HCID 90253541, compound → HCID 90253554, compound

HRID 1478779Notes

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]([C@@H:19]3[CH2:23][CH2:22][CH2:21][O:20]3)[CH2:15][C@H:14]1[CH2:13][S:12][C:11]([NH:24]C(=O)C1C=CC=CC=1)=[N:10]2.Cl.C1([C@@H]2OC[C@]3(C4C=CC(F)=CC=4F)N=C(N)S[C@H](CF)[C@@H]3C2)CC1>>[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]([C@@H:19]3[CH2:23][CH2:22][CH2:21][O:20]3)[CH2:15][C@H:14]1[CH2:13][S:12][C:11]([NH2:24])=[N:10]2

Participants

Reactant 2

HCID 90253541HCID 90253541, compound

HCID 131736525HCID 131736525, compound

Product 1

HCID 90253554HCID 90253554, compound

Procedure

N-{(4aR,6R,8aS)-8a-(2,4-Difluorophenyl)-6-[(2S)-tetrahydrofuran-2-yl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl}benzamide (C103) was converted to the product using the method described for the synthesis of (4S,4aR,6R,8aS)-6-cyclopropyl-8a-(2,4-difluorophenyl)-4-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine, hydrochloride salt (6) in Example 6. Purification by reversed phase HPLC {Column: Phenomenex Gemini C18, 8 μm; Gradient: 36% to 56% acetonitrile in water [ammonia (pH 10)]} provided the product as a white solid. Yield: 193 mg, 0.545 mmol, 25%. LCMS m/z 355.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.31-7.37 (m, 1H), 6.75-6.87 (m, 2H), 4.06 (dd, J=11, 2.0 Hz, 1H), 3.73-3.90 (m, 4H), 3.51 (ddd, J=10.8, 6.5, 2.3 Hz, 1H), 2.95 (dd, J=12.0, 4.0 Hz, 1H), 2.83-2.89 (m, 1H), 2.60 (dd, J=12.3, 2.3 Hz, 1H), 1.97-2.05 (m, 1H), 1.73-1.94 (m, 4H), 1.64-1.69 (m, 1H).

Workup

customPurification by reversed phase HPLC {Column

Sources & evidence

ORD record: ord-80c6203749e9475dafaa1d75ff8a57c7
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403846B2

Reaction notes

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