1-Hydroxybenzotriazole → HCID 86677960, compound

HRID 246220Notes

Reaction equation

HRID 246220 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH:11]1[CH2:13][CH:12]1[C:14]#[N:15])[CH3:10].ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[Cl:35][C:36]1[CH:44]=[C:43]2[C:39]([C:40]([C:46]3[N:47]=[C:48]4[C:54]([C:55](O)=[O:56])=[CH:53][N:52]([CH2:58][O:59][CH2:60][CH2:61][Si:62]([CH3:65])([CH3:64])[CH3:63])[C:49]4=[N:50][CH:51]=3)=[N:41][N:42]2[CH3:45])=[CH:38][CH:37]=1>C(OCC)(=O)C.O.CN(C=O)C>[C:14]([CH:12]1[CH2:13][CH:11]1[C@H:9]([NH:8][C:55]([C:54]1[C:48]2[C:49](=[N:50][CH:51]=[C:46]([C:40]3[C:39]4[C:43](=[CH:44][C:36]([Cl:35])=[CH:37][CH:38]=4)[N:42]([CH3:45])[N:41]=3)[N:47]=2)[N:52]([CH2:58][O:59][CH2:60][CH2:61][Si:62]([CH3:65])([CH3:64])[CH3:63])[CH:53]=1)=[O:56])[CH3:10])#[N:15]

Participants

8

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 71279685HCID 71279685, compound

Product 1

HCID 86677960HCID 86677960, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-((R)-1-Amino-ethyl)-cyclopropanecarbonitrile trifluoroacetate, diastereomer A (crude from Step 2) was treated with 1-hydroxybenzotriazole (153 mg, 1.14 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (662 mg, 1.75 mmol,), DIPEA (0.76 ml, 4.37 mmol), 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (400 mg, 0.87 mmol) and DMF (6.0 ml) to give a light yellow solution. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and water. The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, EtOAc in heptane gradient) to provide 210 mg (44%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(2-cyano-cyclopropyl)-ethyl]-amide (diastereomer A) as a colorless oil. MS: (M+H)+=551.

Workup

  1. customto give a light yellow solution
  2. dry with materialThe organic layers were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 40 g, EtOAc in heptane gradient)

Sources & evidence

ORD record
ord-c78540d0457d4772b39ff4915366b59d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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