Phosphorus oxychloride → HCID 178457489, compound

HRID 2169198Notes

Reaction equation

HRID 2169198 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][NH:11][CH:12]([CH3:14])[CH3:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:15]([O:22][C:23]1[C:24]([C:40](O)=[O:41])=[N:25][C:26]([CH2:30][C:31]([CH3:39])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH3:32])=[N:27][C:28]=1[OH:29])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O=P(Cl)(Cl)Cl>O.N1C=CC=CC=1>[CH2:15]([O:22][C:23]1[C:24]([C:40]([N:11]([CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:12]([CH3:14])[CH3:13])=[O:41])=[N:25][C:26]([CH2:30][C:31]([CH3:32])([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH3:39])=[N:27][C:28]=1[OH:29])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 178441874HCID 178441874, compound

Product 1

HCID 178457489HCID 178457489, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 1049PyridineSolvent

Conditions

Temperature
-10 °C

Procedure

N-(2-(tert-Butyldimethylsilyloxy)ethyl)propan-2-amine (8b) (98.0 mg, 451 μmol, Eq: 1.1, prepared as previously described) was added to 5-(benzyloxy)-6-hydroxy-2-(2-methyl-2-phenylpropyl)pyrimidine-4-carboxylic acid (56) (155 mg, 410 μmol, Eq: 1.00), then pyridine (2.5 ml) was added, and the reaction mixture was cooled to −10° C. with stirring. POCl3 (188 mg, 115 μl, 1.23 mmol, Eq: 3) was added dropwise, then the reaction mixture was stirred at −10° C. for 1 hour, allowed to warm to 0° C. and stirred for one hour. 10 drops of water were added at 0° C., the reaction mixture was stirred for 5 min and the solvent was removed on a rotary evaporator to almost dryness. The mixture was placed on 12 g silica gel column and eluted with 5% to 50% ethyl acetate/hexane over 20 min. to give 5-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-6-hydroxy-N-isopropyl-2-(2-methyl-2-phenylpropyl)pyrimidine-4-carboxamide (57) (62 mg, 26%).

Workup

  1. stirringthe reaction mixture was stirred at −10° C. for 1 hour
  2. temperatureto warm to 0° C.
  3. stirringstirred for one hour
  4. stirringthe reaction mixture was stirred for 5 min
  5. customthe solvent was removed on a rotary evaporator to almost dryness
  6. washeluted with 5% to 50% ethyl acetate/hexane over 20 min.

Sources & evidence

ORD record
ord-089496d327ce4679ae54485838348a14
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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