Phosphorus oxychloride → HCID 178457482, compound

HRID 2169251Notes

Reaction equation

HRID 2169251 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:30](O)=[O:31])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=3[Cl:29])[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:33]([O:40][CH2:41][CH2:42][NH:43][CH:44]([CH3:46])[CH3:45])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34].O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>N1C=CC=CC=1.CCCCCC.O.C(OCC)(=O)C>[Si:33]([O:40][CH2:41][CH2:42][N:43]([CH:44]([CH3:46])[CH3:45])[C:30]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=3[Cl:29])[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:31])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 178524875HCID 178524875, compound

Product 1

HCID 178457482HCID 178457482, compoundYield 35.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a stirred white suspension of 5-benzyloxy-2-[1-(2,5-dichlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid (205) (500 mg, 1.05 mmol) in pyridine (5.5 mL) was added [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (344 mg, 1.58 mmol), cooled to −10° C., POCl3 (0.3 mL, 3.17 mmol) was added at the same temperature. The mixture was stirred at 0° C. for 2 h. Silica thin layer chromatography was performed (50% ethyl acetate in hexane, Rf=0.8). After completion of the reaction, ice cooled-water (30 mL) was added to the reaction mixture at 0° C., a saturated solution of NaHCO3 (pH˜8) was added, the mixture was extracted with ethyl acetate (4×50 mL), the organic part was dried and concentrated, the crude product was purified by a CombiFlash column (eluted at 30%-50% ethyl acetate in hexane) to get 5-benzyloxy-2-[1-(2,5-dichlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (206) (250 mg, 35.18%) as a yellow sticky mass.

Workup

  1. customAfter completion of the reaction, ice
  2. additionwas added to the reaction mixture at 0° C.
  3. extractionthe mixture was extracted with ethyl acetate (4×50 mL)
  4. customthe organic part was dried
  5. concentrationconcentrated
  6. customthe crude product was purified by a CombiFlash column (eluted at 30%-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-222f78ebd44545adb7e2e022e4626ceb
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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