Diisopropylethylamine → HCID 71286094, compound

HRID 246009Notes

Reaction equation

HRID 246009 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@H:9]([NH2:11])[CH3:10].C(N(CC)C(C)C)(C)C.[F:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([C:32]3[N:33]=[C:34]4[C:40]([C:41](O)=[O:42])=[CH:39][N:38]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[C:35]4=[N:36][CH:37]=3)=[N:27][N:28]2[CH3:31])=[CH:24][CH:23]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@H:9]([NH:11][C:41]([C:40]1[C:34]2[C:35](=[N:36][CH:37]=[C:32]([C:26]3[C:25]4[C:29](=[CH:30][C:22]([F:21])=[CH:23][CH:24]=4)[N:28]([CH3:31])[N:27]=3)[N:33]=2)[N:38]([CH2:44][O:45][CH2:46][CH2:47][Si:48]([CH3:51])([CH3:50])[CH3:49])[CH:39]=1)=[O:42])[CH3:10]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56973375(1R)-1-(Pyridin-2-yl)ethan-1-amine--hydrogen chloride (1/2)HCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71286094HCID 71286094, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-1-pyridin-2-yl-ethylamine dihydrochloride (66 mg, 0.34 mmol) in DMF (2 mL) was added N,N-diisopropylethylamine (0.20 mL, 1.13 mmol), 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.23 mmol), and HATU (95 mg, 0.25 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes to give 117 mg (95%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-pyridin-2-yl-ethyl)-amide as a white solid.

Workup

  1. customthen quenched with water
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organics were washed with water (3×) and brine
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-94c03a6c653741caa3457d5d3789e141
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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