Hydroxylamine → HCID 136477620, compound

HRID 2183888Notes

Reaction equation

HRID 2183888 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([CH:17]=O)=[N:16][C:11]3=[N:10][CH:9]=2)=[CH:4][C:3]=1[C:19]1[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=1.[NH2:27][OH:28]>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([CH:17]=[N:27][OH:28])=[N:16][C:11]3=[N:10][CH:9]=2)=[CH:4][C:3]=1[C:19]1[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 787HydroxylamineHCID 87958036HCID 87958036, compound

Product 1

HCID 136477620HCID 136477620, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 2′-fluoro-5′-(7-formylimidazo[1,2-α]pyrimidin-3-yl)biphenyl-2-carbonitrile (260 mg, 0.8 mmol) in methanol (3 ml) was treated with hydroxylamine (0.13 ml of a 50 wt. % solution in water) then heated at 60° C. for 3 h. The reaction was cooled to 0° C., the solid collected by filtration and washed with a little cold methanol to afford 2′-fluoro-5′-[7-(hydroxyiminomethyl)imidazo[1,2-α]pyrimidin-3-yl]biphenyl-2-carbonitrile as a yellow solid. This solid was suspended in dichloromethane (5 ml), treated with 1,1′-carbonyldiimidazole (180 mg, 1.1 mmol) and triethylamine (0.31 ml, 2.3 mmol) then heated at reflux for 2 h. The reaction was cooled, diluted with dichloromethane then washed with water, brine, dried over anhydrous sodium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica gel eluting with dichloromethane/methanol/conc. ammonia (99:0.9:0.1) afforded a solid which was recrystallised from acetonitrile to furnish 3-(2′-cyano-6-fluorobiphenyl-3-yl)imidazo[1,2-α]pyrimidine-7-carbonitrile as a yellow powder (160 mg, 63% over 2 steps): δH (400 MHz, DMSO) 7.64-7.72 (3H, m), 7.78-7.81 (1H, m), 7.89 (1H, ddd, J 7, 7 and 1), 7.94-7.99 (2H, m), 8.05 (1H dd, J 8 and 2), 8.43 (1H, s), 9.36 (1H, d, J 7); m/z (ES+) 340 (M++H).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. filtrationthe solid collected by filtration
  3. washwashed with a little cold methanol

Sources & evidence

ORD record
ord-9a69c4fa8433476d97f367ceb25f08ef
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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