2-(Dimethylamino)ethanol → HCID 70961728, compound

HRID 1394951Notes

Reaction equation

HRID 1394951 reaction equation
[CH:1]1([C@H:4]([NH:26][C:27](=[O:38])[O:28][C:29]2C=CC([N+]([O-])=O)=C[CH:30]=2)[C:5]([N:7]2[CH2:11][C:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])=[CH:9][C@H:8]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:39][N:40](C)[CH2:41]CO>>[CH:1]1([C@H:4]([NH:26][C:27](=[O:38])[O:28][CH2:29][CH2:30][N:40]([CH3:41])[CH3:39])[C:5]([N:7]2[CH2:11][C:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])=[CH:9][C@H:8]2[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:6])[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 79022-(Dimethylamino)ethanolHCID 58641354HCID 58641354, compound

Product 1

HCID 70961728HCID 70961728, compound

Procedure

A solution of (1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethylcarbamate (31-1, 50 mg, 0.096 mmol) in 2-(dimethylamino)ethanol (1 mL) was heated at 100° C. for 1 hour. The reaction mixture was cooled, then partitioned between ethyl acetate (40 mL) and brine (3×40 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography (EtOAc initially, grading to 10% saturated NH3/ethanol in EtOAc) to give 2-(dimethylamino)ethyl(1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethylcarbamate (31-2) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) showed a 2:1 mixture of rotamers; major rotamer: δ 7.42-7.24 (m, 5H), 7.11-6.95 (m, 3H), 6.41 (br s, 1H), 5.93 (m, 1H), 5.58 (d, 1H, J=7.6 Hz), 5.04 (br d, 1H, J=13.9 Hz), 4.91 (ddd, 1H, J=14.7, 4.4, 1.7 Hz), 4.30 (t, 1H, J=7.8 Hz), 4.15 (m, 2H), 2.54 (m, 2H), 2.27 (s, 6H), 1.14 (m, 1H), 0.57-0.33 (m, 4H). LRMS nil/z (M+H) 470.5 found, 470.2 required.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate (40 mL) and brine (3×40 mL)
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (EtOAc initially

Sources & evidence

ORD record
ord-98255f714e144481a030e470e804010c
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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