Methyl iodide → HCID 89783995, compound

HRID 1056350Notes

Reaction equation

HRID 1056350 reaction equation
[C:1]([NH:5][C:6]1[C:7]([CH3:27])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:20][C:19]3[C@H:21]([CH2:25][OH:26])[NH:22][C:23](=[O:24])[C:18]=3[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].[C:28](NC1C(C)=NC2C(N=1)=C(C1NC3[C@@H](CO)NC(=O)C=3C=1)C=CC=2)(C)(C)C.[H-].[Na+].CI>C1COCC1.CN(C=O)C>[C:1]([NH:5][C:6]1[C:7]([CH3:27])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[N:20]([CH3:28])[C:19]3[CH:21]([CH2:25][OH:26])[NH:22][C:23](=[O:24])[C:18]=3[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 89783616HCID 89783616, compoundHCID 89783694HCID 89783694, compound

Product 1

HCID 89783995HCID 89783995, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 25-mL round-bottomed flask was added (R)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6-(hydroxymethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one and (S)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6-(hydroxymethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (469) (36 mg, 0.1 mmol), DMF (1 mL) and THF (1 mL). To the yellow suspension NaH (4 mg, 0.1 mmol, 60% in mineral oil) was added at RT. The reaction mixture was stirred at RT for 15 min and MeI (6 μt, 0.1 mmol) was added. The reaction mixture was stirred at RT for 1 h and the solvent was completely removed under vacuum. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 3-8% MeOH in DCM to provide 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6-(hydroxymethyl)-1-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (470) (28 mg, 75% yield, 50% ee) as a light yellow solid and a mixture of enantiomers. 1H NMR (400 MHz, DMSO-d6) δ 7.78 (dd, J=1.47, 8.12 Hz, 1H), 7.43-7.51 (m, 2H), 7.33-7.39 (m, 1H), 6.10 (s, 1H), 5.88 (s, 1H), 5.15 (t, J=5.38 Hz, 1H), 4.46 (t, J=6.16 Hz, 1H), 3.59 (t, J=5.97 Hz, 2H), 3.32 (s, 3H), 2.52 (s, 3H), 1.29 (s, 9H). m/z (ESI, +ve) 380.1 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at RT for 1 h
  2. customthe solvent was completely removed under vacuum
  3. customThe crude material was absorbed onto a plug of silica gel
  4. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  5. washeluting with a gradient of 3-8% MeOH in DCM

Sources & evidence

ORD record
ord-dd6f0fce712543e496646b74ea5f7731
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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