1,2-Dichloroethane → HCID 67386679, compound

HRID 1898531Notes

Reaction equation

HRID 1898531 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13](O)=[O:14])=[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.[NH2:24][C@H:25]([C:41]([CH3:44])([CH3:43])[CH3:42])[C:26]([N:28]1[CH2:33][CH2:32][C:31]([OH:40])([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:30][CH2:29]1)=[O:27].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[OH:40][C:31]1([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:30][CH2:29][N:28]([C:26]([C@H:25]([NH:24][C:13]([C:12]2[C:6]3[C:7](=[N:8][CH:9]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[N:5]=3)[N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]=2)=[O:14])[C:41]([CH3:44])([CH3:43])[CH3:42])=[O:27])[CH2:33][CH2:32]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57516615HCID 57516615, compoundHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 67386679HCID 67386679, compoundYield 96.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 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-1-(4-hydroxy-4-phenylpiperidin-1-yl)-3,3-dimethylbutan-1-one (191 mg, 0.49 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 (0.12 mL, 0.68 mmol). The reaction mixture was stirred at room temperature over the weekend the quenched with water and extracted with diethyl ether (2×). The organic layers were combined and washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over 12 g SiO2 with 0-60% EtOAc/heptane to afford 0.21 g (94%) of 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-hydroxy-4-phenyl-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide as a light yellow oil.

Workup

  1. customquenched with water
  2. extractionextracted with diethyl ether (2×)
  3. washwashed 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 12 g SiO2 with 0-60% EtOAc/heptane

Sources & evidence

ORD record
ord-55a04c81674a4b9fa0ad5e3fff9d84cd
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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