1,2-Dichloroethane → HCID 67386628, compound

HRID 1898638Notes

Reaction equation

HRID 1898638 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH:13]=[C:12]([C:14]2[N:15]=[C:16]3[C:22]([C:23]([OH:25])=O)=[CH:21][N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:17]3=[N:18][CH:19]=2)[N:11]=[CH:10]1.[NH2:34][C@H:35]([CH:44]1[CH2:46][CH2:45]1)[C:36]([N:38]1[CH2:41][CH:40]([C:42]#[N:43])[CH2:39]1)=[O:37].C(Cl)CCl>CN(C1C=CN=CC=1)C.ClCCl>[C:42]([CH:40]1[CH2:41][N:38]([C:36](=[O:37])[C@H:35]([NH:34][C:23]([C:22]2[C:16]3[C:17](=[N:18][CH:19]=[C:14]([C:12]4[N:11]=[CH:10][N:9]([C:3]5[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=5[F:1])[CH:13]=4)[N:15]=3)[N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[CH:21]=2)=[O:25])[CH:44]2[CH2:45][CH2:46]2)[CH2:39]1)#[N:43]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 57516657HCID 57516657, compoundHCID 67386109HCID 67386109, compound

Product 1

HCID 67386628HCID 67386628, compoundYield 49.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.067 g, 0.14 mmol), (R)-1-(2-amino-2-cyclopropylacetyl)azetidine-3-carbonitrile (0.038 g, 0.21 mmol), DMAP (0.021 g, 0.17 mmol) and EDC (0.036 g, 0.19 mmol) in 2 mL dichloromethane was stirred for 13.5 h. Dichloromethane (10 mL) was added, and the solution was sequentially washed with 10 mL of a 1 M citric acid solution, 10 mL of water, and 10 mL of a sat. aq. NaCl solution then dried over Na2SO4, filtered and concentrated. The residue was purified using column chromatography (80% EtOAc/hexanes) to afford 0.044 g (48%) of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a foamy pale yellow solid. MS: (M+Na)+=655.

Workup

  1. washthe solution was sequentially washed with 10 mL of a 1 M citric acid solution, 10 mL of water, and 10 mL of a sat. aq. NaCl solution
  2. dry with materialthen dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-6776405c04854c85bdf5e0b1e9a67ea0
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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