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Trifluoroacetic acid → 1-(4-(1-isobutyl-8-phenyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazin-7-yl)phenyl)cyclobutanamine

HRID 1509278
Notes
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Reaction equation

HRID 1509278 reaction equation
[CH2:1]([C:5]1[N:9]2[C:10]3[CH:17]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:15]([C:24]4[CH:29]=[CH:28][C:27]([C:30]5([NH:34]C(=O)OC(C)(C)C)[CH2:33][CH2:32][CH2:31]5)=[CH:26][CH:25]=4)=[N:14][C:11]=3[O:12][CH2:13][C:8]2=[N:7][N:6]=1)[CH:2]([CH3:4])[CH3:3].C(O)(C(F)(F)F)=O>ClCCl>[CH2:1]([C:5]1[N:9]2[C:10]3[CH:17]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:15]([C:24]4[CH:25]=[CH:26][C:27]([C:30]5([NH2:34])[CH2:33][CH2:32][CH2:31]5)=[CH:28][CH:29]=4)=[N:14][C:11]=3[O:12][CH2:13][C:8]2=[N:7][N:6]=1)[CH:2]([CH3:4])[CH3:3]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86683652Tert-butyl (1-(4-(1-isobutyl-8-phenyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazin-7-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 532625671-(4-(1-isobutyl-8-phenyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazin-7-yl)phenyl)cyclobutanamineYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (1-(4-(1-isobutyl-8-phenyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazin-7-yl)phenyl)cyclobutyl)carbamate (7 mg, 0.013 mmol) was dissolved in dichloromethane (1 mL); TFA (1 ml) was added at room temperature and the resulting mixture was stirred for 30 seconds. The solution was immediately concentrated to dryness under reduced pressure. The residue was dissolved in diethyl ether (˜2 ml) and concentrated to dryness under reduced pressure three times. The residue was then slurred in diethyl ether (2 ml) and after settling the supernatant solvent removed by pipette. This was repeated three times. The residue was then slurred in n-hexanes (2 ml) and after settling the supernatant solvent was removed by pipette. This was repeated three times. The remaining solvent was removed under reduced pressure and dried to give the desired product as an off-white solid (4 mg, 68% yield). LCMS (Method D): RT=0.844 min, M+1=452. 1H-NMR (500 MHz, CD3OD) δ 8.07 (1H, s), 7.52-7.45 (2H, d), 7.44-7.40 (2H, d), 7.38-7.33 (3H, m), 7.31-7.26 (2H, m), 5.66 (2H, s), 3.11 (2H, d), 2.81-2.68 (2H, m), 2.61-2.45 (2H, m), 2.32-2.17 (1H+1H, 2 m), 2.02-1.87 (1H, m), 1.10 (6H, d).

Workup

  1. concentrationThe solution was immediately concentrated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in diethyl ether (˜2 ml)
  3. concentrationconcentrated to dryness under reduced pressure three times
  4. customremoved by pipette
  5. customwas removed by pipette
  6. customThe remaining solvent was removed under reduced pressure
  7. customdried

Sources & evidence

ORD record
ord-f6ea94d80d0e4a3492c65ff8212efc93
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09221838B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes