Trifluoroacetic acid → HCID 11203422, compound

HRID 2250877Notes

Reaction equation

HRID 2250877 reaction equation
C(OC(N1CCC(N(C2C=C3C(CCN3C(=O)C)=CC=2)C(=O)/[CH:16]=[CH:17]/[C:18]2[CH:23]=[CH:22][C:21](Cl)=[CH:20][CH:19]=2)CC1)=O)(C)(C)C.ClC1C=CC(/C=C/C(O)=O)=CC=1.C(N1C2C(=CC=C(N(C3CCN(CCCC4C=CC=CC=4)CC3)C(=O)/C=C/C3C=CC=CC=3)C=2)CC1)(=O)C.[C:88]([N:91]1[C:99]2[C:94](=[CH:95][CH:96]=[C:97]([N:100]([CH:112]3[CH2:117][CH2:116][NH:115][CH2:114][CH2:113]3)[C:101](=[O:111])/[CH:102]=[CH:103]/[C:104]3[CH:109]=[CH:108][C:107]([Cl:110])=[CH:106][CH:105]=3)[CH:98]=2)[CH2:93][CH2:92]1)(=[O:90])[CH3:89].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:88]([N:91]1[C:99]2[C:94](=[CH:95][CH:96]=[C:97]([N:100]([CH:112]3[CH2:117][CH2:116][N:115]([CH2:16][CH2:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)[CH2:114][CH2:113]3)[C:101](=[O:111])/[CH:102]=[CH:103]/[C:104]3[CH:109]=[CH:108][C:107]([Cl:110])=[CH:106][CH:105]=3)[CH:98]=2)[CH2:93][CH2:92]1)(=[O:90])[CH3:89]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 6377974-Chlorocinnamic acidHCID 11477689HCID 11477689, compoundHCID 69209392HCID 69209392, compoundHCID 69213090HCID 69213090, compound

Product 1

HCID 11203422HCID 11203422, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

trans-4-{(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-[3-(4-chloro-phenyl)-acryloyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester. The ester (1.26 g, 87%) was prepared as in Example 20 using trans-3-(4-chloro-phenyl)-acrylic acid in place of trans-3-thiophen-3-yl-acrylic acid and 4-(1-acetyl-2,3-dihydro-1H-indol-6-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (Example 41, Step A) in place of 1-[6-(1-benzyl-piperidin-4-ylamino)-2,3-dihydro-indol-1-yl]-ethanone. 1H NMR (500 MHz, CDCl3): 8.02 (s, 1H), 7.56 (d, J=15.5 Hz, 1H), 7.21-7.17 (m, 5H), 6.73-6.71 (m, 1H), 6.10 (d, J=15.5 Hz, 1H), 4.84-4.79 (m, 1H), 4.17-4.12 (m, 4H), 3.29-3.24 (m, 2H), 2.80 (br s, 2H), 2.23 (s, 3H), 1.90-1.77 (m, 2H), 1.51-1.27 (m, 11H). MS: exact mass calculated for C29H34ClN3O4, 523.22; m/z found, 546.2 [M+Na]+, 548.2 [M+Na]+. Step B. trans-N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-3-(4-chloro-phenyl)-N-piperidin-4-yl-acrylamide. The intermediate from Step A (1.22 g, 2.32 mmol) was dissolved in CH2Cl2 (10 mL) and was treated with TFA (10 mL). The mixture was stirred for 30 min at rt and then was concentrated in vacuo. The residue was dissolved in CH2Cl2 and treated with Dowex 550A resin. After stirring for several hours, the mixture was filtered and concentrated in vacuo to give 966 mg (98%) of the desired compound, which was taken on to the next step without further purification. Step C. The title compound (54 mg, 61%) was prepared from the intermediate from Step B (70.0 mg, 0.165 mmol) as in Example 43, using 1,2-dichloroethane as the solvent. 1H NMR (500 MHz, CDCl3): 8.04 (s, 1H), 7.57 (d, J=15.5 Hz, 1H), 7.30-7.16 (m, 5H), 6.75 (br s, 1H), 6.14 (d, J=15.5 Hz, 1H), 4.75 (br s, 1H), 4.17-4.14 (m, 2H) 3.53-3.27 (m, 4H), 2.92 (br s, 2H), 2.28-2.23 (m, 4H), 2.07-2.04 (m, 2H), 1.66-1.43 (m, 9H), 1.29-1.11 (m, 5H), 0.89-0.86 (m, 2H). MS: exact mass calculated for C32H40ClN3O2, 533.28; m/z found, 534.2 [M+H]+, 556.3 [M+Na]+.

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. additiontreated with Dowex 550A resin
  4. stirringAfter stirring for several hours
  5. filtrationthe mixture was filtered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1f981b079b9d423cb821ed2ec9ff5b8f
Source dataset
uspto-grants-2008_01
Patent number
US07317025B2

Reaction notes

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