Diisopropylethylamine → HCID 178457474, compound

HRID 2169294Notes

Reaction equation

HRID 2169294 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:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:22][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][CH:43]([CH3:45])[CH3:44])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].CCCP(=O)=O.C(N(C(C)C)CC)(C)C>O1CCCC1.O.C(OCC)(=O)C>[Si:32]([O:39][CH2:40][CH2:41][N:42]([CH:43]([CH3:45])[CH3:44])[C:29]([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([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:30])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 1785248674-oxo-2-[(1-phenylcyclohexyl)methyl]-5-phenylmethoxy-1H-pyrimidine-6-carboxylic acid

Product 1

HCID 178457474HCID 178457474, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclohexylmethyl)-pyrimidine-4-carboxylic acid (256) (0.5 g, 1.19 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (0.78 g, 3.58 mmol) in dry tetrahydrofuran (20.0 mL) were added propylphosphonic anhydride (0.76 g, 2.39 mmol, 50% in ethyl acetate) and diisopropyl ethylamine (0.8 mL, 4.78 mmol) at room temperature and the reaction mixture was heated at 65° C. for 4 h. After completion of the reaction, the mixture was portioned between ethyl acetate and water. The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure to get a crude product which was purified by normal silica gel column chromatography (using 30% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclohexylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (257) (0.25 g, 34.0%) as a colorless liquid.

Workup

  1. customAfter completion of the reaction
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto get a crude product which
  6. customwas purified by normal silica gel column chromatography (using 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ccfc1d0ae14d469ebd265dba2d0dae95
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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