Trifluoroacetic acid → HCID 71256036, compound

HRID 920215Notes

Reaction equation

HRID 920215 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].C(Cl)(=O)C(Cl)=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][N:36]=2)[N:19]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CN(C=O)C>[NH2:27][C:25]1[N:24]=[CH:23][N:22]=[C:21]2[N:20]([C:35]3[N: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

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65578Oxalyl chlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 71256154HCID 71256154, compound

Product 1

HCID 71256036HCID 71256036, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of (E)-4-(dimethylamino)but-2-enoic acid (5) (185 mg, 1.12 mmol) and a drop of DMF in dry DCM (3 mL) was added oxalyl dichloride (427 mg, 3.36 mmol) slowly. The mixture was stirred at room temperature for 2 h and the solvent was removed in vacuo. The freshly generated acid chloride was dissolved in dry DCM (5 mL) and was added dropwise into a solution of tert-butyl 3-iodo-1-(5-(methylamino)pyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylcarbamate (64) (400 mg, 0.86 mmol) in DCM (8 mL) at 0° C. The resulting mixture was stirred at room temperature for 3 h. TFA (2 mL) was introduced and the reaction mixture was stirred for 5 h. The solvent was removed and the residue was purified by column chromatography (silica gel, 0 to 7% methanol in dichloromethane) to provide (E)-N-(6-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyridin-3-yl)-4-(dimethylamino)-N-methylbut-2-enamide (65) (300 mg, 73%) as a white solid. LC-MS (ESI): m/z (M+1) 479.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe freshly generated acid chloride was dissolved in dry DCM (5 mL)
  3. stirringThe resulting mixture was stirred at room temperature for 3 h
  4. stirringthe reaction mixture was stirred for 5 h
  5. customThe solvent was removed
  6. customthe residue was purified by column chromatography (silica gel, 0 to 7% methanol in dichloromethane)

Sources & evidence

ORD record
ord-34fad7935ed14cfebda85e0196e76ba1
Source dataset
uspto-grants-2016_03
Patent number
US09273051B2

Reaction notes

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