Potassium Carbonate → {[(3S,11aR)-8-({[(2,4-Difluorophenyl)methyl]amino)carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1.3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 3-hydroxypropyl carbonate

HRID 1618364Notes

Reaction equation

HRID 1618364 reaction equation
[C:1](=[O:45])([O:33][CH2:34][CH2:35][CH2:36][O:37]CC1C=CC=CC=1)[O:2][CH2:3][O:4][C:5]1[C:6](=[O:32])[C:7]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[F:31])=[O:21])=[CH:8][N:9]2[C:14]=1[C:13](=[O:15])[N:12]1[C@@H:16]([CH3:19])[CH2:17][O:18][C@@H:11]1[CH2:10]2.[Na].FC1C=C(F)C=CC=1CNC(C1C(=O)C(O)=C2C(=O)N3[C@@H](C)CO[C@@H]3CN2C=1)=O.C(=O)(OCCCOCC1C=CC=CC=1)OCI.C(=O)([O-])[O-].[K+].[K+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:1](=[O:45])([O:33][CH2:34][CH2:35][CH2:36][OH:37])[O:2][CH2:3][O:4][C:5]1[C:6](=[O:32])[C:7]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[F:31])=[O:21])=[CH:8][N:9]2[C:14]=1[C:13](=[O:15])[N:12]1[C@@H:16]([CH3:19])[CH2:17][O:18][C@@H:11]1[CH2:10]2

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11759878[3-(Benzyloxy)propyl] iodomethyl carbonateHCID 66594573GSK1265744 (sodiuM salt)HCID 67300296{[(3S,11aR)-8-({[(2,4-Difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 3-[(phenylmethyl)oxy]propyl carbonate

Product 1

HCID 44626015{[(3S,11aR)-8-({[(2,4-Difluorophenyl)methyl]amino)carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1.3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 3-hydroxypropyl carbonateYield 95%

Reagents, catalysts & solvents 1

HCID 94433Tetrabutylammonium hydrogen sulfateCatalyst

Procedure

{[(3S,11aR)-8-({[(2,4-Difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 3-[(phenylmethyl)oxy]propyl carbonate. The title compound was prepared in 95% yield according to example 1 from 1b (1.00 g, 2.34 mmol), iodomethyl 3-[(phenylmethyl)oxy]propyl carbonate (3.24 g, 9.25 mmol), potassium carbonate (1.97 g, 14.3 mmol) and tetrabutylammonium hydrogen sulfate (1.30 g, 3.83 mmol). 1H NMR (400 MHz, CDCl3) δ ppm 10.18 (t, J=5.7 Hz, 1H), 8.37 (s, 1H), 7.35-7.20 (m, 6H), 6.83-6.72 (m, 2H), 5.92 (d, J=6.6 Hz, 1H), 5.83 (d, J=6.6 Hz, 1H), 5.25 (dd, J=9.9, 3.8 Hz, 1H), 4.65-4.50 (m, 2H), 4.46 (s, 2H), 4.37-4.22 (m, 5H), 3.86 (dd, J=12.2, 10.0 Hz, 1H), 3.62 (dd, J=8.5, 6.9 Hz, 1H), 3.55 (t, J=6.2 Hz, 2H), 2.04-1.92 (m, 2H), 1.34 (d, J=6.2 Hz, 3H); ES+ MS: 628 (M+1).

Sources & evidence

ORD record
ord-c24af51f608341ab9ac638efe567c52b
Source dataset
uspto-grants-2014_07
Patent number
US08765965B2

Reaction notes

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