Methanol → HCID 86279021, compound

HRID 588880Notes

Reaction equation

HRID 588880 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([NH:11][CH2:12][C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:24][N:23]([C:25](=[O:28])[CH:26]=[CH2:27])[CH2:22]3)[CH2:17][CH2:16]2)=[O:14])=[C:4]([O:29]C)[CH:3]=1.B(Br)(Br)Br.CO.CCN(CC)CC>C(Cl)Cl.O>[Cl:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([NH:11][CH2:12][C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:24][N:23]([C:25](=[O:28])[CH:26]=[CH2:27])[CH2:22]3)[CH2:17][CH2:16]2)=[O:14])=[C:4]([OH:29])[CH:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 25134Boron tribromideHCID 90461841HCID 90461841, compound

Product 1

HCID 86279021HCID 86279021, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-(4-(2-(4-chloro-5-isopropyl-2-methoxyphenylamino)acetyl)piperazin-1-yl)azetidin-1-yl)prop-2-en-1-one (77 mg, 0.18 mmol) in DCM (15 mL) at −60° C., BBr3 (443 mg, 1.8 mmol) was added dropwise and the resulting mixture was stirred at RT for 1 h. The mixture was cooled to −60° C., MeOH was added dropwise and then basified with Et3N to adjust the pH to 8-9. The mixture was poured into water and extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1) to afford the desired product (25 mg, 33% yield). 1H NMR (400 MHz, DMSO-d6) δ: 9.50 (bs, 1H), 6.62 (s, 1H), 6.470 (s, 1H), 6.30 (m, 1H), 6.10 (dd, J=2.4, 17.2 Hz, 1H), 5.68 (dd, J=2.0, 10.4 Hz, 1H), 5.14 (m, 1H), 4.25 (m, 1H), 4.06 (m, 1H), 3.96 (m, 1H), 3.91 (m, 2H), 3.78 (m, 1H), 3.54 (m, 4H), 3.17 (m, 2H), 2.35 (m, 4H), 1.21 (m, 6H). ESI-MS m/z: 421.4[M+H]+.

Workup

  1. temperatureThe mixture was cooled to −60° C.
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1)

Sources & evidence

ORD record
ord-17687b6263c14c0285d4f3366901aa3b
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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