1,4-Anhydrothreitol → 3'-fluoro-4'-({5-oxo-7-propyl-4-[(3a'R,6a'S)-tetrahydrospiro[cyclohexane-1,2'-furo[3,4-d][1,3]dioxol]-4-yl]-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile

HRID 519624Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:29]2[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:28])[N:11]([CH:21]2[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]2)[C:12]2[N:13]([N:18]=[CH:19][N:20]=2)[C:14]=1[CH2:15][CH2:16][CH3:17].[O:37]1[CH2:41][CH:40](O)[CH:39]([OH:43])[CH2:38]1>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:29]2[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:28])[N:11]([CH:21]2[CH2:22][CH2:23][C:24]3([O:43][C@H:39]4[CH2:38][O:37][CH2:41][C@H:40]4[O:27]3)[CH2:25][CH2:26]2)[C:12]2[N:13]([N:18]=[CH:19][N:20]=2)[C:14]=1[CH2:15][CH2:16][CH3:17]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 3′-fluoro-4′-{[5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (1 g), tetrahydrofuran-3,4-diol (0.26 g), p-toluenesulfonic acid monohydrate (0.005 g) and toluene (50 mL) was subjected to an azeotropic dehydration reaction by stirring at 110° C. for 3 hr in a reaction vessel equipped with a Dean-stark trap. The reaction mixture was concentrated, and the obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.3 g, 100%).

Workup

customwas subjected to an azeotropic dehydration reaction
customequipped with a Dean-stark trap
concentrationThe reaction mixture was concentrated
customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-e878a21451c04b49ba0c0973c3da9c49
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115136B2

Reaction notes

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