1,2-Dichloroethane → HCID 67386346, compound

HRID 1898495Notes

Reaction equation

HRID 1898495 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.Cl.[NH2:25][C@H:26]([C:34]([CH3:37])([CH3:36])[CH3:35])[C:27]([N:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:25][C@H:26]([C:34]([CH3:37])([CH3:36])[CH3:35])[C:27](=[O:28])[N:29]4[CH2:30][CH2:31][CH2:32][CH2:33]4)=[O:15])=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:21])([CH3:22])[CH3:23])[C:7]3=[N:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57516598(R)-2-amino-3,3-dimethyl-1-(pyrrolidin-1-yl)butan-1-one hydrochlorideHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 67386346HCID 67386346, compoundYield 108.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 10 mL round-bottomed flask was charged with 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.12 g, 0.36 mmol), (R)-2-amino-3,3-dimethyl-1-(pyrrolidin-1-yl)butan-1-one hydrochloride (137 mg, 0.53 mmol), HOBt (61 mg, 0.40 mmol) and EDC (76 mg, 0.40 mmol). Then added DMF (1.6 mL) followed by N,N-diisopropylethylamine (0.16 mL, 0.92 mmol). The light yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with diethyl ether (2×50 mL). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over 8 g SiO2 with EtOAc/hexanes (gradient: 0-60% EtOAc) to afford 195 mg of (R)-2-cyclopropyl-N-(3,3-dimethyl-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide as a viscous yellow oil.

Workup

  1. customthen quenched with water
  2. extractionextracted with diethyl ether (2×50 mL)
  3. washThe combined organic layers were washed twice with water and once with brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography over 8 g SiO2 with EtOAc/hexanes (gradient: 0-60% EtOAc)

Sources & evidence

ORD record
ord-461c424353c1403198129b8102b14f49
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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