Methanol → (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

HRID 1775731Notes

Reaction equation

HRID 1775731 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][CH3:21])[CH2:15][C@H:14]1[C@@H:13]([CH3:22])[S:12][C:11]([NH:23]C(=O)C1C=CC=CC=1)=[N:10]2.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.CO>ClCCl>[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][CH3:21])[CH2:15][C@H:14]1[C@@H:13]([CH3:22])[S:12][C:11]([NH2:23])=[N:10]2

Participants

6

Reactant 4

HCID 887MethanolHCID 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 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 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-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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) 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. In this case, the chromatography was carried out using a gradient of 0% to 10% methanol in dichloromethane; the product was isolated as a white solid. Yield: 69.3 mg, 0.202 mmol, 83%. LCMS m/z 343.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 7.32 (ddd, J=9.6, 9.0, 6.6 Hz, 1H), 6.92-7.00 (m, 2H), 4.10 (dd, J=11.1, 2.2 Hz, 1H), 3.75-3.82 (m, 1H), 3.72 (d, J=11.1 Hz, 1H), 3.47 (dd, half of ABX pattern, J=10.3, 6.4 Hz, 1H), 3.41 (dd, half of ABX pattern, J=10.3, 3.9 Hz, 1H), 3.38 (s, 3H), 3.05-3.13 (m, 1H), 2.71-2.78 (m, 1H), 1.55-1.62 (m, 1H), 1.36-1.47 (m, 1H), 1.17 (d, J=6.8 Hz, 3H).

Workup

  1. customthe product was isolated as a white solid

Sources & evidence

ORD record
ord-b449fb6e83c54867adfdfe22ff264612
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

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