N-[(4aR,6R,8aS)-6-[(benzyloxy)methyl]-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide → rel-N-[(4aR,6R,8aS)-6-cyclopropyl-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 1478717Notes

Reaction equation

HRID 1478717 reaction equation
[CH:1]1([C@@H:4]2[O:9][CH2:8][C@@:7]([NH:18][C:19]([NH:21][C:22](=[O:29])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[S:20])([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=3[F:17])[C@H:6]([CH2:30]O)[CH2:5]2)[CH2:3][CH2:2]1.C(OC[C@@H]1OC[C@]2(C3C=CC(F)=CC=3F)N=C(NC(=O)C3C=CC=CC=3)SC[C@@H]2C1)C1C=CC=CC=1>>[CH:1]1([C@@H:4]2[O:9][CH2:8][C@:7]3([C:10]4[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=4[F:17])[N:18]=[C:19]([NH:21][C:22](=[O:29])[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[S:20][CH2:30][C@@H:6]3[CH2:5]2)[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 86729526N-[(4aR,6R,8aS)-6-[(benzyloxy)methyl]-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamideHCID 90253442rel-N-{[(3S,4R,6R)-6-cyclopropyl-3-(2,4-difluorophenyl)-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}benzamide

Product 1

HCID 90253443rel-N-[(4aR,6R,8aS)-6-cyclopropyl-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Procedure

rel-N-{[(3S,4R,6R)-6-Cyclopropyl-3-(2,4-difluorophenyl)-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}benzamide (C21) was converted to the product using the method described for synthesis of N-[(4aR,6R,8aS)-6-[(benzyloxy)methyl]-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C8) in Preparation P1. The product was obtained as a solid. Yield: 1.42 g, 3.31 mmol, 88%. LCMS m/z 429.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 11.7-12.5 (v br s, 1H), 8.24 (br d, J=7.6 Hz, 2H), 7.48-7.54 (m, 1H), 7.38-7.48 (m, 3H), 6.82-6.97 (m, 2H), 4.08 (br dd, J=12.4, 1.3 Hz, 1H), 3.80 (d, J=12.3 Hz, 1H), 3.05-3.13 (m, 1H), 2.93-3.04 (m, 2H), 2.64 (dd, J=12.8, 2.6 Hz, 1H), 2.05-2.18 (m, 1H), 1.75-1.83 (m, 1H), 0.96-1.06 (m, 1H), 0.50-0.62 (m, 2H), 0.40-0.46 (m, 1H), 0.22-0.29 (m, 1H).

Workup

  1. customThe product was obtained as a solid

Sources & evidence

ORD record
ord-8513147355c741a7bb87c5f6d781a34b
Source dataset
uspto-grants-2016_08
Patent number
US09403846B2

Reaction notes

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