(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)-4-methyl-6-[(propan-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine

HRID 1775741Notes

Reaction equation

HRID 1775741 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][CH:21]([CH3:23])[CH3:22])[CH2:15][C@H:14]1[C@@H:13]([CH3:24])[S:12][C:11]([NH:25]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][CH:21]([CH3:22])[CH3:23])[CH2:15][C@H:14]1[C@@H:13]([CH3:24])[S:12][C:11]([NH2:25])=[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 118322866N-{(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-4-methyl-6-[(propan-2-yloxy)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 73507383(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-4-methyl-6-[(propan-2-yloxy)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)-4-methyl-6-[(propan-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl}benzamide (C27) 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 isolated as a white solid. Yield: 26.6 mg, 71.8 μmol, 88%. LCMS m/z 371.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 7.32 (ddd, J=9.6, 8.6, 6.5 Hz, 1H), 6.92-7.01 (m, 2H), 4.10 (dd, J=11.1, 2.0 Hz, 1H), 3.73 (d, J=11.3 Hz, 1H), 3.7-3.77 (m, 1H), 3.67 (septet, J=6.1 Hz, 1H), 3.51 (dd, half of ABX pattern, J=10.2, 6.3 Hz, 1H), 3.45 (dd, half of ABX pattern, J=10.2, 4.2 Hz, 1H), 3.06-3.14 (m, 1H), 2.75 (ddd, J=12.2, 3.9, 3.6 Hz, 1H), 1.58-1.65 (m, 1H), 1.36-1.47 (m, 1H), 1.13-1.20 (m, 9H).

Workup

  1. customThe product was isolated as a white solid

Sources & evidence

ORD record
ord-48a7f13b84664b4d95c574a35d3c56b2
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

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