Trifluoroacetic acid → HCID 71256152, compound

HRID 388437Notes

Reaction equation

HRID 388437 reaction equation
[CH:1]1([N:5]([CH3:12])[CH2:6]/[CH:7]=[CH:8]/[C:9]([OH:11])=O)[CH2:4][CH2:3][CH2:2]1.C(Cl)(C(Cl)=O)=O.[I:19][C:20]1[C:28]2[C:23](=[N:24][CH:25]=[N:26][C:27]=2[NH:29]C(=O)OC(C)(C)C)[N:22]([C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([NH:43][CH3:44])[CH:38]=2)[N:21]=1.C(O)(C(F)(F)F)=O>C(#N)C.C(Cl)Cl.CN(C=O)C>[NH2:29][C:27]1[N:26]=[CH:25][N:24]=[C:23]2[N:22]([C:37]3[CH:38]=[C:39]([N:43]([CH3:44])[C:9](=[O:11])/[CH:8]=[CH:7]/[CH2:6][N:5]([CH:1]4[CH2:2][CH2:3][CH2:4]4)[CH3:12])[CH:40]=[CH:41][CH:42]=3)[N:21]=[C:20]([I:19])[C:28]=12

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65578Oxalyl chlorideHCID 71209049(2E)-4-(Cyclobutylmethylamino)-2-butenoic acidHCID 71256053HCID 71256053, compound

Product 1

HCID 71256152HCID 71256152, compoundYield 107.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (E)-4-(cyclobutyl(methyl)amino)but-2-enoic acid (139 mg, 0.48 mmol) in acetonitrile (4 mL) was added a drop of DMF before introducing (COCl)2 (73 mg, 0.574 mmol). The resulting mixture was stirred at RT for 2 h. Solvent was removed in vacuo. The residue was dissolved in DCM (5 mL) and the resulting solution was slowly introduced to a pre-cooled solution of tert-butyl-3-iodo-1-(3-(methylamino)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylcarbamate (46) (186 mg, 0.4 mmol) in DCM (5 mL) dropwise. Stirring was continued at RT overnight. TFA (8 mL) was added and resulting reaction mixture was stirred at RT for additional 2 h and then concentrated in vacuo. The residue was dissolved in sat. aqueous NaHCO3. The crude product was extracted with 85% DCM/IPA (50 mL×3). The combined organic extracts were dried over Na2SO4, filtered and concentrated to provide (E)-N-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(cyclobutyl(methyl)amino)-N-methylbut-2-enamide (52) (222 mg, quant. yield) as a white solid. LC-MS (ESI): m/z (M+1) 518.1.

Workup

  1. customSolvent was removed in vacuo
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. stirringStirring
  4. waitwas continued at RT overnight
  5. customresulting
  6. customreaction mixture
  7. stirringwas stirred at RT for additional 2 h
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in sat. aqueous NaHCO3
  10. extractionThe crude product was extracted with 85% DCM/IPA (50 mL×3)
  11. dry with materialThe combined organic extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-5cc00a2cf0fb4880b927113771913d0d
Source dataset
uspto-grants-2013_02
Patent number
US08377946B1

Reaction notes

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