Triethylamine → HCID 66888934, compound

HRID 1911235Notes

Reaction equation

HRID 1911235 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=1)[C:12]([C:25]([OH:27])=O)=[CH:11]2.C(N(CC)CC)C.[CH3:35][C:36]([CH3:52])([CH3:51])[C:37]([O:39][CH2:40][C:41]1[S:42][C:43]2[C:48]([N:49]=1)=[CH:47][C:46]([NH2:50])=[CH:45][N:44]=2)=[O:38]>ClCCl.CN(C)C=O.O1CCCC1>[CH3:35][C:36]([CH3:52])([CH3:51])[C:37]([O:39][CH2:40][C:41]1[S:42][C:43]2[C:48]([N:49]=1)=[CH:47][C:46]([NH:50][C:25]([C:12]1[N:13]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[C:14]3[C:10]([CH:11]=1)=[CH:9][C:8]([F:7])=[CH:16][CH:15]=3)=[O:27])=[CH:45][N:44]=2)=[O:38]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chloride2×HCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acidHCID 58125487(6-Aminothiazolo[5,4-b]pyridin-2-yl)methyl pivalate

Product 1

HCID 66888934HCID 66888934, compoundYield 20.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

240 microlitres (2.78 mmol) of oxalyl chloride are added, dropwise at 0° C., to a solution of 0.4 g (1.39 mmol) of 5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, prepared in step 1.1, in 10 mL of dichloromethane and 0.5 mL of dimethylformamide. The mixture is stirred for 15 minutes at 0° C. and then for 1 hour at 20° C. After this time, a further 120 microlitres (1.39 mmol) of oxalyl chloride are added and stirring is continued for 30 minutes at 20° C. The reaction mixture is then concentrated under reduced pressure and taken up in 5 mL of tetrahydrofuran. 219 microlitres of triethylamine and then a solution of 0.44 g (1.67 mmol) of (6-amino-thiazolo[5,4-b]pyrid-2-yl)methyl 2,2-dimethylpropanoate, prepared in step 4.2, in 10 mL of tetrahydrofuran are added, under an inert atmosphere. The reaction mixture is stirred for 15 hours at 20° C. and for 1 hour at 40° C., and then concentrated under reduced pressure and taken up in 100 mL of water. The aqueous phase is extracted three times with 50 mL of ethyl acetate. The organic phases are combined, washed successively with 50 mL of saturated sodium hydrogen carbonate solution and with 50 mL of saturated sodium chloride solution, and then dried over sodium sulfate and concentrated under reduced pressure. The product thus obtained is purified on a column of alumina, eluting with dichloromethane. 0.15 g of the expected product is thus isolated.

Workup

  1. waitfor 1 hour at 20° C
  2. stirringstirring
  3. waitis continued for 30 minutes at 20° C
  4. concentrationThe reaction mixture is then concentrated under reduced pressure
  5. additionare added, under an inert atmosphere
  6. stirringThe reaction mixture is stirred for 15 hours at 20° C. and for 1 hour at 40° C.
  7. concentrationconcentrated under reduced pressure
  8. extractionThe aqueous phase is extracted three times with 50 mL of ethyl acetate
  9. washwashed successively with 50 mL of saturated sodium hydrogen carbonate solution and with 50 mL of saturated sodium chloride solution
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe product thus obtained
  13. customis purified on a column of alumina
  14. washeluting with dichloromethane

Sources & evidence

ORD record
ord-3793cac833c840a893296212a7c41626
Source dataset
uspto-grants-2013_12
Patent number
US08604050B2

Reaction notes

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