Diisopropylethylamine → HCID 71285950, compound

HRID 246224Notes

Reaction equation

HRID 246224 reaction equation
[F: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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[Br:57][C:58]1[CH:59]=[C:60]([C:64]2([NH2:68])[CH2:67][CH2:66][CH2:65]2)[CH:61]=[CH:62][CH:63]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O.CC(=O)OCC>[Br:57][C:58]1[CH:59]=[C:60]([C:64]2([NH:68][C:21]([C:20]3[C:14]4[C:15](=[N:16][CH:17]=[C:12]([C:6]5[C:5]6[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=6)[N:8]([CH3:11])[N:7]=5)[N:13]=4)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])[CH:19]=3)=[O:22])[CH2:67][CH2:66][CH2:65]2)[CH:61]=[CH:62][CH:63]=1

Participants

8

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 468355151-(3-Bromophenyl)cyclobutan-1-amine--hydrogen chloride (1/1)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 71285950HCID 71285950, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (200 mg, 0.45 mmol) in DMF (5 mL) were added HATU (344 mg, 0.91 mmol) and 1-(3-bromo-phenyl)-cyclobutanamine hydrochloride (178 mg, 0.68 mmol) followed by DIPEA (0.40 mL, 2.26 mmol) at room temperature under nitrogen atmosphere. The resulting light yellow solution was stirred for 15 h by which time TLC analysis (Hex:EA, 1:1, Rf=0.5) indicated the presence of a new spot. Then, the reaction mixture was diluted with water and the organic compound was extracted into EtOAc (3×25 mL). The combined extracts were washed with brine solution and then dried over anhydrous MgSO4. Filtration of the drying agent and concentration of the filtrate gave the crude product which was purified using by ISCO column chromatography (40 g) eluting with EtOAc in hexanes (0-60%) in 10 minutes. The desired fractions were combined and the solvent was removed under vacuum to obtain 234 mg (80%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(3-bromophenyl)-cyclobutyl]-amide as a light brown solid.

Workup

  1. extractionthe organic compound was extracted into EtOAc (3×25 mL)
  2. washThe combined extracts were washed with brine solution
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationFiltration of the drying agent and concentration of the filtrate
  5. customgave the crude product which
  6. customwas purified
  7. washeluting with EtOAc in hexanes (0-60%) in 10 minutes
  8. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-310137dbb53844ae85cfd456fd725203
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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