Triethylamine → 3,3,3-trifluoro-N-methyl-N-[[5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.5]octan-8-yl]sulfonyl]propanamide

HRID 589978Notes

Reaction equation

HRID 589978 reaction equation
[F:1][C:2]([F:8])([F:7])[CH2:3][C:4](O)=[O:5].C(Cl)(=O)C(Cl)=O.C(OC([N:22]1[C:26]2[N:27]=[CH:28][N:29]=[C:30]([N:31]3[CH2:38][C:35]4([CH2:37][CH2:36]4)[N:34]([S:39](=[O:43])(=[O:42])[NH:40][CH3:41])[CH2:33][CH2:32]3)[C:25]=2[CH:24]=[CH:23]1)=O)(C)(C)C.CCN(CC)CC>C(Cl)Cl.O.CN(C=O)C>[F:1][C:2]([F:8])([F:7])[CH2:3][C:4]([N:40]([CH3:41])[S:39]([N:34]1[C:35]2([CH2:37][CH2:36]2)[CH2:38][N:31]([C:30]2[C:25]3[CH:24]=[CH:23][NH:22][C:26]=3[N:27]=[CH:28][N:29]=2)[CH2:32][CH2:33]1)(=[O:42])=[O:43])=[O:5]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27779723,3,3-Trifluoropropionic acidHCID 682959194-(4-Methylsulfamoyl-4,7-diaza-spiro[2.5]oct-7-yl)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester

Product 1

HCID 574114103,3,3-trifluoro-N-methyl-N-[[5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.5]octan-8-yl]sulfonyl]propanamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

3,3,3-trifluoropropanoic acid (0.24 mmol) was dissolved in dry DCM (0.5 mL) in a 4 mL vial, added oxalyl chloride (0.24 mmol) and a catalytic amount of DMF. Stirred at rt for 1 h and added to a mixture of intermediate 4 (0.05 mmol) and Et3N (0.47 mmol) in dry DCM (0.5 mL). Stirred at rt for 16 h. Reaction mixture filtered through a syringe filter, added TFA (1 mL) and stirred at rt for 15 min. Reaction mixture added H2O (5 mL) and extracted with DCM (3×5 mL). The organic phase was dried (Na2SO4), filtered, concentrated in vacuo and redissolved in DMSO (1 mL). The pure compound was obtained by standard preparative HPLC purification.

Workup

  1. stirringStirred at rt for 16 h
  2. customReaction mixture
  3. filtrationfiltered through a syringe
  4. filtrationfilter
  5. additionadded TFA (1 mL)
  6. stirringstirred at rt for 15 min
  7. customReaction mixture
  8. extractionextracted with DCM (3×5 mL)
  9. dry with materialThe organic phase was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. dissolutionredissolved in DMSO (1 mL)
  13. customThe pure compound was obtained by standard preparative HPLC purification

Sources & evidence

ORD record
ord-55de59ea82b7494cbb9892780d8c35da
Source dataset
uspto-grants-2016_01
Patent number
US09233964B2

Reaction notes

Loading…