1,2-Dichloroethane → HCID 67002193, compound

HRID 2191559Notes

Reaction equation

HRID 2191559 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.Cl.[NH2:25][C:26]1([C:31]([OH:34])([CH3:33])[CH3:32])[CH2:30][CH2:29][CH2:28][CH2:27]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[OH:34][C:31]([C:26]1([NH:25][C:13]([C:12]2[C:6]3[C:7](=[N:8][CH:9]=[C:4]([CH:1]4[CH2:2][CH2:3]4)[N:5]=3)[N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:21])[CH3:23])[CH:11]=2)=[O:14])[CH2:30][CH2:29][CH2:28][CH2:27]1)([CH3:33])[CH3:32]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 67001422HCID 67001422, compound

Product 1

HCID 67002193HCID 67002193, compoundYield 101.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a round-bottomed flask were combined 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 0.45 mmol), 2-(1-amino-cyclopentyl)-propan-2-ol hydrochloride (115 mg, 0.64 mmol), EDC (95 mg, 0.50 mmol), and HOBt (67 mg, 0.50 mmol). Then added DMF (2 mL) followed by i-Pr2NEt (0.20 mL, 1.12 mmol). The reaction mixture was stirred at room temperature overnight then quenched with H2O and extracted with EtOAc (3×). The combined organics were washed with H2O (3×) and brine then dried over Na2SO4 and concentrated. The residue was purified by chromatography over 12 g of SiO2 using EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 209 mg (96%) of 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-hydroxy-1-methyl-ethyl)-cyclopentyl]-amide as a pale yellow oil.

Workup

  1. customIn a round-bottomed flask were combined
  2. customthen quenched with H2O
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organics were washed with H2O (3×) and brine
  5. dry with materialthen dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography over 12 g of SiO2

Sources & evidence

ORD record
ord-bcc1687fa56f4bb5a1925b384967d341
Source dataset
uspto-grants-2012_12
Patent number
US08329699B2

Reaction notes

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