Trifluoroacetic acid → HCID 59437051, compound

HRID 1640994Notes

Reaction equation

HRID 1640994 reaction equation
[NH2:1][C:2]1[CH:49]=[CH:48][C:5]([C:6]([NH:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([S:18]([C:21]4[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=4)(=[O:20])=[O:19])[CH:16]=3)[N:11](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:10]=2)=[O:7])=[C:4]([N:50]([CH:57]2[CH2:62][CH2:61][O:60][CH2:59][CH2:58]2)C(=O)C(F)(F)F)[CH:3]=1.FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C.[CH3:88][N:89]([CH3:94])[CH2:90][C:91](=O)[CH3:92]>ClCCl>[F:27][C:25]1[CH:26]=[C:21]([S:18]([C:15]2[CH:16]=[C:17]3[C:12](=[CH:13][CH:14]=2)[NH:11][N:10]=[C:9]3[NH:8][C:6](=[O:7])[C:5]2[CH:48]=[CH:49][C:2]([NH:1][CH:91]([CH3:92])[CH2:90][N:89]([CH3:94])[CH3:88])=[CH:3][C:4]=2[NH:50][CH:57]2[CH2:62][CH2:61][O:60][CH2:59][CH2:58]2)(=[O:19])=[O:20])[CH:22]=[C:23]([F:28])[CH:24]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 848831-(Dimethylamino)acetone2×HCID 13696215Tetramethylammonium Triacetoxyborohydride (>90%)2×HCID 86643845HCID 86643845, compound

Product 1

HCID 59437051HCID 59437051, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-amino-N-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-yl]-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide (1.56 g, 1.8 mmol) in dichloromethane (30 mL) was added trifluoroacetic acid (2.78 mL, 36 mmol), tetramethylammonium triacetoxyborohydride (710 mg, 2.7 mmol) and 1-dimethylamino-propan-2-one (316 microL, 2.7 mmol). The mixture was stirred at room temperature overnight then additional tetramethylammonium triacetoxyborohydride (710 mg, 2.7 mmol) and 1-dimethylamino-propan-2-one (316 microL, 2.7 mmol) were added. The mixture was heated at reflux and stirred for additional 6 hours. After evaporation of the volatiles, the residue was chromatographed on silica gel eluting with dichloromethane/methanol/triethylamine 90:10:0.1 affording 845 mg of N-[5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-4-(2-dimethylamino-1-methyl-ethylamino)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide that was dissolved in methanol (5 mL) and triethylamine (2 mL) and stirred at 50° C. for 6 hours. The mixture was then evaporated to dryness and the residue purified by flash chromatography on silica gel eluting with dichloromethane/methanol/30% NH4OH 92:8:0.5 affording 416 mg of the title compound as pale yellow solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux
  3. stirringstirred for additional 6 hours
  4. customAfter evaporation of the volatiles
  5. customthe residue was chromatographed on silica gel eluting with dichloromethane/methanol/triethylamine 90:10:0.1 affording 845 mg of N-[5-(3,5-difluoro-benzenesulfonyl)-1H-indazol-3-yl]-4-(2-dimethylamino-1-methyl-ethylamino)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide that
  6. dissolutionwas dissolved in methanol (5 mL)
  7. stirringtriethylamine (2 mL) and stirred at 50° C. for 6 hours
  8. customThe mixture was then evaporated to dryness
  9. customthe residue purified by flash chromatography on silica gel eluting with dichloromethane/methanol/30% NH4OH 92:8:0.5 affording 416 mg of the title compound as pale yellow solid

Sources & evidence

ORD record
ord-9e51b22bd54a481ea7b3508f30f4b211
Source dataset
uspto-grants-2012_02
Patent number
US08114865B2

Reaction notes

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