(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(methoxymethyl)-4-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-2-amine → (4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(ethoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine

HRID 1775738Notes

Reaction equation

HRID 1775738 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:18][O:17][C@@H:16]([CH2:19][O:20][CH2:21][CH3:22])[CH2:15][C@H:14]1[C@@H:13]([CH3:23])[S:12][C:11]([NH:24]C(=O)C1C=CC=CC=1)=[N:10]2.FC1C=C(F)C=CC=1[C@]12CO[C@@H](COC)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](COC)C[C@H]1[C@@H](C)SC(N)=N2>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:18][O:17][C@@H:16]([CH2:19][O:20][CH2:21][CH3:22])[CH2:15][C@H:14]1[C@@H:13]([CH3:23])[S:12][C:11]([NH2:24])=[N:10]2

Participants

4

Reactant 3

HCID 73507168(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(methoxymethyl)-4-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-2-amineHCID 90089502N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(ethoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamideHCID 118322867N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(methoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 73507169(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(ethoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine

Procedure

N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(ethoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C25) was deprotected using the method described for conversion of N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(methoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C20) to (4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(methoxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine (2) in Example 2. The product was obtained as a white solid. Yield: 15.0 mg, 42.1 μmol, 79%. LCMS m/z 357.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 7.32 (ddd, J=9, 9, 7 Hz, 1H), 6.92-7.01 (m, 2H), 4.11 (dd, J=11.1, 2.0 Hz, 1H), 3.74-3.82 (m, 1H), 3.73 (d, J=11.1 Hz, 1H), 3.48-3.60 (m, 3H), 3.45 (dd, half of ABX pattern, J=10.4, 4.0 Hz, 1H), 3.06-3.14 (m, 1H), 2.75 (ddd, J=12.1, 3.9, 3.7 Hz, 1H), 1.57-1.64 (m, 1H), 1.36-1.47 (m, 1H), 1.15-1.22 (m, 6H).

Workup

  1. customThe product was obtained as a white solid

Sources & evidence

ORD record
ord-e97a0f5599ae4a0ba141dabff7307eb6
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

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