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

HRID 38454

Reaction equation

HRID 38454 reaction equation
[H-].[Na+].[NH2:3][CH:4]1[CH:11]2[CH2:12][C:7]3([OH:14])[CH2:8][CH:9]([CH2:13][CH:5]1[CH2:6]3)[CH2:10]2.[CH2:15]([O:22][C:23]1[C:32]2[C:27](=[CH:28][C:29](F)=[C:30]([Cl:33])[CH:31]=2)[CH:26]=[CH:25][N:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC(N(C)C)=O>[CH2:15]([O:22][C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:14][C:7]34[CH2:12][CH:11]5[CH2:10][CH:9]([CH2:13][CH:5]([CH:4]5[NH2:3])[CH2:6]3)[CH2:8]4)=[C:30]([Cl:33])[CH:31]=2)[CH:26]=[CH:25][N:24]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 28574474-Aminoadamantan-1-olHCID 598182521-Benzyloxy-7-chloro-6-fluoro-isoquinoline

Product 1

HCID 583809205-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-adamantan-2-ylamineYield 31.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

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+).

Workup

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

Sources & evidence

ORD record
ord-dc8ea993b9fc424f865103a1858c2ebc
Source dataset
uspto-grants-2013_09
Patent number
US08524737B2

Linked notes

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