1,2-Dichloroethane → 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246076Notes

Reaction equation

HRID 246076 reaction equation
F[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([C:13]1[N:14]=[C:15]3[C:21]([C:22]([OH:24])=O)=[CH:20][N:19]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:16]3=[N:17][CH:18]=1)=[N:5][N:6]2[CH3:12].C1C=[CH:35][C:36]2[N:41](O)N=N[C:37]=2C=1.C(Cl)CCl.C(N)(C)C.[CH:51](N(CC)C(C)C)(C)C.CN([CH:63]=[O:64])C>>[CH:36]([NH:41][C:22]([C:21]1[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:4]3[C:3]4[C:7](=[CH:8][C:9]([F:11])=[CH:10][CH:2]=4)[N:6]([CH:12]4[CH2:63][O:64][CH2:51]4)[N:5]=3)[N:14]=2)[N:19]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:31])[CH3:32])[CH:20]=1)=[O:24])([CH3:37])[CH3:35]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 6363IsopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712797012-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712796982-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamideYield 78%

Procedure

To a solution of 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (115 mg, 0.23 mmol), HOBt (92 mg, 0.55 mmol) and EDC (105 mg, 0.55 mmol) in DMF (3 ml) was added isopropylamine (41 ul, 0.48 mmol) and N,N-diisopropylethylamine (0.17 ml, 0.95 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with 10% citric acid, sat NaHCO3, sat LiCl, and brine then dried over MgSO4 and concentrated. The residue was chromatographed over silica gel with 20% to 100% EtOAc/heptane to afford 98 mg (78%) of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a white solid.

Workup

  1. customthen quenched with water
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with 10% citric acid
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed over silica gel with 20% to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-91a3eca142a94de293f3964fa86e8b62
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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