Diisopropylethylamine → HCID 178489062, compound

HRID 2174130Notes

Reaction equation

HRID 2174130 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[C:12]([C:20]([C:25]#[N:26])([CH3:24])[C:21](O)=O)[C:13]([O:18][CH3:19])=[CH:14][C:15]=2[CH3:17])[CH:10]=[CH:9]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:60][C:61]1[CH:62]=[C:63]([NH2:68])[C:64]([NH2:67])=[CH:65][CH:66]=1>C(Cl)Cl>[Br:60][C:61]1[CH:66]=[CH:65][C:64]2[NH:67][C:21]([C:20]([C:12]3[C:13]([O:18][CH3:19])=[CH:14][C:15]([CH3:17])=[C:16]4[C:11]=3[CH:10]=[CH:9][NH:8]4)([CH3:24])[C:25]#[N:26])=[N:68][C:63]=2[CH:62]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3235934-Bromobenzene-1,2-diamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86701773HCID 86701773, compound

Product 1

HCID 178489062HCID 178489062, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (±)-2-(1-(tert-butoxycarbonyl)-5-methoxy-7-methyl-1H-indol-4-yl)-2-cyanopropanoic acid (Example 155-E) (1.4 g, 3.91 mmol) in DCM (39.1 ml) at 0° C. was added DIPEA (2.05 ml, 11.72 mmol) followed by HBTU (1.926 g, 5.08 mmol) and 4-bromobenzene-1,2-diamine (1.096 g, 5.86 mmol) at 0° C. and stirred in the ice bath for 20 minutes. The ice bath was removed and the reaction was stirred at room temperature overnight. The reaction was diluted with water, the layers were separated and the organic layer was dried over Na2SO4 and concentrated. The residue was dissolved in acetic acid (7 mL) and heated at 85° C. for 4 hours. The reaction was cooled to 0° C. and quenched with a saturated solution of sodium bicarbonate, diluted with water and EtOAc. The layers were separated and the organic layer was removed, dried over Na2SO4 and concentrated. The crude product was purified via FCC (0-50% EtOAc:heptanes) to obtain the title compound. MS (ESI+) m/z 409.3, 411.3 (M+H).

Workup

  1. customThe ice bath was removed
  2. additionThe reaction was diluted with water
  3. customthe layers were separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in acetic acid (7 mL)
  7. temperatureheated at 85° C. for 4 hours
  8. temperatureThe reaction was cooled to 0° C.
  9. customquenched with a saturated solution of sodium bicarbonate
  10. additiondiluted with water and EtOAc
  11. customThe layers were separated
  12. customthe organic layer was removed
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated
  15. customThe crude product was purified via FCC (0-50% EtOAc:heptanes)

Sources & evidence

ORD record
ord-874854690ac144be9271c56cc30187d7
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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