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-(methoxymethyl)-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile

HRID 1496745Notes

Reaction equation

HRID 1496745 reaction equation
[C:1]([C:3]1[C:4]([F:32])=[CH:5][C:6]([F:31])=[C:7]([C@:9]23[CH2:18][O:17][C@@H:16]([CH2:19][O:20][CH3:21])[CH2:15][C@H:14]2[CH2:13][S:12][C:11]([NH:22]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>>[NH2:22][C:11]1[S:12][CH2:13][C@@H:14]2[CH2:15][C@H:16]([CH2:19][O:20][CH3:21])[O:17][CH2:18][C@:9]2([C:7]2[C:6]([F:31])=[CH:5][C:4]([F:32])=[C:3]([CH:8]=2)[C:1]#[N:2])[N:10]=1

Participants

3

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-difluorobenzonitrileHCID 86762641HCID 86762641, compound

Product 1

HCID 762818485-[(4aR,6R,8aS)-2-amino-6-(methoxymethyl)-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile

Procedure

N-[(4aR,6R,8aS)-8a-(5-Cyano-2,4-difluorophenyl)-6-(methoxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C16) 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: 13.2 mg, 38.0 μmol, 19%. LCMS m/z 354.2 [M+H+]. 1H NMR (400 MHz, CD3OD), δ 7.64 (t, J=7.8 Hz, 1H), 7.3 (dd, J=12, 9.1 Hz, 1H), 4.01 (dd, J=11.1, 2.5 Hz, 1H), 3.76-3.82 (m, 1H), 3.66 (d, J=11.1 Hz, 1H), 3.45 (dd, J=10.3, 6.4 Hz, 1H), 3.39 (dd, J=10.3, 3.9 Hz, 1H), 3.36 (s, 3H), 2.84-2.92 (m, 2H), 2.67-2.71 (m, 1H), 1.70-1.80 (m, 1H), 1.50-1.55 (m, 1H).

Sources & evidence

ORD record
ord-21de2f7d2e1b455bb6a97eb08d2d9d8c
Source dataset
uspto-grants-2015_12
Patent number
US09198917B2

Reaction notes

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