Dichloromethane → HCID 59301408, compound

HRID 2236244Notes

Reaction equation

HRID 2236244 reaction equation
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19](Cl)(=O)[C:20](Cl)=O.C1([C:30]2[C:31]([NH2:37])=[N:32][CH:33]=[C:34]([NH2:36])[CH:35]=2)CCCC1.C(N([CH2:43][CH3:44])CC)C.[CH2:45](Cl)Cl>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH:20]1([NH:37][C:31]2[N:32]=[CH:33][C:34]([NH:36][C:12]([C:10]3[N:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:8][C:9]=3[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:35][CH:30]=2)[CH2:19][CH2:44][CH2:43][CH2:45]1

Participants

8

Reactant 5

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 67534764HCID 67534764, compound

Product 1

HCID 59301408HCID 59301408, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acid (454 mg, 1.77 mmol), CH2Cl2 (5 mL), and a catalytic amount of DMF was stirred under Ar, cooled in an ice bath, and oxalyl chloride (308 μL, 3.53 mmol) was added dropwise into the mixture over 5 min. The mixture was immediately allowed to warm to room temperature and after 1.5 hr the reaction was concentrated to dryness. Dichloromethane was added and the solution was evaporated to dryness again. The white-yellow solid was re-dissolved in 5 mL of CH2Cl2 and added dropwise, under Ar, into a 0° C. solution of cyclopentyl-pyridine-2,5-diamine (448 mg, 2.53 mmol), a catalytic amount of DMAP and triethylamine (602 μL, 4.33 mmol) in 5 mL of CH2Cl2. The reaction was allowed to warm to room temperature overnight then concentrated and the residue was supported onto silica gel, and purified by flash chromatography using the Analogix system with a 40 g Redisep silica gel column with increasing concentrations of EtOAc in hexane (40 mL/min, equilibrate with 0%, 0-5 min: 0%, 5-25 min: 0 to 30%, 25-40 min: 30%). The product was triturated with hexanes six times and a 10% ether hexane four times, 20 mL total, to afford the product, 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (6-cyclopentylamino-pyridin-3-yl)-amide, as an off white solid (315 mg, 50% yield). LCMS for C21H19F3N4O2 calcd. (m/e) 416, observed 417 (M+H).

Workup

  1. temperaturecooled in an ice bath
  2. concentrationwas concentrated to dryness
  3. additionDichloromethane was added
  4. customthe solution was evaporated to dryness again
  5. dissolutionThe white-yellow solid was re-dissolved in 5 mL of CH2Cl2
  6. temperatureto warm to room temperature overnight
  7. concentrationthen concentrated
  8. custompurified by flash chromatography
  9. temperaturewith increasing concentrations of EtOAc in hexane (40 mL/min, equilibrate with 0%, 0-5 min: 0%, 5-25 min: 0 to 30%, 25-40 min: 30%)
  10. customThe product was triturated with hexanes six times

Sources & evidence

ORD record
ord-3a537d7bfbf043e7848a2b434e3e24ba
Source dataset
uspto-grants-2010_05
Patent number
US07714126B2

Reaction notes

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