Diisopropylethylamine → HCID 178519939, compound

HRID 336348Notes

Reaction equation

HRID 336348 reaction equation
C(N(C(C)C)CC)(C)C.[F:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[F:21])[N:17]=[C:16]([C:22]([OH:24])=O)[C:15]([OH:25])=[N:14]2.[Cl:26][C:27]1[CH:28]=[C:29]([CH:36]=[CH:37][CH:38]=1)[CH2:30][CH:31]1[CH2:35][CH2:34][CH2:33][NH:32]1>CN(C=O)C>[Cl:26][C:27]1[CH:28]=[C:29]([CH:36]=[CH:37][CH:38]=1)[CH2:30][CH:31]1[CH2:35][CH2:34][CH2:33][N:32]1[C:22]([C:16]1[C:15]([OH:25])=[N:14][C:13]2[C:18](=[CH:19][C:20]([F:21])=[C:11]([F:10])[CH:12]=2)[N:17]=1)=[O:24]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 4269581HCID 4269581, compoundHCID 178524852HCID 178524852, compound

Product 1

HCID 178519939HCID 178519939, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Diisopropylethylamine (0.32 mL, 1.8 mmol) was added dropwise to a mixture of 6,7-difluoro-3-hydroxyquinoxaline-2-carboxylic acid (100 mg, 0.44 mmol), racemic 2-(3-chlorobenzyl)pyrrolidine (72 mg, 0.37 mmol) and O-HATU (210 mg, 0.55 mmol) in anhydrous DMF (2.0 mL) at room temperature under nitrogen, after which the mixture was heated to 85° C. and stirred for 4 h. The cooled mixture was directly purified by flash column chromatography on silica gel, eluting with 10% concentrated ammonium hydroxide in methanol/methylene chloride (gradient from 2:98 to 10:90), to provide a yellow solid. The residue was further purified by preparative reverse phase HPLC to provide (+/−)-[2-(3-chlorobenzyl)pyrrolidin-1-yl](6,7-difluoro-3-hydroxyquinoxalin-2-yl)methanone as a light yellow solid: 1H NMR (400 MHz, CDCl3, ˜2:1 mixture of rotamers) δ 7.72-7.63 (m, 2H, rotamers A and B), 7.38-7.21 (m, 2H, rotamers A and B), 7.10-7.03 (m, 1H, rotamers A and B), 6.90-6.79 (m, 1H, rotamers A and B), 4.63-4.56 (m, 1H, rotamers A and B), 3.89-3.82 (m, 1H, rotamer B), 3.76-3.69 (m, 1H, rotamer A), 3.56-3.47 (m, 1H, rotamers A and B), 3.33 (dd, 1H, rotamer A), 3.17 (q, 1H, rotamer B), 2.94-2.89 (m, 1H, rotamer A), 2.86-2.63 (m, 1H, rotamer B), 2.12-1.92 (m, 2H, rotamers A and B), 1.91-1.73 (m, 2H, rotamers A and B) ppm; ESI MS m/z 404 [M+H]+.

Workup

  1. customThe cooled mixture was directly purified by flash column chromatography on silica gel
  2. washeluting with 10% concentrated ammonium hydroxide in methanol/methylene chloride (gradient from 2:98 to 10:90)
  3. customto provide a yellow solid
  4. customThe residue was further purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-e0d92691677e4b2bad7c8e6d54bd5639
Source dataset
uspto-grants-2014_11
Patent number
US08889683B2

Reaction notes

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