Diisopropylethylamine → HCID 86685607, compound

HRID 332815Notes

Reaction equation

HRID 332815 reaction equation
[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](Cl)[N:7]=1.Cl.[NH2:12][C@@H:13]([C:17]([NH2:19])=[O:18])[CH:14]([CH3:16])[CH3:15].CCN(C(C)C)C(C)C>C(C#N)(C)=O.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:12][C@H:13]([CH:14]([CH3:16])[CH3:15])[C:17]([NH2:19])=[O:18])[CH:5]=[N:4][C:3]=1[C:9]#[N:10]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 529877443,5-Dichloropyrazine-2-carbonitrileHCID 53486046(2R)-2-amino-3-methylbutanamide hydrochloride

Product 1

HCID 86685607HCID 86685607, compoundYield 102.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 694302-OxopropiononitrileSolvent

Procedure

To a mixture of 3,5-dichloropyrazine-2-carbonitrile (500 mg, 2.84 mmol) and D-valinamide HCl salt (476 mg, 3.12 mmol) in AcCN (10 mL) was added DIPEA (1.11 mL, 6.25 mmol). After stirring at room temperature for 4 h, it was diluted with EtOAc, washed with sat. NaHCO3, organic layer was separated and washed with brine, dried and concentrated to give (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-methylbutanamide (740 mg). Step 2: To a mixture of (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-methylbutanamide (100 mg, 0.394 mmol) in Dioxane (2 mL) was added 3-aminoquinoline (71 mg, 0.492 mmol), Pd(OAc)2 (18 mg, 0.079 mmol), BINAP (49 mg, 0.079 mmol) and K2CO3 (163 mg, 1.18 mmol). After heating at 95° C. for 5 h, the mixture was filtered, the filtrate was concentrated and purified by preparative HPLC to give (R)-2-(5-cyano-6-(quinolin-3-yl)pyrazin-2-ylamino)-3-methylbutanamide (113 mg).

Workup

  1. washwashed with sat. NaHCO3, organic layer
  2. customwas separated
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-cc9f3d46b950432e9ddd01c843baf456
Source dataset
uspto-grants-2014_11
Patent number
US08877760B2

Reaction notes

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