3-Ethoxy-6-methylpyridine-2-carboxylic acid → N-[((1S,4S,6S)-3-{[3-(Ethyloxy)-6-methyl-2-pyridinyl]carbonyl}-3-azabicyclo[4.1.0]hept-4-yl)methyl]-5-(trifluoromethyl)-2-pyridinamine
Reaction equation
[C@H:1]12[CH2:7][C@H:6]1[CH2:5][C@@H:4]([CH2:8][NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]=1)[NH:3][CH2:2]2.[CH2:20]([O:22][C:23]1[C:24]([C:30](O)=[O:31])=[N:25][C:26]([CH3:29])=[CH:27][CH:28]=1)[CH3:21]>>[CH2:20]([O:22][C:23]1[C:24]([C:30]([N:3]2[C@H:4]([CH2:8][NH:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:17])[F:18])=[CH:12][N:11]=3)[CH2:5][C@H:6]3[C@H:1]([CH2:7]3)[CH2:2]2)=[O:31])=[N:25][C:26]([CH3:29])=[CH:27][CH:28]=1)[CH3:21]Participants
Reactant 2
Product 1
Procedure
Following a similar procedure to that described for Example 1, N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyridinamine D12 (0.030 g) and 3-(ethyloxy)-6-methyl-2-pyridinecarboxylic acid D15 (0.020 g) were reacted to give the free base of the title compound (0.044 g, 0.101 mmol, 92% yield). HPLC (walk-up): rt=4.14 min. MS: m/z (ES/+): 435 (M+1). C22H25F3N4O2 requires 434. 1H NMR [the SYN relative stereochemistry is derived from the stereochemistry of the previous intermediate D8. The product is present as a mixture of conformers. The assignment is provided for the major component] (400 MHz, DMSO-d6) δ ppm: 8.26 (m, 1 H), 7.72-7.56 (m, 1 H), 7.18-7.47 (m, 3H), 6.83-6.61 (m, 1 H), 4.24-4.10 (m, 1 H), 4.10-3.88 (m, 2 H), 3.67-3.34 (m, 3 H), 2.67-2.56 (m, 1 H), 2.43-2.37 (s, 3 H), 2.43-2.34 (m, 1 H), 1.23-1.19 (m, 3 H), 1.20-0.8 (m, 3 H), 0.72-0.58 (m, 1 H), 0.15-0.24 (m, 1 H).
Workup
- customwere reacted
Sources & evidence
- ORD record
- ord-7ef9bd7124604db4b8ecb587840ded2c
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08133908B2
Reaction notes
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