Hydrochloric Acid → (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile hydrochloride
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14]C(=O)OC(C)(C)C)[CH2:9]2)[CH:5]=[N:4][C:3]=1[C:22]#[N:23].Cl>O1CCOCC1>[ClH:1].[NH2:14][C@@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]2[N:7]=[C:2]([Cl:1])[C:3]([C:22]#[N:23])=[N:4][CH:5]=2)[CH2:9]1Participants
Procedure
(R)-tert-butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate (87) (1.5 g) was treated with 30 mL “4N HCl in dioxane” at RT for 1 h. The mixture was concentrated in vacuo to dryness to afford (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile hydrochloride (134) in quantitative yield. Compound 134 (1.20 g, 4.4 mmol) and p-anisic acid (1.34 g, 8.8 mmol) were dissolved in 20 mL DMF with DIEA (3.82 mL, 22.0 mmol). To it was added PyBOP (4.58 g, 8.8 mmol). The mixture was stirred at RT for 30 m. It was diluted with EtOAc (200 mL), washed with 1N NaOH and water. The organic phase was dried, concentrated and subjected to flash column with 0 to 50% EtOAc in DCM to isolate (R)—N-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-4-methoxybenzamide, compound 135 (yield >90%).
Workup
- concentrationThe mixture was concentrated in vacuo to dryness
Sources & evidence
- ORD record
- ord-45265510e62a4b5dbcef0c8a0fea6f75
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382246B2
Reaction notes
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