Boron Trichloride → HCID 89783326, compound

HRID 1056349Notes

Reaction equation

HRID 1056349 reaction equation
C([O:8][CH2:9][C@H:10]1[C:14]2[NH:15][C:16]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[N:20]=[C:21]([NH:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:22]([CH3:28])=[N:23]4)=[CH:17][C:13]=2[C:12](=[O:34])[NH:11]1)C1C=CC=CC=1.C(OC[C@@H]1C2NC(C3C=CC=C4C=3N=C(NC(C)(C)C)C(C)=N4)=CC=2C(=O)N1)C1C=CC=CC=1.B(Cl)(Cl)Cl>C(Cl)Cl>[C:30]([NH:29][C:21]1[C:22]([CH3:28])=[N:23][C:24]2[C:19]([N:20]=1)=[C:18]([C:16]1[NH:15][C:14]3[CH:10]([CH2:9][OH:8])[NH:11][C:12](=[O:34])[C:13]=3[CH:17]=1)[CH:27]=[CH:26][CH:25]=2)([CH3:33])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 25135Boron TrichlorideHCID 89783782HCID 89783782, compoundHCID 89784353HCID 89784353, compound

Product 1

HCID 89783326HCID 89783326, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 100-mL round-bottomed flask was added (6R)-6-((benzyloxy)methyl)-2-(3-(tert-butylamino)-2-methyl-5-quinoxalinyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one and (6S)-6-((benzyloxy)methyl)-2-(3-(tert-butylamino)-2-methyl-5-quinoxalinyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (468) (0.55 g, 1.20 mmol) and DCM (15 mL). The reaction mixture was cooled to 0° C. and under a nitrogen atmosphere boron trichloride (2.40 mL, 2.40 mmol, 1 M in DCM) (Sigma-Aldrich) was added dropwise. The reaction mixture was stirred at 0° C. for 30 min and at RT for 1 h. The reaction was quenched by the addition of NaHCO3 (200 mg in MeOH, 5 mL) and the solvent was 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 0% to 4% 2M NH3/MeOH in DCM to provide 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6-(hydroxymethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (469) (0.25 g, 57% yield, 50% ee) as a yellow solid and as a mixture of enantiomers. 1H NMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H), 7.86 (dd, J=1.37, 7.63 Hz, 1H), 7.63 (dd, J=1.37, 8.02 Hz, 1H), 7.58 (s, 1H), 7.36 (t, J=7.73 Hz, 1H), 6.88 (d, J=1.57 Hz, 1H), 6.02 (s, 1H), 5.09 (t, J=5.58 Hz, 1H), 4.48 (t, J=6.06 Hz, 1H), 3.66 (td, J=5.53, 10.86 Hz, 1H), 3.54 (td, J=6.16, 10.76 Hz, 1H), 2.56 (br. s., 3H), 1.56 (s, 9H). m/z (ESI, +ve) 366.0 (M+H)+.

Workup

  1. additionwas added dropwise
  2. customThe reaction was quenched by the addition of NaHCO3 (200 mg in MeOH, 5 mL)
  3. customthe solvent was removed under vacuum
  4. customThe crude material was absorbed onto a plug of silica gel
  5. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  6. washeluting with a gradient of 0% to 4% 2M NH3/MeOH in DCM

Sources & evidence

ORD record
ord-220ca5c0fcfe4d37b30c287e1be32425
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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