5-[(4aR,6R,8aS)-2-amino-6-[(benzyloxy)methyl]-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile → 5-[(4aR,6R,8aS)-2-amino-6-(hydroxymethyl)-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile

HRID 68397Notes

Reaction equation

[C:1]([C:3]1[C:4]([F:31])=[CH:5][C:6]([F:30])=[C:7]([C:9]23[CH2:18][O:17][C@@H:16]([CH2:19][OH:20])[CH2:15][CH:14]2[CH2:13][S:12][C:11]([NH:21]C(=O)C2C=CC=CC=2)=[N:10]3)[CH:8]=1)#[N:2].NC1SC[C@@H]2C[C@H](COCC3C=CC=CC=3)OC[C@]2(C2C(F)=CC(F)=C(C=2)C#N)N=1>>[NH2:21][C:11]1[S:12][CH2:13][C@@H:14]2[CH2:15][C@H:16]([CH2:19][OH:20])[O:17][CH2:18][C@:9]2([C:7]2[C:6]([F:30])=[CH:5][C:4]([F:31])=[C:3]([CH:8]=2)[C:1]#[N:2])[N:10]=1

Participants

Reactant 2

HCID 762815815-[(4aR,6R,8aS)-2-amino-6-[(benzyloxy)methyl]-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile

HCID 86762637N-[(6R)-8a-(5-Cyano-2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 762818465-[(4aR,6R,8aS)-2-amino-6-(hydroxymethyl)-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile

Procedure

N-[(6R)-8a-(5-Cyano-2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C11) was converted to the product using the method described for the synthesis of 5-[(4aR,6R,8aS)-2-amino-6-[(benzyloxy)methyl]-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile (2) in Example 2. Yield: 14.2 mg, 0.042 mmol, 62%. LCMS m/z 340.1 [M+H+]. 1H NMR (400 MHz, CD3OD), δ 7.64 (t, J=7.9 Hz, 1H), 7.30 (dd, J=12.1, 9.2 Hz, 1H), 4.02 (dd, J=11.1, 2.5 Hz, 1H), 3.64-3.70 (m, 2H), 3.50-3.58 (m, 2H), 2.85-2.93 (m, 2H), 2.68-2.72 (m, 1H), 1.68-1.78 (m, 1H), 1.50-1.55 (m, 1H).

Sources & evidence

ORD record: ord-e0fe0f9241e742f0ab12cd4fc34354b9
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822456B2

Reaction notes

Loading…