Trifluoroacetic acid → 5-Bromopyridine-2-carboxamide

HRID 1907425Notes

Reaction equation

HRID 1907425 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10]C2C=CC(F)=C([C@]34OCC[C@H]3CSC(NC(=O)OC(C)(C)C)=N4)C=2)=[O:9])=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH2:10])=[O:9])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86762145HCID 86762145, compound

Product 1

HCID 7351515-Bromopyridine-2-carboxamideYield 228.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (4aR,7aR)-7a-(5-(5-bromopicolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate (12 mg) in dichloromethane (0.43 mL) was added TFA (67 μL) and the reaction mixture was stirred at rt for 2 h. The reaction mixture was subjected directly to preparative TLC eluting with 90% CH2Cl2/9% MeOH/1% NH4OH to give N-(3- (4aS,7aS)-2-amino-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-bromopicolinamide as a white foam (10 mg). 1H NMR (500 MHz, CDCl3) δ 9.89 (1H, s), 8.70 (1H, d, J=2.0 Hz), 8.20 (1H, d, J=8.5 Hz), 8.06 (1H, dd, J=2.0, 8.06 Hz), 8.0 (1H, m), 7.75 (1H, m), 7.09 (1H, m), 4.13 (2H, m), 3.22 (1H, m), 3.02 (1H, m), 2.89 (1H, m), and 2.22 (2H, q, J=7.5 Hz). MS: 453.3 (M+H)+. Retention time: 22.49 chiralcel OJ-H 4.6×100 mm, flow rate: 2 mL/min) eluting with 30% B (A: 0.1% Et2NH/Heptane; B: ethanol); Retention time: 12.54 chiralcel OD-H 4.6×100 mm, flow rate: 2 mL/min) eluting with 30% B (A: 0.1% Et2NH/Heptane; B: ethanol).

Workup

  1. washeluting with 90% CH2Cl2/9% MeOH/1% NH4OH

Sources & evidence

ORD record
ord-9d2a3a3d72d148cca00255e7ef0f212f
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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