Sodium hydride → 4-(Adamantan-1-ylmethoxy)-6-chloro-pyrimidin-2-ylamine

HRID 1499205Notes

Reaction equation

HRID 1499205 reaction equation
[C:1]12([CH2:11][OH:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C1OCCOCCOCCOCCOC1.[H-].[Na+].[Cl:30][C:31]1[CH:36]=[C:35](Cl)[N:34]=[C:33]([NH2:38])[N:32]=1>C1COCC1>[C:1]12([CH2:11][O:12][C:35]3[CH:36]=[C:31]([Cl:30])[N:32]=[C:33]([NH2:38])[N:34]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 64556Tricyclo(3.3.1.1'3,7)dec-1-ylmethanolHCID 655222-Amino-4,6-dichloropyrimidine

Product 1

HCID 1179420184-(Adamantan-1-ylmethoxy)-6-chloro-pyrimidin-2-ylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of adamantan-1-yl-methanol (100 mg, 0.60 mmol) in THF (5 mL) was cooled 15 to 0° C. 15-Crown-5 ether (99 mg, 0.5 mmol) and NaH (60% in oil, 92 mg, 2.4 mmol) were added sequentially. The reaction was warmed to RT for 1 h, cooled to 0° C., and 4,6-dichloropyrimidin-2-ylamine (247 mg, 1.5 mmol) was added. The reaction was heated to 65° C. for 16 h, cooled to RT, quenched with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (EtOAc/heptane) provided 4-(adamantan-1-ylmethoxy)-6-chloro-pyrimidin-2-ylamine as a white solid.

Workup

  1. temperaturecooled to 0° C.
  2. temperatureThe reaction was heated to 65° C. for 16 h
  3. temperaturecooled to RT
  4. customquenched with water
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by normal phase chromatography (EtOAc/heptane)

Sources & evidence

ORD record
ord-7684f52116c64f859e30f0a5a3eb32ea
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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