tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-methoxyquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate → (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-methoxyquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-amine

HRID 338913Notes

Reaction equation

HRID 338913 reaction equation
[F:1][C:2]([F:40])([F:39])[C@H:3]([N:26]1[CH2:30][CH2:29][C@H:28]([NH:31]C(=O)OC(C)(C)C)[CH2:27]1)[C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([O:24][CH3:25])=[C:18]([F:23])[CH:19]=4)[N:14]=3)=[N:11][N:12]=2)[CH:9]=1>C(O)(C(F)(F)F)=O>[F:40][C:2]([F:1])([F:39])[C@H:3]([N:26]1[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]1)[C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][C:17]([O:24][CH3:25])=[C:18]([F:23])[CH:19]=4)[N:14]=3)=[N:11][N:12]=2)[CH:9]=1

Participants

3

Reactant 1

HCID 86707445tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-methoxyquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate

Product 1

HCID 70984222(S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-methoxyquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-amineYield 75%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

tert-Butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-methoxyquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (109 mg, 0.194 mmol) was stirred in TFA (3 mL) for 1 hour and then concentrated. The residue was dissolved in minimum methanol and added dropwise to a 4N HCl in ether solution. The resulting solid was filtered and dried to yield (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-methoxyquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-amine (67 mg, 74.8% yield) hydrochloride as an off-white solid. LCMS APCI (+) m/z 461 (M+H). Specific rotation: [α]20D=+1.07° (c=0.96, MeOH).

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in minimum methanol
  3. additionadded dropwise to a 4N HCl in ether solution
  4. filtrationThe resulting solid was filtered
  5. customdried

Sources & evidence

ORD record
ord-bf7143b2028c46d58c51dbd983855352
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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