Diisopropylethylamine → HCID 71731518, compound

HRID 1056136Notes

Reaction equation

HRID 1056136 reaction equation
Cl.[NH2:2][C:3]1([C:6]2[NH:7][C:8]([C:14]3[C:23]([F:24])=[CH:22][CH:21]=[C:20]4[C:15]=3[N:16]=[C:17]([NH:26][CH:27]3[CH2:29][CH2:28]3)[C:18]([CH3:25])=[N:19]4)=[CH:9][C:10]=2[C:11]([OH:13])=O)[CH2:5][CH2:4]1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[CH:27]1([NH:26][C:17]2[C:18]([CH3:25])=[N:19][C:20]3[C:15]([N:16]=2)=[C:14]([C:8]2[NH:7][C:6]4[C:3]5([CH2:5][CH2:4]5)[NH:2][C:11](=[O:13])[C:10]=4[CH:9]=2)[C:23]([F:24])=[CH:22][CH:21]=3)[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 89783657HCID 89783657, compound

Product 1

HCID 71731518HCID 71731518, compoundYield 50.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a 50-mL round-bottomed flask was added 2-(1-aminocyclopropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (283e; 0.30 g, 0.718 mmol), DIEA (Aldrich) (0.75 mL, 4.31 mmol) in DMF (1.8 mL) and DCM (1.8 mL). Then 1H-benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) (Matrix innovation, Quebec City, Canada) (0.45 g, 0.86 mmol) was added into the reaction mixture. The overall mixture was stirred under inert atmosphere 40 min. The mixture was partially concentrated (removed DCM) in vacuo, then diluted with water and stirred 10 min. The precipitate was collected by filtration. The solids were triturated from hot EtOH in a sealed tube. The solids were collected by filtration, washed with Et2O, and dried in a reduced pressure oven (40° C.) overnight. This gave 2′-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1′H-spiro[cyclopropane-1,6′-pyrrolo[3,4-b]pyrrol]-4′(5′H)-one (283) (0.13 g, 0.36 mmol, 50% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.61 (br. S, 1H), 7.74 (br. s, 1H), 7.62-7.70 (m, 2H), 6.92 (br. s, 1H), 1.38-1.45 (m, 2H), 1.35 (br. s, 3H), 0.75-0.84 (m, 2H), 0.72 (br. s, 4H). m/z (ESI, +ve) 364 (M+H).

Workup

  1. concentrationThe mixture was partially concentrated
  2. custom(removed DCM) in vacuo
  3. additiondiluted with water
  4. stirringstirred 10 min
  5. filtrationThe precipitate was collected by filtration
  6. customThe solids were triturated from hot EtOH in a sealed tube
  7. filtrationThe solids were collected by filtration
  8. washwashed with Et2O
  9. customdried in a reduced pressure oven (40° C.) overnight

Sources & evidence

ORD record
ord-c75b2c89e82c445dabb51d9b522aa027
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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