Trifluoroacetic acid → 4-(2-Amino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

HRID 2075776Notes

Reaction equation

HRID 2075776 reaction equation
C(OC(=O)[NH:7][CH:8]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH:12]1[C:17](=[O:41])[NH:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]#[C:26][C:27]2[C:28]([C:33]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=3[OH:40])=[N:29][N:30]([CH3:32])[CH:31]=2)=[CH:21][CH:20]=1)=[O:10])(C)(C)C.C(O)(C(F)(F)F)=O>>[Cl:39][C:37]1[CH:36]=[CH:35][C:34]([OH:40])=[C:33]([C:28]2[C:27]([C:26]#[C:25][C:22]3[CH:23]=[CH:24][C:19]([NH:18][C:17]([CH:12]4[CH2:13][O:14][CH2:15][CH2:16][N:11]4[C:9](=[O:10])[CH:8]([NH2:7])[C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[O:41])=[CH:20][CH:21]=3)=[CH:31][N:30]([CH3:32])[N:29]=2)[CH:38]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136346688[2-(3-{4-[3-(5-Chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-morpholin-4-yl)-2-oxo-1-phenyl-ethyl]-carbamic acid tert-butyl ester2×

Product 1

HCID 1363466894-(2-Amino-2-phenyl-acetyl)-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amideYield 85%

Procedure

To a solution of compound 8D was slowly added TFA (20 eq). The reaction mixture was stirred at rt till all the compound 8D was reacted (4-5 h, checked with LCMS). The solvent was removed with rotavapor at 25° C. More dichloromethane was added and the solvent was removed again. The same process repeated two more times. The residua were then transferred to a separatory funnel with EtOAc and washed with saturated aqueous NaHCO3. It was dried over sodium sulfate and filtered. Solvent was removed to give the title compound 9D in >85% yield. It was used for next step without further purification. LCMS (ESI) m/z 592.34 (MNa+), 570.44 (MH+). HPLC: tR=4.27 min.

Workup

  1. customwas reacted (4-5 h, checked with LCMS)
  2. customThe solvent was removed with rotavapor at 25° C
  3. additionMore dichloromethane was added
  4. customthe solvent was removed again
  5. customThe residua were then transferred to a separatory funnel with EtOAc
  6. washwashed with saturated aqueous NaHCO3
  7. dry with materialIt was dried over sodium sulfate
  8. filtrationfiltered
  9. customSolvent was removed

Sources & evidence

ORD record
ord-c614a417821a4915b964ef9f752a37d7
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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