Triethylamine → HCID 19028032, compound

HRID 2257130Notes

Reaction equation

HRID 2257130 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[C:12]([O:13][CH3:14])=[CH:11][C:10]([CH3:15])=[C:9]([O:16][CH3:17])[C:8]=2[O:18][CH3:19])[N:6]=1.C(OC(C[N:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH:29]1[C:37](O)=[O:38])=O)(C)(C)C.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.O>[CH3:19][O:18][C:8]1[C:9]([O:16][CH3:17])=[C:10]([CH3:15])[CH:11]=[C:12]([O:13][CH3:14])[C:7]=1[C:5]1[N:6]=[C:2]([NH:1][C:37]([C:29]2[NH:28][C:36]3[C:31]([CH:30]=2)=[CH:32][CH:33]=[CH:34][CH:35]=3)=[O:38])[S:3][CH:4]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 19028019HCID 19028019, compoundHCID 19028033HCID 19028033, compound

Product 1

HCID 19028032HCID 19028032, compoundYield 33.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

0.16 g of 2-amino-4-(2,3,6-trimethoxy-4-methylphenyl)thiazole is dissolved in 10 ml of DMF. 0.18 g of N-(tert-butyloxycarbonylmethyl)-2-indolinecarboxylic acid, 0.2 ml of triethylamine and 0.38 g of BOP are added, and the reaction mixture is left stirring for 48 hours. 100 ml of water are added, the resulting mixture is extracted with AcOEt, and the organic phase is separated after settling has taken place, dried over sodium sulphate and concentrated under vacuum. The residue is dissolved in 10 ml of CHCl3, 10 ml of TFA are then added and the reaction mixture is stirred at r.t. for 2 hours 30 minutes. It is concentrated under vacuum, adding three times 20 ml of benzene. The residue is dissolved in 20 ml of dimethoxyethane, 0.1 ml of triethylamine and 0.112 g of DDQ are then added and the reaction mixture is left overnight at room temperature. It is concentrated under vacuum, and the residue is taken up in AcOEt and washed successively with 1N NaOH solution, with KHSO4 solution and with sodium chloride solution; the organic phase is separated after settling has taken place, dried over sodium sulphate, filtered and concentrated under vacuum. The residue is chromatographed on silica gel, eluting with CHCl3 /AcOEt (50:50; v/v). The fractions of pure products are concentrated under vacuum, and the residue is solidified in pentane to yield 0.08 g of the expected product; m.p.=200° C.

Workup

  1. waitthe reaction mixture is left
  2. extractionthe resulting mixture is extracted with AcOEt
  3. customthe organic phase is separated after settling
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated under vacuum
  6. dissolutionThe residue is dissolved in 10 ml of CHCl3
  7. addition10 ml of TFA are then added
  8. stirringthe reaction mixture is stirred at r.t. for 2 hours 30 minutes
  9. concentrationIt is concentrated under vacuum
  10. additionadding three times 20 ml of benzene
  11. dissolutionThe residue is dissolved in 20 ml of dimethoxyethane
  12. addition0.1 ml of triethylamine and 0.112 g of DDQ are then added
  13. waitthe reaction mixture is left overnight at room temperature
  14. concentrationIt is concentrated under vacuum
  15. washwashed successively with 1N NaOH solution, with KHSO4 solution and with sodium chloride solution
  16. customthe organic phase is separated after settling
  17. dry with materialdried over sodium sulphate
  18. filtrationfiltered
  19. concentrationconcentrated under vacuum
  20. customThe residue is chromatographed on silica gel
  21. washeluting with CHCl3 /AcOEt (50:50; v/v)
  22. concentrationThe fractions of pure products are concentrated under vacuum

Sources & evidence

ORD record
ord-20ca3e2cdbf1490ab6f064d9c666ffd3
Source dataset
uspto-grants-1997_08
Patent number
US05656648

Reaction notes

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