HCID 71278246, compound → HCID 71268741, compound

HRID 1427402Notes

Reaction equation

C(OC(=O)[NH:7][C:8]1[S:9][CH2:10][C@@H:11]2[CH2:17][C@H:16]([CH2:18][F:19])[O:15][CH2:14][C@:12]2([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[N:13]=1)(C)(C)C.FC(F)(F)C(O)=O.FC1C=CC=CC=1[C@]12CO[C@@H](COC(C)C)C[C@H]1CSC(N)=N2>>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C@:12]12[CH2:14][O:15][C@@H:16]([CH2:18][F:19])[CH2:17][C@H:11]1[CH2:10][S:9][C:8]([NH2:7])=[N:13]2

Participants

Reactant 2

HCID 71278246HCID 71278246, compound

HCID 131732348HCID 131732348, compound

Product 1

HCID 71268741HCID 71268741, compound

Procedure

tert-Butyl[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]carbamate (C25) was converted to the product according to the general procedure for the synthesis of (4aR,6R,8aS)-8a-(2-fluorophenyl)-6-[(propan-2-yloxy)methyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine, trifluoroacetate salt (2) in Example 2. In this case, the reversed-phase HPLC purification was carried out using a different system (Column: Waters XBridge C18, 5 μm; Mobile phase A: 0.03% ammonium hydroxide in water (v/v); Mobile phase B: 0.03% ammonium hydroxide in acetonitrile (v/v); Gradient: 5% to 100% B), affording the product as an oil. Yield: 17 mg, 0.054 mmol, quantitative. LCMS m/z 317.2 (M+1). 1H NMR (600 MHz, DMSO-d6) δ 1.56-1.64 (m, 1H), 1.66-1.72 (m, 1H), 2.88 (dd, J=13.2, 3.5 Hz, 1H), 3.02 (br d, J=13 Hz, 1H), 3.14-3.21 (m, 1H), 3.88 (d, half of AB quartet, J=12.3 Hz, 1H), 3.92-4.01 (m, 2H), 4.38-4.57 (m, 2H), 7.21-7.26 (m, 1H), 7.28-7.34 (m, 1H), 7.36-7.41 (m, 1H).

Workup

customIn this case, the reversed-phase HPLC purification

Sources & evidence

ORD record: ord-7ba47b5eec9d4fb5b3ad9508d3caa957
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933221B2

Reaction notes

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