Diisopropylethylamine → HCID 44128566, compound

HRID 1970632Notes

Reaction equation

HRID 1970632 reaction equation
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[F:13][C:14]([F:19])([F:18])[CH2:15]CO.CCN(C(C)C)C(C)C.[O:29]=[C:30]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)[CH2:31][NH:32][C:33]([C:35]1[CH:39]=[C:38]([O:40][CH2:41][C:42]([N:44]2[CH2:48][CH2:47][CH2:46][C@H:45]2[C:49](=[O:55])[NH:50][CH:51]2[CH2:54][CH2:53][CH2:52]2)=[O:43])[N:37]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[N:36]=1)=[O:34]>ClCCl>[F:19][C:14]([F:13])([F:18])[CH2:15][CH2:7][O:6][C:5]([N:65]1[CH2:64][CH2:63][N:62]([C:30](=[O:29])[CH2:31][NH:32][C:33]([C:35]2[CH:39]=[C:38]([O:40][CH2:41][C:42]([N:44]3[CH2:48][CH2:47][CH2:46][C@H:45]3[C:49](=[O:55])[NH:50][CH:51]3[CH2:54][CH2:53][CH2:52]3)=[O:43])[N:37]([C:56]3[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=3)[N:36]=2)=[O:34])[CH2:67][CH2:66]1)=[O:11]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 1375123,3,3-Trifluoro-1-propanolHCID 66854863HCID 66854863, compound

Product 1

HCID 44128566HCID 44128566, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 22 mg triphosgene and 31 l 3,3,3-trifluoropropan-1-ol in 3 ml dichloromethane were added 37 l DIPEA dropwise at 0° C. After 2 h a solution of 93 mg 5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide and 37 l DIPEA in 1 ml dichloromethane were added at 0° C. The reaction mixture was allowed to warm to RT overnight. Excess triphosgene was destroyed by adding a solution of 140 mg NaOH in 5 ml water and stirring for 2 h. The layers were separated, the organic layer washed with 1 M HCl and dried over MgSO4 and concentrated. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give the title compound. Yield: 25 mg MS (ES+): m/e=678.

Workup

  1. customExcess triphosgene was destroyed
  2. additionby adding a solution of 140 mg NaOH in 5 ml water
  3. customThe layers were separated
  4. washthe organic layer washed with 1 M HCl
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative HPLC (
  8. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-06ca833869bf4b85a19df078a4314d3f
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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