4H-Cyclopenta-1,3-dioxol-4-ol, 5-fluoro-3a,6a-dihydro-2,2-dimethyl-6-[(triphenylmethoxy)methyl]-, 4-methanesulfonate, (3aR,4R,6aR)- → 4-Amino-1-[(1S,4R,5S)-2-fluoro-4,5-dihydroxy-3-(hydroxymethyl)-2-cyclopenten-1-yl]-2(1H)-pyrimidinone
Reaction equation
CS([O:5][C@@H:6]1[C@H:13]2[C@H:9]([O:10][C:11]([CH3:15])([CH3:14])[O:12]2)[C:8]([CH2:16][O:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:7]1[F:37])(=O)=O.[NH:38]1[CH:45]=[CH:44][C:42]([NH2:43])=[N:41][C:39]1=[O:40]>>[CH2-:7][C:6]([CH3:13])=[O:5].[NH2:43][C:42]1[CH:44]=[CH:45][N:38]([C@H:6]2[C@H:13]([OH:12])[C@H:9]([OH:10])[C:8]([CH2:16][OH:17])=[C:7]2[F:37])[C:39](=[O:40])[N:41]=1.[F:37][C:7]1[C@H:6]([OH:5])[C@@H:13]2[O:12][C:11]([CH3:15])([CH3:14])[O:10][C@@H:9]2[C:8]=1[CH2:16][O:17][C:18]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1Participants
5
Reactant 2
Product 3
Procedure
A reaction using the mesylate 11 and displacement with cytosine under KOtBu/DMSO conditions gave complete conversion, approximately 90% in favour of the desired N1-alkylated product, with the remainder being the O-alkylated product. The two were readily separated by chromatography. After subsequent trityl and acetonide deprotection, compound 13 was afforded with chemical purity of 98.34% area in 50% yield from alcohol 10.
Workup
- customgave complete conversion, approximately 90% in favour of the desired N1-alkylated product
- customThe two were readily separated by chromatography
Sources & evidence
- ORD record
- ord-2afca9e78de047f1889ad7feb4607e3d
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09150520B2
Reaction notes
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