Pyridine → HCID 178457486, compound

HRID 2169410Notes

Reaction equation

HRID 2169410 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:25]([OH:27])=O)=[N:11][C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Br:24])=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:28]([O:35][CH2:36][CH2:37][NH:38][CH:39]([CH3:41])[CH3:40])([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].N1C=CC=CC=1.O=P(Cl)(Cl)Cl>O1CCCC1.CN(C)C=O.CCCCCC.C(OCC)(=O)C>[Si:28]([O:35][CH2:36][CH2:37][N:38]([CH:39]([CH3:41])[CH3:40])[C:25]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Br:24])[N:11]=1)=[O:27])([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]

Participants

9

Reactant 4

HCID 1049PyridineHCID 24813Phosphorus oxychlorideHCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 178524880HCID 178524880, compound

Product 1

HCID 178457486HCID 178457486, compoundYield 50.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 5-benzyloxy-2-(2-bromo-4-chlorobenzyl)-6-hydroxypyrimidine-4-carboxylic acid (377) (4.0 g, 8.9 mmol) in tetrahydrofuran (150 mL) was added [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (5.8 g, 26.73 mmol). To the reaction mixture, pyridine (2.159 mL, 26.726 mmol) was added, followed very slow addition of POCl3 (2.454 mL, 26.726 mmol) at −15° C. the resulting reaction mixture was stirred for 2 h at same temperature. 2 drops of dimethylformamide were added to the reaction mixture which was thereafter allowed to stir at room temperature for 16 h while silica thin layer chromatography was performed (50% ethyl acetate in hexane; Rf=0.5). After completion of the reaction, the reaction mixture was quenched with ice cold water (150 mL) and extracted with ethyl acetate (2×250 mL). The combined organic parts were dried and concentrated and the resulting crude residue was purified on a column (normal silica 100-200 mesh) to get 5-benzyloxy-2-(2-bromo-4-chlorobenzyl)-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (378) (2.9 g, 50.15%) as a colorless gummy liquid.

Workup

  1. customthe resulting reaction mixture
  2. stirringto stir at room temperature for 16 h while silica thin layer chromatography
  3. customAfter completion of the reaction
  4. customthe reaction mixture was quenched with ice cold water (150 mL)
  5. extractionextracted with ethyl acetate (2×250 mL)
  6. customThe combined organic parts were dried
  7. concentrationconcentrated
  8. customthe resulting crude residue was purified on a column (normal silica 100-200 mesh)

Sources & evidence

ORD record
ord-266f0435fb2442cfa8255553e9b9caa7
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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