Methanol → HCID 136341339, compound

HRID 579314Notes

Reaction equation

HRID 579314 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][C:15]([OH:19])=[CH:16]2)=[CH:11][C:10]=1[C:20]1[S:21][C:22]([N:25]([CH3:36])[CH:26]2[CH2:31][C:30]([CH3:33])([CH3:32])[NH:29][C:28]([CH3:35])([CH3:34])[CH2:27]2)=[N:23][N:24]=1)C1C=CC=CC=1.B(Br)(Br)Br.CO>C(Cl)Cl>[CH3:36][N:25]([CH:26]1[CH2:31][C:30]([CH3:33])([CH3:32])[NH:29][C:28]([CH3:35])([CH3:34])[CH2:27]1)[C:22]1[S:21][C:20]([C:10]2[C:9]([OH:8])=[CH:18][C:17]3[C:12]([CH:11]=2)=[CH:13][CH:14]=[C:15]([OH:19])[CH:16]=3)=[N:24][N:23]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 136341340HCID 136341340, compound

Product 1

HCID 136341339HCID 136341339, compoundYield 49.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred, ice-bath cooled suspension of 7-(benzyloxy)-6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-2-ol (49 mg, 0.112 mmol) in DCM (2 ml) under nitrogen was added BBr3 (1M solution in DCM, 0.56 mL, 0.56 mmol). The reaction mixture was quenched by addition of MeOH (2 mL) and the resulting solution was warmed to room temperature, then loaded onto a 1 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (˜15 mL) then flushed with 7M NH3 in MeOH (˜10 mL). The MeOH/NH3 was removed in vacuo to afford the crude product. The crude product was taken up in 1:1 MeOH:DMSO (2 mL), filtered via syringe filter, and the filtrate purified by preparative HPLC, under neutral conditions, running a gradient from 10-90% MeCN/water over 15 minutes. The relevant fractions were combined and concentrated in vacuo to afford the title compound as a dark green/brown solid (20.6 mg, 49.2% yield). LC-MS: Rt 0.85 min; MS m/z 413.3 [M+H]+ [Method B]. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.92 (br. s., 1H) 9.81 (br. s., 1H) 8.31 (s, 1H) 7.74 (d, J=9.09 Hz, 1H) 7.07 (s, 1H) 6.87-6.94 (m, 2H) 4.25-4.34 (m, 1H) 3.01 (s, 3H) 1.64 (dd, J=12.13, 3.03 Hz, 2H) 1.45 (t, J=12.13 Hz, 2H) 1.22 (s, 6H) 1.10 (s, 6H).

Workup

  1. temperatureTo a stirred, ice-bath cooled
  2. customThe reaction mixture was quenched by addition of MeOH (2 mL)
  3. washThe cartridge was washed with MeOH (˜15 mL)
  4. customthen flushed with 7M NH3 in MeOH (˜10 mL)
  5. customThe MeOH/NH3 was removed in vacuo
  6. customto afford the crude product
  7. filtrationDMSO (2 mL), filtered via syringe
  8. filtrationfilter
  9. customthe filtrate purified by preparative HPLC, under neutral conditions
  10. customover 15 minutes
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-59c74b723c7a493fb7d70a80098be900
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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