Trifluoroacetic acid → HCID 24829866, compound

HRID 1435130Notes

Reaction equation

HRID 1435130 reaction equation
[NH2:1][C:2]([C:4]1[S:5][C:6]([N:32]2[C:36]3[CH:37]=[CH:38][C:39]([C:41]4[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=4)=[CH:40][C:35]=3[N:34]=[CH:33]2)=[CH:7][C:8]=1[O:9][CH:10]([C:12]1[CH:13]=[C:14]([O:18][CH:19]2[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]2)[CH:15]=[CH:16][CH:17]=1)[CH3:11])=[O:3].C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl>[CH3:46][N:44]1[CH:45]=[C:41]([C:39]2[CH:38]=[CH:37][C:36]3[N:32]([C:6]4[S:5][C:4]([C:2]([NH2:1])=[O:3])=[C:8]([O:9][CH:10]([C:12]5[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH:19]6[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]6)[CH:13]=5)[CH3:11])[CH:7]=4)[CH:33]=[N:34][C:35]=3[CH:40]=2)[CH:42]=[N:43]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 57937525HCID 57937525, compound

Product 1

HCID 24829866HCID 24829866, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(+/−)-1,1-Dimethylethyl 4-({3-[1-({2-(aminocarbonyl)-5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]-3-thienyl}oxy)ethyl]phenyl}oxy)-1-piperidinecarboxylate (0.378 g, 0.588 mmol) was dissolved in 12 mL of DCM with stirring and cooled to 0° C. TFA (3.0 mL, 39 mmol) was added, and the reaction was stirred for 1.5 h. The reaction was pipeted onto 80 mL of aqueous 2N NaOH solution, rinsing with DCM. The mixture was extracted three times with 4:1 DCM/i-PrOH. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded 0.218 g (68%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 8.17 (s, 1H), 7.93 (m, 1H), 7.90 (s, 1H), 7.75 (br s, 1H), 7.55 (dd, J=8.4, 1.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.42 (s, 1H), 7.26 (dd, J=8.1, 7.9 Hz, 1H), 7.11-7.06 (m, 2H), 7.04 (d, J=7.9 Hz, 1H), 6.84 (dd, J=8.1, 2.2 Hz, 1H), 5.69 (q, J=6.4 Hz, 1H), 4.34 (m, 1H), 3.84 (s, 3H), 2.90-2.81 (m, 2H), 2.53-2.43 (m, 2H), 1.88-1.76 (m, 2H), 1.67 (d, J=6.4 Hz, 3H), 1.42-1.26 (m, 2H). MS (APCI): 543 [M+H]+.

Workup

  1. stirringthe reaction was stirred for 1.5 h
  2. washrinsing with DCM
  3. extractionThe mixture was extracted three times with 4:1 DCM/i-PrOH
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-b2931831d1414e7987f13ae3ab68f5aa
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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