Diisopropylethylamine → (3aR,7aR)-tert-butyl 4-(6-chloro-5-cyanopyrazin-2-yl)octahydro-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

HRID 1050591Notes

Reaction equation

HRID 1050591 reaction equation
[N:1]1([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:9]2[C@H:4]([NH:5][CH2:6][CH2:7][CH2:8]2)[CH2:3][CH2:2]1.[Cl:17][C:18]1[C:19]([C:25]#[N:26])=[N:20][CH:21]=[C:22](Cl)[N:23]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:17][C:18]1[N:23]=[C:22]([N:5]2[CH2:6][CH2:7][CH2:8][C@H:9]3[N:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:2][CH2:3][C@@H:4]23)[CH:21]=[N:20][C:19]=1[C:25]#[N:26]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 529877443,5-Dichloropyrazine-2-carbonitrileHCID 713060651H-Pyrrolo[3,2-b]pyridine-1-carboxylic acid, octahydro-, 1,1-dimethylethyl ester, (3aR,7aR)-rel-

Product 1

HCID 118114837(3aR,7aR)-tert-butyl 4-(6-chloro-5-cyanopyrazin-2-yl)octahydro-1H-pyrrolo[3,2-b]pyridine-1-carboxylateYield 96.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Commercial (3aR,7aR)-tert-butyl octahydro-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (416, CAS: 1251010-63-5, 476 mg, 2.1 mmol) was dissolved in 15 mL DMF. To it were added 3,5-dichloropyrazine-2-carbonitrile (340 mg, 1.9 mmol) and DIEA (500 μL, 2.9 mmol). The mixture was stirred at RT for 3.5 hours, diluted with 100 mL EtOAc, washed with water ×3, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 3% MeOH in DCM to isolate (3aR,7aR)-tert-butyl 4-(6-chloro-5-cyanopyrazin-2-yl)octahydro-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (417, 670 mg, 88%) as a white solid.

Workup

  1. washwashed with water ×3
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b31f1910ec9d4b2eaba1e33d09e2f1bd
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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