Dichloromethane → Hydrochloric Acid
Reaction equation
[C:1]([C:4]1[N:5]=[CH:6][C:7]([N:28]2[CH2:33][CH2:32][CH2:31][C@@H:30]([NH:34]C(=O)OC(C)(C)C)[C@H:29]2[CH3:42])=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O.C(Cl)[Cl:51]>>[NH2:34][C@@H:30]1[CH2:31][CH2:32][CH2:33][N:28]([C:7]2[N:8]=[C:9]([NH:10][C:11]3[CH:12]=[CH:13][C:14]([CH:17]4[CH2:22][CH2:21][N:20]([CH:23]5[CH2:24][CH2:25][CH2:26][CH2:27]5)[CH2:19][CH2:18]4)=[CH:15][CH:16]=3)[C:4]([C:1]([NH2:2])=[O:3])=[N:5][CH:6]=2)[C@@H:29]1[CH3:42].[ClH:51]Participants
Reactant 3
Product 2
Procedure
tert-Butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (313) (430 mg, 0.74 mmol) was treated in DCM (20 mL) and TFA (7 mL) at room temperature for 2 hours. The mixture was concentrated in vacuo, dissolved in MeOH/water, and subjected to reverse phase prep HPLC using 5 mM HCl in water and neat MeCN as mobile phases to isolate 5-((2R,3R)-3-amino-2-methylpiperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (314) as HCl salt. LC-MS (ESI): m/z (M+1) 478.5. UV: λ=264, 274, 304, 335, 372 nm. Proton NMR (CD3OD): δ 7.66 (1H, s), 7.58 (2H, d, J=8.5 Hz), 7.27 (2H, d, J=8.5 Hz), 5.03 (1H, m), 4.32 (1H, d, J=11.0 Hz), 3.72 (2H, d, J=10.0 Hz), 3.56 (1H, m), 3.45 (1H, m), 3.14 (2H, m), 3.11 (1H, m), 2.88 (1H, m), 2.22-1.70 (16H, m), 1.32 (3H, d, J=7.0 Hz) ppm.
Workup
- concentrationThe mixture was concentrated in vacuo
- dissolutiondissolved in MeOH/water
Sources & evidence
- ORD record
- ord-d53f4fa5ada14d5aaffac1239ddb2fca
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382246B2
Reaction notes
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