Trifluoroacetic acid → 4-[(azetidin-3-ylmethyl)amino]-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide

HRID 571938Notes

Reaction equation

HRID 571938 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:44]=[C:45]([F:47])[CH:46]=1)[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:15][C:16]([C:18]1[CH:23]=[CH:22][C:21]([NH:24][CH2:25][CH:26]2[CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]2)=[CH:20][C:19]=1[NH:37][CH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1)=[O:17].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:28]1[CH2:27][CH:26]([CH2:25][NH:24][C:21]2[CH:22]=[CH:23][C:18]([C:16]([NH:15][C:9]3[C:8]4[C:12](=[CH:13][CH:14]=[C:6]([CH2:5][C:4]5[CH:44]=[C:45]([F:47])[CH:46]=[C:2]([F:1])[CH:3]=5)[CH:7]=4)[NH:11][N:10]=3)=[O:17])=[C:19]([NH:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH:20]=2)[CH2:29]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68671777tert-butyl 3-({[4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-(tetrahydro-2H-pyran-4-ylamino)phenyl]amino}methyl)azetidine-1-carboxylate

Product 1

HCID 595773424-[(azetidin-3-ylmethyl)amino]-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamideYield 24.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

tert-butyl 3-({[4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-(tetrahydro-2H-pyran-4-ylamino)phenyl]amino}methyl)azetidine-1-carboxylate (738 mg, 1.1 mmol) was dissolved in DCM (12 mL) and TFA (3 mL) was added. The resulting reaction solution was stirred for 3 hours at room temperature. The mixture was diluted with DCM and extracted with 10% acqueous NH3. Acqueous phase was extracted several time with DCM. Collected organic phases were washed with brine, dried over sodium sulfate and evaporated to dryness. Column chromatography purification on silica gel using dichloromethane/methanol/NH3 5N in MeOH 70:30:1 as the eluant, afforded 150 mg of the title compound.

Workup

  1. customThe resulting reaction solution
  2. extractionextracted with 10% acqueous NH3
  3. extractionAcqueous phase was extracted several time with DCM
  4. washCollected organic phases were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated to dryness
  7. customColumn chromatography purification on silica gel

Sources & evidence

ORD record
ord-d76a1152f78d4b3685d8ef77636fd923
Source dataset
uspto-grants-2015_05
Patent number
US09029356B2

Reaction notes

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