was continued at room temperature until the reaction went to completion. The reaction was quenched by addition of water (15 mL) and the reaction mixture was extracted twice with a mixture of dichloromethane and 2-propanol (3:1). The combined organic layers were evaporated, water was added and the mixture was subjected to lyophilization to remove remainders of dimethyl acetamide. The obtained crude product was purified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane) to yield 473 mg of the title compound as diastereomeric mixture. Rt=1.35 min, 1.55 min (Method 3). Detected mass: 435.2 (M+H+).

Source