(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(fluoromethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine → CID 73507165

HRID 1775736Notes

Reaction equation

HRID 1775736 reaction equation
[F:1][CH:2]([F:30])[C@@H:3]1[O:21][CH2:20][C@:6]2([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])[N:7]=[C:8]([NH:11]C(=O)C3C=CC=CC=3)[S:9][CH2:10][C@@H:5]2[CH2:4]1.FC1C=C(F)C=CC=1[C@]12CO[C@@H](CF)C[C@H]1[C@@H](C)SC(NC(=O)C1C=CC=CC=1)=N2.FC1C=C(F)C=CC=1[C@]12CO[C@@H](CF)C[C@H]1[C@@H](C)SC(N)=N2>>[F:30][CH:2]([F:1])[C@@H:3]1[O:21][CH2:20][C@:6]2([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])[N:7]=[C:8]([NH2:11])[S:9][CH2:10][C@@H:5]2[CH2:4]1

Participants

4

Reactant 3

HCID 73507166(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(fluoromethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amineHCID 90089501N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(fluoromethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamideHCID 90089532N-[(4aR,6R,8aS)-6-(Difluoromethyl)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 73507165CID 73507165

Procedure

N-[(4aR,6R,8aS)-6-(Difluoromethyl)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C24) was deprotected using the method described for conversion of N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(fluoromethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C19) to (4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(fluoromethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine (1) in Example 1; the product was isolated as a white solid. Yield: 1.46 g, 4.36 mmol, 96%. LCMS m/z 335.1 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 7.35 (ddd, J=9, 9, 7 Hz, 1H), 6.93-7.01 (m, 2H), 5.77 (td, J=55.6, 3.9 Hz, 1H), 4.11 (dd, J=11.1, 2.0 Hz, 1H), 3.81-3.92 (m, 1H), 3.73 (d, J=11.0 Hz, 1H), 2.87-2.97 (m, 2H), 2.69-2.75 (m, 1H), 1.88-1.99 (m, 1H), 1.59-1.66 (m, 1H).

Workup

  1. customthe product was isolated as a white solid

Sources & evidence

ORD record
ord-a7a6481c19a9494c9dcd01fd2bb52256
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

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