N,N-Diethylaniline → (R)-2-Amino-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)-6-chloropurine

HRID 458285Notes

Reaction equation

HRID 458285 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([O:15][CH2:16][CH2:17][C@@H:18]([CH2:31][O:32][C:33](=[O:51])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:19][N:20]1[CH:28]=[N:27][C:26]2[C:25](=O)[NH:24][C:23]([NH2:30])=[N:22][C:21]1=2)=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:65])=O>C(#N)C.[Cl-].C[N+](C)(C)C>[NH2:30][C:23]1[N:22]=[C:21]2[C:26]([N:27]=[CH:28][N:20]2[CH2:19][C@H:18]([CH2:31][O:32][C:33](=[O:51])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:17][CH2:16][O:15][C:13](=[O:14])[C@H:9]([CH:10]([CH3:12])[CH3:11])[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[C:25]([Cl:65])[N:24]=1

Participants

6

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 135796494(R)-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)guanine

Product 1

HCID 53751265(R)-2-Amino-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)-6-chloropurine

Reagents, catalysts & solvents 2

HCID 6379Tetramethylammonium chlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)guanine from step b of Example 1 (646 mg, 0.9 mmole) in acetonitrile were added tetramethylammonium chloride (427 mg, 2.7 mmole), N,N-diethylaniline (0.716 ml, 4.5 mmole) and phosphorous oxychloride (0.417 ml, 4.5 mmole). The reaction was kept under reflux and the progression monitored by TLC. After 3 hours the reaction mixture was evaporated in vacuo and the residue was dissolved in dichloromethane, then poured into cold sodium hydrogen carbonate aqueous solution. The organic phase was evaporated and purified by silica gel column chromatography. Yield: 251 mg.

Workup

  1. temperatureunder reflux
  2. customAfter 3 hours the reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in dichloromethane
  4. additionpoured into cold sodium hydrogen carbonate aqueous solution
  5. customThe organic phase was evaporated
  6. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-369bf042a18349c9a2c151a8fc4be02b
Source dataset
uspto-grants-2007_03
Patent number
US07189849B2

Reaction notes

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