Diisopropylethylamine → 3-Bromo-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-alpha]pyrimidine

HRID 2184004Notes

Reaction equation

HRID 2184004 reaction equation
FC(F)(F)S([O:6][Si:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9])(=O)=O.[Br:16][C:17]1[N:21]2[CH:22]=[CH:23][C:24]([C:26](O)([CH3:28])[CH3:27])=[N:25][C:20]2=[N:19][CH:18]=1.C(N(CC)C(C)C)(C)C>ClCCl>[Br:16][C:17]1[N:21]2[CH:22]=[CH:23][C:24]([C:26]([CH3:28])([O:6][Si:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9])[CH3:27])=[N:25][C:20]2=[N:19][CH:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2733308Triethylsilyl trifluoromethanesulphonateHCID 112422822-(3-Bromoimidazo[1,2-a]pyrimidin-7-yl)propan-2-ol

Product 1

HCID 695598483-Bromo-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-alpha]pyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

Triethylsilyl trifluoromethanesulfonate (4.85 ml, 21.5 mmol) was added dropwise over 15 min to a cooled (−50° C.) solution of 2-(3-bromoimidazo[1,2-α]pyrimidin-7-yl)propan-2-ol (5.0 g, 19.5 mmol) and N,N-diisopropylethylamine (4.76 ml, 27.5 mmol) in dichloromethane (150 ml). The mixture was stirred at −50° C. for 20 min then allowed to warm to ambient temperature over 10 h. The reaction mixture was diluted with dichloromethane (100 ml) and washed with 1N hydrochloric acid (100 ml) and water (100 ml), dried over anhydrous magnesium sulfate, filtered and evaporated. The resulting red oil was purified by dry flash column chromatography on silica eluting with dichloromethane on a gradient of methanol (0-3%) to give 3-bromo-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-α]pyrimidine as a pale yellow oil which crystallised on standing (6.21 g, 86%): δH (400 MHz, CDCl3) 0.64 (6H, q, J 8), 0.97 (9H, t, J 8), 7.50 (1H, d, J 7), 7.72 (1H, s), 8.35 (1H, d, J 7), 10.36 (1H, d, J 7); m/z (ES+) 358 (M++H).

Workup

  1. temperatureto warm to ambient temperature over 10 h
  2. washwashed with 1N hydrochloric acid (100 ml) and water (100 ml)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe resulting red oil was purified
  7. dry with materialby dry flash column chromatography on silica eluting with dichloromethane on a gradient of methanol (0-3%)

Sources & evidence

ORD record
ord-accfb6df3ec84c2d993e4838577bd4f1
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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