4-Methylmorpholine → N-(cyclopropylmethyl)-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(2,2,2-trifluoroethyl)furan-2-carboxamide

HRID 400567Notes

Reaction equation

HRID 400567 reaction equation
[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[CH:11]=[C:12]([C:15]([OH:17])=O)[O:13][CH:14]=2)=[N:3][CH:2]=1.C1CN([P+](ON2N=[N:42][C:37]3[CH:38]=[CH:39][CH:40]=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[F:58][C:59]([F:68])([F:67])[CH2:60]NCCC1CC1>CN(C=O)C>[CH:38]1([CH2:37][N:42]([CH2:60][C:59]([F:68])([F:67])[F:58])[C:15]([C:12]2[O:13][CH:14]=[C:10]([C:4]3[C:5]4[CH:9]=[CH:8][NH:7][C:6]=4[N:1]=[CH:2][N:3]=3)[CH:11]=2)=[O:17])[CH2:39][CH2:40]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2724699PyBOPHCID 21916122N-(2,2,2-trifluoroethyl)N-2-cyclopropylethylamineHCID 576474134-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carboxylic acid

Product 1

HCID 57647258N-(cyclopropylmethyl)-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(2,2,2-trifluoroethyl)furan-2-carboxamideYield 9.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

35 mg [0.153 mMols] of 4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carboxylic acid was dissolved in 1.5 mL of DMF and stirred with 120 mg [0.22 mMols] of PyBOP, 50 μL [46 mg, 0.46 mMols] of N-methylmorpholine, and 50 mg [0.26 mMols] of N-(2,2,2-trifluoroethyl) N-2-cyclopropylethylamine overnight at ambient temperature. The solvent was removed under a nitrogen stream at 30° C. and residue dissolved in methanol with several drops of TFA to protonate the amines present. The crude material was purified via C18 silica utilizing a gradient of water/acetonitrile/TFA as an eluent 5%-95%. The product, 4 mg of a beige powder (after lyophilization of filtrates) was obtained; yield 9.5%.

Workup

  1. customThe solvent was removed under a nitrogen stream at 30° C.
  2. dissolutionresidue dissolved in methanol with several drops of TFA
  3. customThe crude material was purified via C18 silica utilizing a gradient of water/acetonitrile/TFA as an eluent 5%-95%

Sources & evidence

ORD record
ord-210a68fa9f5e467f9795ac2092510c74
Source dataset
uspto-grants-2014_06
Patent number
US08741912B2

Reaction notes

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