1,2-Dichloroethane → HCID 178481748, compound

HRID 246138Notes

Reaction equation

HRID 246138 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[NH2:45][C@H:46]1[CH2:51][CH2:50][C@H:49]([OH:52])[CH2:48][CH2:47]1>ClCCl>[OH:52][C@H:49]1[CH2:50][CH2:51][C@H:46]([NH:45][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:30])[CH3:31])[CH:19]=2)=[O:23])[CH2:47][CH2:48]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 178511715HCID 178511715, compound

Product 1

HCID 178481748HCID 178481748, compoundYield 36.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In a 100 mL round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.150 g, 0.295 mmol), EDC (61 mg, 0.32 mmol), DIEA (52 μl, 0.295 mmol) were combined with dichloromethane (3 ml) to give a yellow solution. Stirred for 30 min then trans-4-aminocyclohexanol (48 mg, 0.42 mmol) was added. The reaction mixture was stirred at room temperature for 24 h then diluted with dichloromethane and washed with water. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 5% MeOH in DCM) and recrystallized from ethyl acetate to afford 60 mg of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-4-hydroxy-cyclohexyl)amide as a white solid. MS: [M+H]+=555.

Workup

  1. customto give a yellow solution
  2. stirringThe reaction mixture was stirred at room temperature for 24 h
  3. washwashed with water
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 0% to 5% MeOH in DCM)
  7. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-92ddcd594a724f619620e8cf6bebffac
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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