1H-Imidazole-1-propanamine → {[(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 2-{[3-(1H-imidazol-1-yl)propyl]amino}-2-oxoethyl carbonate

HRID 1472728Notes

Reaction equation

HRID 1472728 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]([C:13]1[C:14](=[O:38])[C:15]([O:28][CH2:29][O:30][C:31]([O:33][CH2:34][C:35](O)=[O:36])=[O:32])=[C:16]2[C:21](=[O:22])[N:20]3[C@@H:23]([CH3:26])[CH2:24][O:25][C@@H:19]3[CH2:18][N:17]2[CH:27]=1)=[O:12].[N:39]1([CH2:44][CH2:45][CH2:46][NH2:47])[CH:43]=[CH:42][N:41]=[CH:40]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[C:31](=[O:32])([O:33][CH2:34][C:35]([NH:47][CH2:46][CH2:45][CH2:44][N:39]1[CH:43]=[CH:42][N:41]=[CH:40]1)=[O:36])[O:30][CH2:29][O:28][C:15]1[C:14](=[O:38])[C:13]([C:11]([NH:10][CH2:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[O:12])=[CH:27][N:17]2[C:16]=1[C:21](=[O:22])[N:20]1[C@@H:23]([CH3:26])[CH2:24][O:25][C@@H:19]1[CH2:18]2

Participants

5

Reactant 4

HCID 787361H-Imidazole-1-propanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44626082({[({[(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)oxy]carbonyl}oxy)acetic acid

Product 1

HCID 44626215{[(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 2-{[3-(1H-imidazol-1-yl)propyl]amino}-2-oxoethyl carbonate

Procedure

The title compound was prepared from ({[({[(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)oxy]carbonyl}oxy)acetic acid (63 mg, 0.112 mmol), [3-(1H-imidazol-1-yl)propyl]amine (0.02 mL, 0.176 mmol), N,N-diisopropylethylamine (0.03 mL, 0.176 mmol), and HATU (67 mg, 0.176 mmol), using a process similar to that described in example 16, step (a). Purification by silica gel chromatography yielded the title compound as a white solid. 1H NMR (CDCl3) δ 10.04 (m, 1 H), 8.16 (s, 1 H), 7.54 (m, 1 H), 7.47 (s, 1 H), 7.30 (m, 1 H), 6.94 (s, 1 H), 6.87 (s, 1 H), 6.77 (m, 2 H), 6.00 (d, J=6.8 Hz, 1 H), 5.65 (d, J=6.8 Hz, 1 H), 5.31-5.25 (m, 2 H), 4.62-4.41 (m, 4 H), 4.31 (m, 1 H), 4.19 (m, 1 H), 4.01-3.29 (m, 3 H), 3.02 (m, 1 H), 3.36 (m, 1 H), 3.03 (m, 1 H), 1.97 (m, 2 H), 1.28 (d, J=6.4 Hz, 3 H). ES+ MS: 645 (M+1).

Workup

  1. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-ad2531b37d794e718a304218d1e1bebf
Source dataset
uspto-grants-2015_04
Patent number
US09012650B2

Reaction notes

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