Ethanol → 3-{(3r,4r)-4-Methyl-3-[methyl(1h-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile

HRID 1529182Notes

Reaction equation

HRID 1529182 reaction equation
[CH3:1][N:2]([C@@H:12]1[C@H:17]([CH3:18])[CH2:16][CH2:15][NH:14][CH2:13]1)[C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[NH:9][CH:10]=[CH:11][C:4]=12.O=C1CCC(=O)N1[O:26][C:27](=O)[CH2:28][C:29]#[N:30].C(O)C>>[CH3:18][C@@H:17]1[CH2:16][CH2:15][N:14]([C:27](=[O:26])[CH2:28][C:29]#[N:30])[CH2:13][C@@H:12]1[N:2]([CH3:1])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[NH:9][CH:10]=[CH:11][C:4]=12

Participants

4

Reactant 3

HCID 702EthanolHCID 534158962,5-Dioxopyrrolidin-1-yl 2-cyanoacetateHCID 66662875N-methyl-N-[(3R,4R)-4-methylpiperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine

Product 1

HCID 115224753-{(3r,4r)-4-Methyl-3-[methyl(1h-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrileYield 182.5%

Procedure

A mixture of N-methyl-N-[(3R,4R)-4-methylpiperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine (43.0 mg, 0.000176 mol) and 3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropanenitrile (38 mg, 0.00021 mol) in ethanol (1 mL, 0.02 mol) was stirred overnight. The reaction mixture was partitioned between ethyl acetate/THF and sat. NaHCO3, and the organic layer was washed by sat. NaCl. The solvent was removed under vacuum to give 100 mg of an orange solid which was chromatographed with 7% MeOH/DCM, 0.7% NH4OH to give 17 mg of pale orange solid. The crude product was triturated with Et2O and the resulting solid was filtered and washed to give 9.4 mg of wet pale orange solid which was dried at from room temperature to about 60° C. for 3.5 h to give 6.5 mg of the final product.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate/THF and sat. NaHCO3
  2. washthe organic layer was washed by sat. NaCl
  3. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-904e8845cee24374aedecea1a08c270b
Source dataset
uspto-grants-2015_07
Patent number
US09090611B2

Reaction notes

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