Tert-Butylamine → N-tert-Butyl-2-(6-fluoro-1-(2-morpholino-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246269Notes

Reaction equation

HRID 246269 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([C:29]([OH:31])=O)=[CH:27][N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:52]([NH2:56])([CH3:55])([CH3:54])[CH3:53]>C1COCC1>[C:52]([NH:56][C:29]([C:28]1[C:22]2[C:23](=[N:24][CH:25]=[C:20]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH2:11][C:12]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[O:13])[N:7]=3)[N:21]=2)[N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:37])([CH3:38])[CH3:39])[CH:27]=1)=[O:31])([CH3:55])([CH3:54])[CH3:53]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 682631,1'-CarbonyldiimidazoleHCID 712800952-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280344N-tert-Butyl-2-(6-fluoro-1-(2-morpholino-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

In a 15 ml round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (110 mg, 0.20 mmol) was suspended in THF (3 ml) and 1,1′-carbonyldiimidazole (39 mg, 0.24 mmol) was added. The light yellow suspension was stirred at 60° C. for 45 min during which time all solids dissolved. The reaction mixture was cooled to room temperature, tert-butylamine (0.20 ml, 1.9 mmol) was added, and the reaction was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc) to afford 84 mg (70%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white solid.

Workup

  1. dissolutiondissolved
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringthe reaction was stirred at room temperature overnight
  4. customThe reaction mixture was quenched with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc)

Sources & evidence

ORD record
ord-14ec1fb4e65f476489de835396448f41
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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