Glycerol → HCID 66891596, compound

HRID 532825Notes

Reaction equation

HRID 532825 reaction equation
[CH3:1][O:2][C:3]1[C:4]([N:10]2[CH2:16][CH2:15][CH2:14][N:13]([CH2:17][C:18]3[S:22][C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:20][CH:19]=3)[CH2:12][CH2:11]2)=[C:5]([NH2:9])[CH:6]=[CH:7][CH:8]=1.[N+]([C:32]1[CH:33]=C(S([O-])(=O)=O)C=C[CH:37]=1)([O-])=O.[Na+].OCC(CO)O.[OH-].[Na+]>CS(O)(=O)=O.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[C:4]([N:10]2[CH2:16][CH2:15][CH2:14][N:13]([CH2:17][C:18]3[S:22][C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:20][CH:19]=3)[CH2:12][CH2:11]2)=[C:5]2[C:6]([CH:37]=[CH:32][CH:33]=[N:9]2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 753GlycerolHCID 14798Sodium HydroxideHCID 31389Sodium 3-nitrobenzenesulfonateHCID 66892876HCID 66892876, compound

Product 1

HCID 66891596HCID 66891596, compoundYield 87.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6395Methanesulfonic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3-methoxy-2-[4-(2-phenylthiazol-5-ylmethyl)-[1,4]diazepan-1-yl]-phenylamine (210 mg, 0.53 mmol, 1 equiv), sodium 3-nitrophenylsulfonate (78 mg, 0.65 equiv), FeSO4.7H2O (7.5 mg, 0.05 equiv) and glycerol (122 mg, 2.5 equiv) in 2 mL of methanesulfonic acid was heated at 130° C. for 2 hours. After cooling down to room temperature, the mixture was diluted with water, neutralized with 10 N NaOH to pH˜10. Ethyl acetate was added and the mixture was filtered through celite. The organic layer was subjected to reverse phase HPLC purification. The combined fractions with the desired product were evaporated to remove acetonitrile, treated with saturated sodium bicarbonate and extracted with ethyl acetate to give the pure title compound (130 mg, 56%). 1H NMR (400 MHz, CDCl3) δ 8.85 (dd, 1H, J=4.1, 2 Hz), 8.05 (dd, 1H, J=7.8, 2 Hz), 7.95 (d, 1H, J=2 Hz), 7.90 (d, 1H, J=2 Hz), 7.50 (d, 1H, 8.6 Hz), 7.42-7.35 (m, 3H), 7.30-7.20 (m, 3H), 7.20 (dd, 1H, J=7.8, 4.1 Hz), 4.08 (s, 2H), 3.85 (s, 3H), 3.62-3.50 (m, 4H), 3.10-3.00 (m, 2H), 3.00-2.80 (m, 2H), 2.20-2.00 (m, 2H). MS (ES) m/z 431.1 (M+H+).

Workup

  1. temperatureAfter cooling down to room temperature
  2. filtrationthe mixture was filtered through celite
  3. customphase HPLC purification
  4. customThe combined fractions with the desired product were evaporated
  5. customto remove acetonitrile
  6. additiontreated with saturated sodium bicarbonate
  7. extractionextracted with ethyl acetate

Sources & evidence

ORD record
ord-8ee2b774e67f481bada9d053c9d57b34
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

Loading…