N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide → (4R,4aR,6R,8aS)-2-(benzoylamino)-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylic acid

HRID 590612Notes

Reaction equation

HRID 590612 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][OH:20])[CH2:15][C@H:14]1[C@@H:13]([CH3:21])[S:12][C:11]([NH:22][C:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[N:10]2.C(NC1SC[C@@H]2C[C@H](C(O)=O)OC[C@]2(C2C=CC(F)=CC=2F)N=1)(=[O:38])C1C=CC=CC=1>>[C:23]([NH:22][C:11]1[S:12][C@H:13]([CH3:21])[C@@H:14]2[CH2:15][C@H:16]([C:19]([OH:38])=[O:20])[O:17][CH2:18][C@:9]2([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[N:10]=1)(=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

3

Reactant 2

HCID 89889267N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamideHCID 89889273(4aR,6R,8aS)-2-(Benzoylamino)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylic acid

Product 1

HCID 89889289(4R,4aR,6R,8aS)-2-(benzoylamino)-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylic acid

Procedure

The product, obtained as a pink/white solid, was prepared from N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4-methyl-4,4a, 5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (P5) according to the procedure for the synthesis of (4aR,6R,8aS)-2-(benzoylamino)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylic acid (P2) in Preparation 2. Yield: 2.92 g, 6.54 mmol, 95%. LCMS m/z 447.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.08-8.12 (m, 2H), 7.52-7.58 (m, 1H), 7.41-7.49 (m, 3H), 7.02-7.11 (m, 2H), 4.34 (dd, J=12.1, 2.7 Hz, 1H), 4.20 (br d, J=11.9 Hz, 1H), 3.98 (d, J=11.9 Hz, 1H), 3.18-3.26 (m, 1H), 3.06 (ddd, J=12.1, 3.9, 3.9 Hz, 1H), 2.15 (ddd, J=13.6, 4.0, 2.9 Hz, 1H), 1.71-1.83 (m, 1H), 1.27 (d, J=6.8 Hz, 3H).

Workup

  1. customThe product, obtained as a pink/white solid

Sources & evidence

ORD record
ord-590203498e7346a2a1b83e8006dad03a
Source dataset
uspto-grants-2016_01
Patent number
US09233981B1

Reaction notes

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