4-Methoxybenzoic Acid → US9656988, Example 110

HRID 1050523Notes

Reaction equation

HRID 1050523 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[N:10]=[C:11]([Cl:17])[C:12]([C:15]#[N:16])=[N:13][CH:14]=2)[CH2:4]1.[C:18](O)(=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Cl:17][C:11]1[N:10]=[C:9]([N:5]2[CH2:6][CH2:7][CH2:8][C@@H:3]([NH:2][C:18](=[O:27])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH2:4]2)[CH:14]=[N:13][C:12]=1[C:15]#[N:16]

Participants

7

Reactant 4

HCID 74784-Methoxybenzoic AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 118114941(R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile hydrochloride

Product 1

HCID 118115072US9656988, Example 110

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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

  1. washwashed with 1N NaOH and water
  2. customThe organic phase was dried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-0640600209014a6b9212b4e26ba5a9d7
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…