Diisopropylethylamine → HCID 89784119, compound

HRID 1056156Notes

Reaction equation

HRID 1056156 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.Cl.[NH2:35][CH2:36][C:37]1[NH:38][C:39]([C:45]2[CH:54]=[CH:53][CH:52]=[C:51]3[C:46]=2[N:47]=[C:48]([NH:56][CH2:57][C:58]([F:61])([F:60])[F:59])[C:49]([CH3:55])=[N:50]3)=[CH:40][C:41]=1[C:42]([OH:44])=O.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:55][C:49]1[C:48]([NH:56][CH2:57][C:58]([F:61])([F:60])[F:59])=[N:47][C:46]2[C:51](=[CH:52][CH:53]=[CH:54][C:45]=2[C:39]2[NH:38][C:37]3[CH2:36][NH:35][C:42](=[O:44])[C:41]=3[CH:40]=2)[N:50]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 89784290HCID 89784290, compound

Product 1

HCID 89784119HCID 89784119, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (AK Scientific, Inc., Union City, Calif.) (415 mg, 0.80 mmol) was added to a solution of 2-(aminomethyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (301c) (255 mg, 0.61 mmol) and DIPEA (Sigma-Aldrich) (0.43 mL, 2.45 mmol) in CH2Cl2 (15 mL) and DMF (15 mL) at RT. After 30 min the reaction mixture was concentrated. EtOAc and H2O were added and the layers were separated. The aq. layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-5% MeOH in CH2Cl2), to provide a yellow solid. The combined fractions were triturated with CH2Cl2 and the solid was collected by filtration and washed with CH2Cl2 and Et2O to provide 2-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (301) (48 mg, 0.13 mmol, 22% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.97 (br. s., 1H), 7.89 (d, J=7.04 Hz, 1H), 7.74 (t, J=6.55 Hz, 1H), 7.67 (d, J=8.22 Hz, 1H), 7.52 (br. s., 1H), 7.39-7.47 (m, 1H), 6.97 (s, 1H), 4.33-4.46 (m, 2H), 4.25 (br. s., 2H), 2.59 (s, 3H). 19F NMR (376 MHz, DMSO-d6) δ ppm −69.44 (s, 3F). m/z (ESI, +ve) 362.0 (M+H)+.

Workup

  1. concentrationAfter 30 min the reaction mixture was concentrated
  2. additionEtOAc and H2O were added
  3. customthe layers were separated
  4. extractionThe aq. layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by silica gel chromatography (0-5% MeOH in CH2Cl2)
  10. customto provide a yellow solid
  11. customThe combined fractions were triturated with CH2Cl2
  12. filtrationthe solid was collected by filtration
  13. washwashed with CH2Cl2 and Et2O

Sources & evidence

ORD record
ord-248cf43ee39f43f1b3f22f83ea37e153
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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