3-(2-Trifluoroacetamidoethoxy)propyne → 5'-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2',3'-dideoxyuridine

HRID 76956Notes

Reaction equation

HRID 76956 reaction equation
[Si:1]([O:8][O:9][CH2:10][C@H:11]1[O:15][C@@H:14]([N:16]2[CH:23]=[C:22]([CH2:24]Br)[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:13][CH2:12]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:26][C:27]([F:38])([F:37])[C:28]([NH:30][CH2:31][CH2:32][O:33][CH2:34][C:35]#[CH:36])=[O:29]>>[Si:1]([O:8][O:9][CH2:10][C@H:11]1[O:15][C@@H:14]([N:16]2[CH:23]=[C:22]([CH2:24][C:36]#[C:35][CH2:34][O:33][CH2:32][CH2:31][NH:30][C:28](=[O:29])[C:27]([F:26])([F:37])[F:38])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:13][CH2:12]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 167426213-(2-Trifluoroacetamidoethoxy)propyneHCID 873646485'-O-tert-butyldimethylsilyloxy-5-bromomethyl-2',3'-dideoxyuridine

Product 1

HCID 873650905'-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2',3'-dideoxyuridine

Procedure

Next, 5′-O-tert-butyldimethylsilyloxy-5-bromomethyl-2′,3′-dideoxyuridine (3) can be coupled with an alkyne, in this case 3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne, to form the 5′-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2′,3′-dideoxyuridine (4). It will be readily appreciated by one of skill in the art that the coupling of an alkyl halide with an alkyne can be carried out by a number of methods known in the art. Without being limiting in any way, one example of such a method known in the art is the so-called Castro-Stephens coupling, see for example, White, J. D., et. al. J. Am. Chem. Soc., 123(23), 5407-5413 (2001) and Stephens, R. D., et. al. J. Org. Chem., 28, 3313 (1963). For example, as shown in Scheme 1,5′-O-tert-butyldimethylsilyloxy-5-bromomethyl-2′,3′ dideoxyuridine (3) can be contacted with a mixture comprising a copper reagent, for example copper iodide (CuI), an alkyne, for example 3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne, and a base, for example 1,8-diazobicyloclo[5.4.0]undec-7-ene (DBU), to form 5′-O-tert-butyldimethylsilyloxy-(5-(4-(N-trifluoroacetyl-2-aminoethoxy)but-2-yn-1-yl))-2′,3′-dideoxyuridine (4), where an acetylide anion is formed in the mixture comprising CuI, 3-(N-trifluoroacetyl-2-aminoethoxy)prop-1-yne, and DBU.

Sources & evidence

ORD record
ord-e147054dc4c04bb7be2e33b1b9d6e0c2
Source dataset
uspto-grants-2014_09
Patent number
US08835625B2

Reaction notes

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