Dichloromethane → HCID 89783863, compound

HRID 1056262Notes

Reaction equation

HRID 1056262 reaction equation
Cl.[NH2:2][C:3]1([C:6]2[NH:7][C:8]([C:14]3[CH:23]=[CH:22][CH:21]=[C:20]4[C:15]=3[N:16]=[C:17]([NH:25][CH2:26][C:27]([F:30])([F:29])[F:28])[C:18]([CH3:24])=[N:19]4)=[CH:9][C:10]=2[C:11](O)=[O:12])[CH2:5][CH2:4]1.C(Cl)Cl.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>CCOC(C)=O.CN(C=O)C>[CH3:24][C:18]1[C:17]([NH:25][CH2:26][C:27]([F:29])([F:30])[F:28])=[N:16][C:15]2[C:20](=[CH:21][CH:22]=[CH:23][C:14]=2[C:8]2[NH:7][C:6]3[C:3]4([CH2:5][CH2:4]4)[NH:2][C:11](=[O:12])[C:10]=3[CH:9]=2)[N:19]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 89783703HCID 89783703, compound

Product 1

HCID 89783863HCID 89783863, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(3-carboxy-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrolo-2-yl)cyclopropanaminium chloride (381b, 800 mg, 1.81 mmol) was treated with DCM (15 mL) and DMF (15.00 mL) followed by DIEA (1.27 mL, 7.24 mmol) and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (1131 mg, 2.17 mmol). The reaction mixture was then stirred at RT for 15 min. It was diluted with EtOAc (100 mL) and washed with a saturated solution of NaHCO3, and brine (3×50 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by silica gel chromatography (0-20% MeOH in DCM) twice to give 2′-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1′H-spiro[cyclopropane-1,6′-pyrrolo[3,4-b]pyrrol]-4′(5′H)-one (381) (62 mg, 0.16 mmol, 9% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.60 (1H, s), 7.87 (1H, d, J=6.8 Hz), 7.72 (1H, t, J=6.3 Hz), 7.62-7.70 (2H, m), 7.44 (1H, t, J=7.8 Hz), 6.90-6.97 (1H, m), 4.31-4.45 (2H, m), 2.59 (3H, s), 1.36-1.45 (2H, m), 1.26 (2H, d, J=5.9 Hz). 19F NMR (376 MHz, DMSO-d6) δ ppm −69.21 (1F, s), −69.64 (1F, s), −71.10 (1F, s). m/z (ESI, +ve ion) 388.0 (M+H)+.

Workup

  1. washwashed with a saturated solution of NaHCO3, and brine (3×50 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by silica gel chromatography (0-20% MeOH in DCM) twice

Sources & evidence

ORD record
ord-eeb1f17d25e0431386bfb5891b8585ed
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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