Triethylamine → N-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-2-chloro-5-fluoro-4-pyrimidinamine

HRID 734440Notes

Reaction equation

HRID 734440 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:9][C:10]1[N:15]=[C:14]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])[C:13]([F:21])=[CH:12][N:11]=1.C(N(CC)CC)C>ClCCl.CN(C1C=CC=CN=1)C>[Si:1]([O:20][CH2:19][CH2:18][CH2:17][NH:16][C:14]1[C:13]([F:21])=[CH:12][N:11]=[C:10]([Cl:9])[N:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 57845437HCID 57845437, compound

Product 1

HCID 57845365N-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-2-chloro-5-fluoro-4-pyrimidinamineYield 86.1%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of t-butyldimethylsilyl chloride (1.63 g, 10.70 mmol) in dichloromethane (48.63 mL) was added 3-[(2-chloro-5-fluoro-4-pyrimidinyl)amino]-1-propanol (Example 80, 2.0 g, 9.73 mmol), followed by triethylamine (1.49 mL, 10.70 mmol) and dimethylaminopyridine (0.02 g, 0.19 mmol). The resulting cloudy mixture was stirred at rt for 18 h and then diluted with dichloromethane (80 mL). The mixture was washed with water (50 mL), dried over magnesium sulfate, and concentrated. The product was purified by column chromatography (67% hexanes in EtOAc) to give the title compound as a white solid (2.68 g, 86%). 1H NMR (300 MHz, CD2Cl2) δ 7.78 (d, 1H), 3.64-3.59 (m, 2H), 3.44-3.41(m, 2H), 1.82-1.73 (m, 2H), 0.84 (s, 9H), 0.001 (s, 6H).

Workup

  1. washThe mixture was washed with water (50 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe product was purified by column chromatography (67% hexanes in EtOAc)

Sources & evidence

ORD record
ord-de3dad10817e4db3b8e57ddb30a3bf5f
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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