Diisopropylethylamine → HCID 25126143, compound

HRID 1875002Notes

Reaction equation

HRID 1875002 reaction equation
[Br:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:43][CH2:44][C:45]1[C:46]([F:62])=[C:47]([O:52][C:53]2[CH:54]=[C:55]([CH:58]=[C:59]([Cl:61])[CH:60]=2)[C:56]#[N:57])[C:48]([Cl:51])=[CH:49][CH:50]=1>CN(C=O)C.CCOC(C)=O.O>[Br:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[C:7]([NH:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([O:52][C:53]2[CH:54]=[C:55]([C:56]#[N:57])[CH:58]=[C:59]([Cl:61])[CH:60]=2)[C:46]=1[F:62])=[O:9]

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 538307483-broMo-1H-Pyrrole-2-carboxylic acidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 25126143HCID 25126143, compoundYield 8.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-1H-pyrrole-2-carboxylic acid (0.2 g, 0.684 mmol) in DMF (2 mL) was added HATU (0.48 g, 1.262 mmol), DIPEA (0.270 ml, 1.547 mmol) and 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.39 g, 1.253 mmol). The reaction mixture was stirred at RT overnight. Water (5 ml) and EtOAc (10 mL) were added and the layers separated. The aqueous layer was extracted with EtOAc (3×10 mL), the organic layers combined, dried over sodium sulfate, filtered and evaporated. Purification was accomplished by RPHPLC. Further purification by RPHPLC was required. The desired fractions were collected, neutralized with sat. sodium bicarbonate and extracted with EtOAc (3×10 mL). The organic layers were combined, dried over sodium sulfate, filtered and evaporated to afford 3-bromo-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-pyrrole-2-carboxamide (0.029 g, 8.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.87 (br. s., 1H) 7.96 (t, 1H) 7.83 (s, 1H) 7.46-7.54 (m, 3H) 7.40 (t, 1H) 6.96 (t, 1H) 6.25 (t, 1H) 4.56 (d, 2H). MS: m/z 479.9 (M−1).

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customPurification
  7. customFurther purification by RPHPLC
  8. customThe desired fractions were collected
  9. extractionextracted with EtOAc (3×10 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-44c78c1f74324536a8db6abf71a1db41
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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