Diethyl Ether → HCID 10271181, compound

HRID 2183892Notes

Reaction equation

HRID 2183892 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:18])=[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.S([CH2:37][N+:38]#[C-:39])(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].C(OCC)C>CO.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([C:17]4[O:18][CH:39]=[N:38][CH:37]=4)=[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

7

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanideHCID 87958036HCID 87958036, compound

Product 1

HCID 10271181HCID 10271181, compoundYield 35.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

2′-Fluoro-5′-(7-formylimidazo[1,2-α]pyrimidin-3-yl)biphenyl-2-carbonitrile (100 mg), tosylmethyl isocyanide (60 mg) and potassium carbonate (40 mg) were suspended in methanol (10 ml) and heated at reflux for 90 min. The reaction was cooled, diluted with dichloromethane and filtered. The filtrate was evaporated to dryness and the residue partitioned between dichloromethane and water. The organic phase was dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by flash column chromatography on silica gel eluting with dichloromethane with 1% ammonia on a gradient of methanol (1-5%) gave a solid. Trituration with diethyl ether afforded 2′-fluoro-5′-[7-(oxazol-5-yl)imidazo[1,2-α]pyrimidin-3-yl]biphenyl-2-carbonitrile as a yellow solid (40 mg, 34%): δH (360 MHz, DMSO) 7.53 (1H, d, J 7), 7.65 (1H, s), 7.70 (1H, s), 7.81 (1H, s), 7.87-7.95 (3H, m), 8.06 (1H, d, J 8), 8.11 (1H, s), 8.20 (1H, s), 8.70 (1H, s), 9.19 (1H, d, J 7); m/z (ES+) 382 (M++H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 90 min
  3. temperatureThe reaction was cooled
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue partitioned between dichloromethane and water
  7. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  8. filtrationfiltered and pre-adsorbed onto silica
  9. customPurification by flash column chromatography on silica gel eluting with dichloromethane with 1% ammonia on a gradient of methanol (1-5%)
  10. customgave a solid

Sources & evidence

ORD record
ord-a8aebebda117409a841611e5b729a209
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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