Trifluoroacetic acid → HCID 71256087, compound

HRID 388433Notes

Reaction equation

HRID 388433 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].C(Cl)(C(Cl)=O)=O.[I:17][C:18]1[C:26]2[C:21](=[N:22][CH:23]=[N:24][C:25]=2[NH:27]C(=O)OC(C)(C)C)[N:20]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][CH3:42])=[CH:37][CH:36]=2)[N:19]=1.C(O)(C(F)(F)F)=O>C(#N)C.CN(C=O)C.C(Cl)Cl>[NH2:27][C:25]1[N:24]=[CH:23][N:22]=[C:21]2[N:20]([C:35]3[CH:36]=[CH:37][C:38]([N:41]([CH3:42])[C:7](=[O:8])/[CH:6]=[CH:5]/[CH2:4][N:3]([CH3:10])[CH3:2])=[CH:39][CH:40]=3)[N:19]=[C:18]([I:17])[C:26]=12

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65578Oxalyl chlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 71256048HCID 71256048, compound

Product 1

HCID 71256087HCID 71256087, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt (5) (66 mg, 0.4 mmol) in acetonitrile (5 mL) was added 1 drop of DMF before introducing (COCl)2 (66 mg, 0.52 mmol). The resulting mixture was stirred at RT for 2 h and then concentrated. The residue was dissolved in DCM (2 mL) before adding a solution of tert-butyl 3-iodo-1-(4-(methylamino)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylcarbamate (30) (170 mg, 0.438 mmol) in DCM (2 mL). The resulting solution was stirred at RT overnight before adding TFA (10 mL). The reaction mixture was stirred for 3 hr. The reaction mixture was concentrated and quenched with sat. aqueous NaHCO3. The mixture was extracted with 85% DCM/IPA (3×). The organic solution was dried over Na2SO4 and concentrated to provide (E)-N-(4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide (32) (170 mg, 100%) which was used in the next step directly without purification. LC-MS (ESI): m/z (M+1) 478.3.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. stirringThe resulting solution was stirred at RT overnight
  4. stirringThe reaction mixture was stirred for 3 hr
  5. concentrationThe reaction mixture was concentrated
  6. customquenched with sat. aqueous NaHCO3
  7. extractionThe mixture was extracted with 85% DCM/IPA (3×)
  8. dry with materialThe organic solution was dried over Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-57020416e90b47f78797b26fd34768b1
Source dataset
uspto-grants-2013_02
Patent number
US08377946B1

Reaction notes

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