Triethylamine → HCID 136358491, compound

HRID 601323Notes

Reaction equation

HRID 601323 reaction equation
[NH2:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:32])[N:16]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:17]4[C:22]([C:23]=3[OH:24])=[CH:21][CH:20]=[CH:19][CH:18]=4)[NH:7][C:6]=2[S:5][CH:4]=1.C(N(CC)CC)C.N12CCCN=C1CCCCC2.[CH3:51][S:52](Cl)(=[O:54])=[O:53]>O1CCCC1.CN(C)C=O>[CH2:25]([N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:23]([OH:24])=[C:14]([C:8]2[NH:7][C:6]3[S:5][CH:4]=[C:3]([CH2:2][NH:1][S:52]([CH3:51])(=[O:54])=[O:53])[C:11]=3[S:10](=[O:13])(=[O:12])[N:9]=2)[C:15]1=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chloride5×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 136347238HCID 136347238, compound

Product 1

HCID 136358491HCID 136358491, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product of Example 345 (15 mg, 0.032 mmol) in tetrahydrofuran (0.4 mL) was added triethylamine (0.018 mL, 0.129 mmol) followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.018 mL, 0.129 mmol). The mixture was cooled to 0° C. and methanesulfonyl chloride was added (0.003 mL, 0.032 mmol). The mixture was stirred at 0° C. for 2.5 hours and then warmed to 23° C. and stirred for 2.5 hours. Additional 1,8-diazabicyclo[5.4.0]undec-7-ene (0.010 mL 0.064 mmol) and methane sulfonyl chloride (0.003 mL, 0.032 mmol) were added and the mixture was stirred at 23° C. for 15 hours. A few drops of N,N-dimethylformamide were added to increase solubility. Additional methane sulfonyl chloride (0.003 mL, 0.032 mmol) was added and the reaction mixture was stirred at 23° C. for 3 hours. A few drops of N,N-dimethylformamide and methane sulfonyl chloride (0.003 mL, 0.032 mmol) were added and the reaction mixture was stirred at 23° C. for 1 hour. Additional methane sulfonyl chloride (0.006 mL, 0.064 mmol) was added and the reaction mixture was stirred at 23° C. for 72 hours. The reaction mixture was concentrated under reduced pressure. The concentrate was diluted with diethyl ether and 1 N hydrochloric acid was added until no further precipitation was observed. The precipitate was then washed with water followed by diethyl ether. The solid was dissolved in 1% triethylamine/dichloromethane and purified by preparative thin layer chromatography eluting with 5% (5% triethylamine/methanol)/dichloromethane. The silica gel was washed with 10% (5% triethylamine/methanol)/dichloromethane to give the triethylamine salt of the title compound (4.7 mg, 23%). 1H NMR (500 MHz, DMSO-d6) δ 1.16 (t, J=6.71 Hz, 9H) 2.94 (s, 3 H) 3.08 (bs, 6 H) 4.26 (d, 2 H) 5.40 (bs, 2 H) 7.06 (m, 2 H) 7.12 (d, J=8.54 Hz, 1 H) 7.23 (m, 5 H) 7.40 (t, J=7.32 Hz, 1 H) 7.50 (t, J=6.41 Hz, 1 H) 8.10 (d, J=6.10 Hz, 1 H).

Workup

  1. temperaturewarmed to 23° C.
  2. stirringstirred for 2.5 hours
  3. stirringthe mixture was stirred at 23° C. for 15 hours
  4. temperatureto increase solubility
  5. stirringthe reaction mixture was stirred at 23° C. for 3 hours
  6. stirringthe reaction mixture was stirred at 23° C. for 1 hour
  7. stirringthe reaction mixture was stirred at 23° C. for 72 hours
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additionThe concentrate was diluted with diethyl ether and 1 N hydrochloric acid
  10. additionwas added until no further precipitation
  11. washThe precipitate was then washed with water
  12. dissolutionThe solid was dissolved in 1% triethylamine/dichloromethane
  13. custompurified by preparative thin layer chromatography
  14. washeluting with 5% (5% triethylamine/methanol)/dichloromethane
  15. washThe silica gel was washed with 10% (5% triethylamine/methanol)/dichloromethane

Sources & evidence

ORD record
ord-527c23a1561e4c5d953c35c6f448d901
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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