HCID 71278256, compound → HCID 71268737, compound

HRID 1427404Notes

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][CH:23]=[CH:22][C:21]=2[F:26])[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:19][CH2:18][C@@H:16]1[O:15][CH2:14][C@:12]2([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[N:13]=[C:8]([NH2:7])[S:9][CH2:10][C@@H:11]2[CH2:17]1

Participants

Reactant 2

HCID 71278256HCID 71278256, compound

HCID 131732348HCID 131732348, compound

Product 1

HCID 71268737HCID 71268737, compound

Procedure

tert-Butyl[(4aR,6R,8aS)-6-(fluoromethyl)-8a-(2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]carbamate (C26) 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: 25% to 100% B). Yield: 3 mg, 0.01 mmol, 10%. LCMS m/z 299.1 (M+1). 1H NMR (600 MHz, DMSO-d6) δ 1.43-1.48 (m, 1H), 1.63-1.72 (m, 1H), 2.64-2.72 (m, 2H), 2.75-2.80 (m, 1H), 3.60 (d, J=11.0 Hz, 1H), 3.76-3.85 (m, 1H), 3.96 (dd, J=10.8, 1.5 Hz, 1H), 4.30-4.48 (m, 2H), 6.13 (br s, 2H), 7.14-7.22 (m, 2H), 7.30-7.36 (m, 2H).

Workup

customIn this case, the reversed-phase HPLC purification

Sources & evidence

ORD record: ord-2d9649d8da5c4c48a9e7f17cc195b45d
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933221B2

Reaction notes

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