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 → HCID 90253445, compound

HRID 1478763Notes

Reaction equation

HRID 1478763 reaction equation
[CH:1]1([CH2:4][C@@H:5]2[O:10][CH2:9][C@@:8]([NH:19][C:20]([NH:22][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[S:21])([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])[C@H:7]([CH2:31]O)[CH2:6]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([CH2:4][C@@H:5]2[O:10][CH2:9][C@:8]3([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=4[F:18])[N:19]=[C:20]([NH:22][C:23](=[O:30])[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[S:21][CH2:31][C@@H:7]3[CH2:6]2)[CH2:3][CH2:2]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 90253444HCID 90253444, compound

Product 1

HCID 90253445HCID 90253445, compound

Procedure

rel-N-{[(3S,4R,6S)-6-(Cyclopropylmethyl)-3-(2,4-difluorophenyl)-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}benzamide (C72) 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 white solid. Yield: 430 mg, 0.97 mmol, 39%. LCMS m/z 443 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.22 (br d, J=7.2 Hz, 2H), 7.50 (t, J=7.2 Hz, 1H), 7.37-7.45 (m, 3H), 6.85-6.94 (m, 2H), 4.13 (q, J=8.5 Hz, 1H), 3.77 (d, J=12.0 Hz, 1H), 3.67-3.73 (m, 1H), 3.10-3.17 (m, 1H), 3.00 (dd, J=12.8, 3.0, 1H), 2.64 (dd, J=12.8, 2.8 Hz, 1H), 1.93 (q, J=12.4 Hz, 1H), 1.67-1.77 (m, 2H), 0.84-0.90 (m, 1H), 0.72-0.82 (m, 1H), 0.41-0.48 (m, 2H), 0.04-0.12 (m, 2H).

Workup

  1. customThe product was obtained as a white solid

Sources & evidence

ORD record
ord-c1e9801f438e461dbf42b1d7415fcaaa
Source dataset
uspto-grants-2016_08
Patent number
US09403846B2

Reaction notes

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