Methanol → Ammonium Hydroxide
Reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@H:8]([OH:9])[CH2:7][CH2:6][N:5]([CH2:10][CH2:11][N:12]2[C:17](=[O:18])[CH:16]=[N:15][C:14]3[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[N:22][C:13]2=3)[CH2:4]1.CO.[O:27]1[C:36]2[CH:35]=[C:34]([CH:37]=O)[N:33]=[CH:32][C:31]=2[O:30][CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:54]>>[NH4+:1].[OH-:9].[ClH:54].[ClH:54].[O:27]1[C:36]2[CH:35]=[C:34]([CH2:37][NH:1][CH2:2][C@@H:3]3[C@H:8]([OH:9])[CH2:7][CH2:6][N:5]([CH2:10][CH2:11][N:12]4[C:17](=[O:18])[CH:16]=[N:15][C:14]5[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[N:22][C:13]4=5)[CH2:4]3)[N:33]=[CH:32][C:31]=2[O:30][CH2:29][CH2:28]1Participants
Procedure
To a mixture of [4-{2-[(3S,4R)-3-(aminomethyl)-4-hydroxy-1-piperidinyl]ethyl}-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one (for a preparation see Example 135(i); 0.157 g; 0.471 mmol) in anhydrous DCM (20 mL) and anhydrous MeOH (4 mL) was added 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (0.042 g; 0.471 mmol) and activated 4A sieves. The reaction was stirred under N2 for 18 h. The crude intermediate was treated with sodium triacetoxyborohydride (0.942 mmol; 199 mg) and stirred for 2 h. The product was obtained as a pale yellow oil after column:chromatography (90:10:0.5:DCM:MeOH:NH4OH) to yield 24 mg (11%) of the free base of the title compound. The bis-HCl salt was made by addition of 1N HCl/ether (0.098 mL) to yield the title compound as a light brown solid.
Workup
- stirringstirred for 2 h
- customThe product was obtained as a pale yellow oil after column
Sources & evidence
- ORD record
- ord-b08b5939edd945ee808bc68a3d0d0a79
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08071592B2
Reaction notes
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