Bicarbonate Ion → 6-(4'-t-Butoxycarbonylamino-1'-oxo-butylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole

HRID 395954Notes

Reaction equation

HRID 395954 reaction equation
ClC([O:4][CH2:5][CH:6]([CH3:8])C)=O.[C:9]([O:13][C:14](CCC(N)C(O)=O)=[O:15])([CH3:12])([CH3:11])[CH3:10].[CH3:23][N:24]1CCOCC1.[NH2:30][C:31]1[N:39]=[C:38]2[C:34]([C:35]([C:47]3[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=3)=[C:36]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)[NH:37]2)=[CH:33][CH:32]=1.C(=O)(O)[O-]>C1COCC1>[C:9]([O:13][C:14]([NH:24][CH2:23][CH2:8][CH2:6][C:5]([NH:30][C:31]1[N:39]=[C:38]2[C:34]([C:35]([C:47]3[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=3)=[C:36]([C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)[NH:37]2)=[CH:33][CH:32]=1)=[O:4])=[O:15])([CH3:10])([CH3:11])[CH3:12]

Participants

7

Reactant 5

HCID 769Bicarbonate IonHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 34318522241393-62-2HCID 9926492HCID 9926492, compound

Product 1

HCID 181752196-(4'-t-Butoxycarbonylamino-1'-oxo-butylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

General Procedure for mixed anhydride coupling—Isobutyl chloroformate (32 ml, 0.24 mmol) was added dropwise to a −20-30° C. solution of 4-t-butoxycarbonyl aminobutyric acid (19) (50.1 mg, 0.247 mmol), 4-methylmorpholine (124 ml, 1.23 mmol), and THF (2 mL). After 20 min at −20-30° C., 6-Amino-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (17) (75 mg, 0.24 mmol) and THF (3 mL) was added in one portion. The reaction was allowed to warm to 23° C. After 16 h at 23° C., the reaction was poured into saturated bicarbonate (80 mL), extracted with ethyl acetate (2×100 mL), washed with brine (1×100 mL), and dried (Na2SO4). After concentration in vacuo, the residue was purified by application to two preparative chromatography plates (silica gel 2 mm thickness, 100% ethyl acetate) to afford 6-(4′-t-butoxycarbonylamino-1′-oxo-butylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (20) as a solid: Mass Spectrum (CI) 489 (MH+). Ethyl chloroformate can be used in place of isobutyl chloroformate in this process.

Workup

  1. waitAfter 16 h at 23° C.
  2. extractionextracted with ethyl acetate (2×100 mL)
  3. washwashed with brine (1×100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationAfter concentration in vacuo
  6. customthe residue was purified by application to two preparative chromatography plates (silica gel 2 mm thickness, 100% ethyl acetate)

Sources & evidence

ORD record
ord-9233a47d97aa45b2be3c79e72d40b5ac
Source dataset
uspto-grants-2003_08
Patent number
US06605634B2

Reaction notes

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