Diethyl Ether → 5'-(7-Acetylimidazo[1,2-alpha]pyrimidin-3-yl)-2'-fluorobiphenyl-2-carbonitrile

HRID 2183870Notes

Reaction equation

HRID 2183870 reaction equation
C[O:2][C:3]([C:7]1[CH:12]=[CH:11][N:10]2[C:13]([C:16]3[CH:17]=[CH:18][C:19]([F:30])=[C:20]([C:22]4[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH:21]=3)=[CH:14][N:15]=[C:9]2[N:8]=1)(OC)[CH3:4].C(=O)([O-])O.[Na+].C(OCC)C>Cl>[C:3]([C:7]1[CH:12]=[CH:11][N:10]2[C:13]([C:16]3[CH:17]=[CH:18][C:19]([F:30])=[C:20]([C:22]4[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH:21]=3)=[CH:14][N:15]=[C:9]2[N:8]=1)(=[O:2])[CH3:4]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 697089515'-[7-(1,1-Dimethoxyethyl)imidazo[1,2-alpha]pyrimidin-3-yl]-2'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 101551885'-(7-Acetylimidazo[1,2-alpha]pyrimidin-3-yl)-2'-fluorobiphenyl-2-carbonitrileYield 77%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of crude 5′-[7-(1,1-dimethoxyethyl)imidazo[1,2-α]pyrimidin-3-yl]-2′-fluorobiphenyl-2-carbonitrile (1.21 g) in 2.5N hydrochloric acid (40 ml) was stirred at 50° C. for 15 h. After cooling to ambient temperature the mixture was made neutral with solid sodium hydrogencarbonate, added portionwise over 15 min. The aqueous was extracted with 2% methanol in dichloromethane (2×75 ml), the organics combined, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica, eluting with dichloromethane (+0.5% triethylamine) on a gradient of methanol (1-5%) gave a solid. Trituration with diethyl ether afforded 5′-(7-acetylimidazo[1,2-α]pyrimidin-3-yl)-2′-fluorobiphenyl-2-carbonitrile (0.82 g, 77%) as a yellow solid: δH (360 MHz, CDCl3) 2.83 (3H, s), 7.44 (1H, t, J 9), 7.53-7.74 (6H, m), 7.87 (1H, dd, J 8 and 1), 8.12 (1H, s), 8.92 (1H, d, J 7); m/z (ES+) 357 (M++H).

Workup

  1. temperatureAfter cooling to ambient temperature the mixture
  2. additionadded portionwise over 15 min
  3. extractionThe aqueous was extracted with 2% methanol in dichloromethane (2×75 ml)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered and pre-adsorbed onto silica
  6. customPurification by chromatography on silica
  7. washeluting with dichloromethane (+0.5% triethylamine) on a gradient of methanol (1-5%)
  8. customgave a solid

Sources & evidence

ORD record
ord-138500fab27b40959c9f2460285b2b24
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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