Gemcitabine → 4-amino-1-((6aR,8R,9aR)-9,9-difluoro-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)pyrimidin-2(1H)-one

HRID 64246

Reaction equation

HRID 64246 reaction equation
[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=[O:5])[N:3]([C@@H:9]2[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C:10]2([F:18])[F:17])[CH:2]=1.Cl[Si:20]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[O:21][Si:22](Cl)([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24]>N1C=CC=CC=1>[NH2:8][C:7]1[CH:1]=[CH:2][N:3]([C@@H:9]2[O:13][C@H:12]3[C@@H:11]([O:16][Si:20]([CH:30]([CH3:32])[CH3:31])([CH:33]([CH3:35])[CH3:34])[O:21][Si:22]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:24])[CH3:25])[O:15][CH2:14]3)[C:10]2([F:17])[F:18])[C:4](=[O:5])[N:6]=1

Participants

4

Reactant 2

HCID 60750GemcitabineHCID 1724041,3-Dichlorotetraisopropyldisiloxane

Product 1

HCID 901365764-amino-1-((6aR,8R,9aR)-9,9-difluoro-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)pyrimidin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

As shown above, Gemcitabine (4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one) can be treated with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (TIPDSiCl2) in dry pyridine to provide 4-amino-1-((6aR,8R,9aR)-9,9-difluoro-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)pyrimidin-2(1H)-one. It is contemplated that other 1,3-dihalo-1,1,3,3-tetraalkyldisiloxanes can be used in place of TIPDSiCl2. It is also contemplated that two monofunctional halosiloxane protecting groups can be used in place of the difunctional TIPDSiCl2. Further, it is also contemplated that other hydroxyl protecting groups (e.g., tetrahydropyranyl (THP) or acetyl (Ac)) can be used in place of TIPDSiCl2.

Sources & evidence

ORD record
ord-391119ebd8214ccba3a41b7a857c9475
Source dataset
uspto-grants-2016_09
Patent number
US09447137B2

Linked notes

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