Phosphorus oxychloride → HCID 178455279, compound

HRID 2169189Notes

Reaction equation

HRID 2169189 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:29](O)=[O:30])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:32]([O:39][CH2:40][CH2:41][NH:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].O=P(Cl)(Cl)Cl.C(O)CO.C(=O)=O>N1C=CC=CC=1.O>[CH2:1]([O:8][C:9]1[C:10]([C:29]([N:42]([CH2:41][CH2:40][O:39][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34])[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:30])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 21993569N-(2-((tert-butyldimethylsilyl)oxy)ethyl)anilineHCID 86601574Dry ice ethyleneglycolHCID 178524871HCID 178524871, compound

Product 1

HCID 178455279HCID 178455279, compoundYield 93.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(benzyloxy)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxypyrimidine-4-carboxylic acid (28-02) (200 mg, 456 μmol, Eq: 1.00) and N-(2-(tert-butyldimethylsilyloxy)ethyl)aniline (46) (126 mg, 501 μmol, Eq: 1.1) in pyridine (2.00 ml) was added POCl3 (210 mg, 127 pμl, 1.37 mmol, Eq: 3.00) at −10° C. (ethylene glycol-dry-ice bath), then the reaction mixture was stirred at 0° C. for 2 hr. Ice cooled water was slowly added to the reaction mixture at 0° C., the reaction mixture was extracted with ethyl acetate, the organic layer was washed with aqueous saturated NaHCO3 solution, dried (MgSO4), concentrated, and chromatographed (silica gel, gradient 5 to 30% ethyl acetate-hexane) to obtain 5-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxy-N-phenylpyrimidine-4-carboxamide (47) (colorless oil, 287 mg, 427 μmol, 93.7% yield).

Workup

  1. additionwas slowly added to the reaction mixture at 0° C.
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with aqueous saturated NaHCO3 solution
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customchromatographed (silica gel, gradient 5 to 30% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-131f681ea6bc45eb84507e0db3f5ef83
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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