Propargyl alcohol → N-(4-Fluoro-2-(3-hydroxyprop-1-ynyl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 348207Notes

Reaction equation

HRID 348207 reaction equation
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4](I)[CH:3]=1.[CH2:34]([OH:37])[C:35]#[CH:36]>>[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4]([C:36]#[C:35][CH2:34][OH:37])[CH:3]=1

Participants

3

Reactant 2

HCID 7859Propargyl alcoholHCID 21070019N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

Product 1

HCID 21070008N-(4-Fluoro-2-(3-hydroxyprop-1-ynyl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamideYield 85%

Procedure

Reaction of intermediate 174, N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.563 g, 1.00 mmol) with propargyl alcohol (0.18 ml, 3.2 mmol) using the conditions described for intermediate 178 gave 0.415 g (85% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.64 (6H, s, 2×CH3), 4.04 (4H, m, 2×CH2), 4.39 (2H, d, J=6.6 Hz, CH2), 4.68 (2H, d, J=6.0 Hz, CH2), 5.29 (2H, s, OCH2), 6.99 (1H, m, aromatic), 7.13 (1H, dd, J=2.5 Hz and J=9.1 Hz, aromatic), 7.22 (1H, dd, J=5.6 Hz and J=8.6 Hz, aromatic), 7.33–7.37 (3H, m, aromatics), 7.44–7.47 (2H, m, aromatics), 7.68 (1H, broad t, NH). HRMS (ESI+) calculated for C27H27FN3O5 [M+H+]: 492.1935. Found: 492.1939.

Sources & evidence

ORD record
ord-2eca3d215ab74118928adfcb4a93c6ec
Source dataset
uspto-grants-2007_02
Patent number
US07176196B2

Reaction notes

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