1-Hydroxybenzotriazole → HCID 178481747, compound

HRID 246140Notes

Reaction equation

HRID 246140 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](O)=[O:22])=[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.N1(O)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C@H:51]1([NH2:58])[CH2:56][CH2:55][C@@H:54]([NH2:57])[CH2:53][CH2:52]1>CN(C=O)C.CCOC(C)=O>[NH2:57][C@@H:54]1[CH2:55][CH2:56][C@H:51]([NH:58][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])([CH3:31])[CH3:30])[CH:19]=2)=[O:22])[CH2:52][CH2:53]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 178511673HCID 178511673, compound

Product 1

HCID 178481747HCID 178481747, compoundYield 70.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

In a 20 mL scintillation vial, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.10 g, 0.22 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (91 mg, 0.24 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (33 mg, 0.240 mmol), and N,N-diisopropylethylamine (38 μl, 0.22 mmol) were combined with DMF (4 ml) to give a light yellow solution. The reaction mixture was stirred at room temperature for 45 min. In a 20 mL round-bottomed flask, cis-cyclohexane-1,4-diamine (249 mg, 2.18 mmol) was dissolved in 0.4 mL DMF to give a colorless solution. The carboxylic acid reaction mixture was added dropwise to the amine solution. The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with EtOAc (−50 mL) and washed with sat NaHCO3 (3×25 mL) and H2O (3×25 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by chromatography over SiO2 with 0% to 10% MeOH in DCM with 0.1% NH4OH to afford 86 mg of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-4-amino-cyclohexyl)amide as a white solid. MS: [M+H]+=554.

Workup

  1. customto give a light yellow solution
  2. customto give a colorless solution
  3. stirringThe reaction mixture was stirred at room temperature for 24 h
  4. washwashed
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by chromatography over SiO2 with 0% to 10% MeOH in DCM with 0.1% NH4OH

Sources & evidence

ORD record
ord-bcbf7c820266481e934392fade8ed64f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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