Diisopropylethylamine → 9-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid (2-amino-4-fluorophenyl)amide

HRID 1925563Notes

Reaction equation

HRID 1925563 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[C:6]([C:11]([OH:13])=O)[CH:7]=[CH:8][CH:9]=2)[N:4]2[CH:14]=[CH:15][CH:16]=[C:3]12.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[F:50][C:51]1[CH:56]=[CH:55][C:54]([NH2:57])=[C:53]([NH2:58])[CH:52]=1>O1CCCC1>[NH2:58][C:53]1[CH:52]=[C:51]([F:50])[CH:56]=[CH:55][C:54]=1[NH:57][C:11]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[N:4]1[CH:14]=[CH:15][CH:16]=[C:3]1[C:2]2=[O:1])=[O:13]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1645844-Fluorobenzene-1,2-diamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672992929-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid

Product 1

HCID 672992369-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid (2-amino-4-fluorophenyl)amideYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 250 ml round-bottomed flask under argon, a mixture of 620 mg of 9-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid obtained according to the preceding stage, 1.50 g of o-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) and 0.44 ml of diisopropylethylamine in 55 ml of tetrahydrofuran is stirred at ambient temperature for 1 hour. 367 mg of 4-fluoro-o-phenylenediamine are then added and the stirring is maintained for 3 days. The reaction medium is evaporated to dryness under vacuum and the residue is taken up with 15 ml of a mixture of dichloromethane and methanol (90/10 v/v). The organic phase is washed with 10 ml of a saturated solution of sodium bicarbonate, then with 3 times 5 ml of distilled water, and dried over magnesium sulphate. After evaporation to dryness under vacuum, the residue is loaded as a dry spot onto a column of silica gel (40-63 μm) and chromatographed, elution being carried out with a mixture of dichloromethane and methanol (95/5 v/v). 379 mg of 9-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid (2-amino-4-fluorophenyl)amide are obtained in the form of a beige solid, the characteristics of which are the following:

Workup

  1. customobtained
  2. temperaturethe stirring is maintained for 3 days
  3. customThe reaction medium is evaporated to dryness under vacuum
  4. washThe organic phase is washed with 10 ml of a saturated solution of sodium bicarbonate
  5. dry with materialwith 3 times 5 ml of distilled water, and dried over magnesium sulphate
  6. customAfter evaporation to dryness under vacuum
  7. customchromatographed
  8. washelution
  9. additionbeing carried out with a mixture of dichloromethane and methanol (95/5 v/v)

Sources & evidence

ORD record
ord-5b06b3cae5d94acd84d418e2ae9526f4
Source dataset
uspto-grants-2012_05
Patent number
US08178687B2

Reaction notes

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