Reaction equation
[CH2:1]([O:5][C:6]1[N:7]=[CH:8][C:9]([C:12]([OH:14])=O)=[N:10][CH:11]=1)[C:2]#[C:3][CH3:4].[CH3:15][C:16]1[C:17]([NH2:31])=[N:18][C:19]2([C:29]3[C:24](=[CH:25][CH:26]=[C:27]([NH2:30])[CH:28]=3)[O:23][CH2:22][CH2:21]2)[N:20]=1>>[NH2:31][C:17]1[C:16]([CH3:15])=[N:20][C:19]2([C:29]3[C:24](=[CH:25][CH:26]=[C:27]([NH:30][C:12]([C:9]4[CH:8]=[N:7][C:6]([O:5][CH2:1][C:2]#[C:3][CH3:4])=[CH:11][N:10]=4)=[O:14])[CH:28]=3)[O:23][CH2:22][CH2:21]2)[N:18]=1Participants
Procedure
The title compound (28 mg, 24% yield) was prepared as described for Example 13a starting from 5-(but-2-ynyloxy)pyrazine-2-carboxylic acid (Intermediate 36, 58 mg, 0.30 mmol) and 5′-methylspiro[chroman-4,2′-imidazole]-4′,6-diamine (Intermediate 30, 63 mg, 0.27 mmol). The crude product was purified by flash chromatography (4 g silica, gradient elution of (EtOAc/MeOH/conc. NH3 (80/20/1) in heptane) followed by preparative chromatography. The pure fractions were combined and evaporated. The residual oil was solidified by evaporation with EtOAc and heptanes: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.85 (t, 3 H), 1.88-1.96 (m, 2 H), 2.23 (s, 3 H), 4.28-4.48 (m, 2 H), 5.07 (q, 2 H), 6.55 (s, 2 H), 6.79 (d, 1 H), 7.02-7.10 (m, 1 H), 7.55-7.64 (m, 1 H), 8.39 (d, 1 H), 8.84 (d, 1 H), 10.26 (s, 1 H); MS (APCI+) m/z 405 [M+H]+.
Workup
- customThe crude product was purified by flash chromatography (
- wash4 g silica, gradient elution of (EtOAc/MeOH/conc. NH3 (80/20/1) in heptane)
- customevaporated
- customThe residual oil was solidified by evaporation with EtOAc and heptanes
Sources & evidence
- ORD record
- ord-d3b76fa700e941e2b0b19b23fd9c6cb5
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08865911B2
Linked notes
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