Dichloromethane → HCID 71479644, compound

HRID 1907426Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([F:34])=[C:15]([C@:17]34[O:25][CH2:24][CH2:23][C@H:22]3[CH2:21][S:20][C:19]([NH:26]C(=O)OC(C)(C)C)=[N:18]4)[CH:16]=2)=[O:9])=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.[Cl:42]CCl>>[NH2:26][C:19]1[S:20][CH2:21][C@@H:22]2[CH2:23][CH2:24][O:25][C@:17]2([C:15]2[CH:16]=[C:11]([NH:10][C:8](=[O:9])[C:5]3[CH:4]=[CH:3][C:2]([Cl:42])=[CH:7][N:6]=3)[CH:12]=[CH:13][C:14]=2[F:34])[N:18]=1

Participants

Reactant 3

HCID 6344Dichloromethane

HCID 6422Trifluoroacetic acid

HCID 86762145HCID 86762145, compound

Product 1

HCID 71479644HCID 71479644, compound

Procedure

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 (45 mg) in dichloromethane (0.44 mL) was added TFA (103 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-((4aR,7aR)-2-amino-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-chloropicolinamide as a white foam (29 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 (M+H)+: 453.3. Retention time: 18.96 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: 11.49 chiralcel OD-H 4.6×100 mm, flow rate: 2 mL/min) eluting with 30% B (A: 0.1% Et2NH/Heptane; B: ethanol).

Workup

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

Sources & evidence

ORD record: ord-f3a67e2b97674d30a56a4860cf85d892
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598161B2

Reaction notes

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