Trifluoroacetic acid → Trifluoroacetic acid

HRID 1529353Notes

Reaction equation

HRID 1529353 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14](C1CCCCO1)[N:13]=[C:12]2[C:24]1[N:29]=[C:28]([O:30][C@H:31]2[CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36][CH2:35][C:32]32[CH2:34][CH2:33]3)[CH:27]=[N:26][CH:25]=1.[C:46]([OH:52])([C:48]([F:51])([F:50])[F:49])=[O:47]>C(Cl)Cl>[CH2:34]1[C:32]2([CH2:35][CH2:36][NH:37][CH2:38][C@@H:31]2[O:30][C:28]2[N:29]=[C:24]([C:12]3[C:11]4[C:15](=[CH:16][CH:17]=[C:9]([C:3]5[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=5[F:1])[CH:10]=4)[NH:14][N:13]=3)[CH:25]=[N:26][CH:27]=2)[CH2:33]1.[C:46]([OH:52])([C:48]([F:51])([F:50])[F:49])=[O:47]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67959729HCID 67959729, compound

Product 2

HCID 6422Trifluoroacetic acidYield 55.3%HCID 67960061HCID 67960061, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4R)-tert-butyl 4-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (0.983 g, 1.591 mmol) in 8 mL DCM was added TFA (3.68 mL, 47.7 mmol). After 6 h at RT, the orange reaction was placed in the freezer overnight, and in the morning was warmed and stirred at RT for 3 h. The reaction was concentrated in vacuo, then taken up in DMSO (6 mL total), filtered, and purified by RPHPLC, 20-70% ACN/H2O with 0.1% TFA; product-containing fractions were combined and concentrated in vacuo to give (R)-3-(6-(6-azaspiro[2.5]octan-4-yloxy)pyrazin-2-yl)-5-(2,6-difluorophenyl)-1H-indazole*1.5 TFA (0.530 g, 0.88 mmol, 55% yield) yellow solid: MS (ESI, pos. ion) m/z: 434 (M+1).

Workup

  1. customthe orange reaction
  2. customwas placed in the freezer overnight
  3. temperaturein the morning was warmed
  4. concentrationThe reaction was concentrated in vacuo
  5. filtrationfiltered
  6. custompurified by RPHPLC, 20-70% ACN/H2O with 0.1% TFA
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ebcc140ade1846b18ed02321e0fea3af
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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