Trifluoroacetic acid → HCID 59752668, compound

HRID 2106215Notes

Reaction equation

HRID 2106215 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:13]=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][CH:26]=3)[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.C(OC(N1CCC2N(CC3C=CC=CC=3)N=CC=2CC1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:18]([N:14]1[C:15]2[CH2:16][CH2:17][NH:8][CH2:9][CH2:10][C:11]=2[C:12]([C:25]2[CH:26]=[CH:27][C:28]([C:31]#[N:32])=[CH:29][CH:30]=2)=[N:13]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 67269264HCID 67269264, compoundHCID 67269550HCID 67269550, compound

Product 1

HCID 59752668HCID 59752668, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 43, Step C, 0.30 g) in 9 mL of 1,4-dioxane was added 0.20 g of K3PO4, 0.10 g of 4-cyanophenylboronic acid, and 0.05 g of PdCl2dppf. The mixture was heated at reflux for 72 h. The mixture was filtered through diatomaceous earth and concentrated in vacuo to give 0.33 g of an orange solid. Chromatography on SiO2 (5 to 30% EtOAc/hexanes) afforded 0.21 g of a 7:1 mixture of 1-benzyl-3-(4-cyano-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester and a side product, 1-benzyl-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The mixture of compounds (0.21 g) was dissolved in 7 mL CH2Cl2 and 7 mL of TFA was added. The mixture was stirred at RT for 1 h and concentrated in vacuo. The crude product was dissolved in CH2Cl2 and treated with Dowex® 550A resin. After stirring for 2 h, the mixture was filtered and concentrated in vacuo. Chromatography using a C18 reverse phase column afforded 0.14 g of the title compound as its TFA salt. MS (ESI): exact mass calculated for C21H20N4, 328.17; found, m/z 329.1 [M+H]+, 351.1 [M+Na]+. 1H NMR (500 MHz, CD3OD): 7.83-7.81 (m, 2H), 7.76-7.74 (m, 2H), 7.36-7.28 (m, 3H), 7.19-7.17 (m, 2H), 5.46 (s, 2H), 3.39-3.37 (m, 4H), 3.15-3.09 (m, 4H).

Workup

  1. customChromatography on SiO2 (5 to 30% EtOAc/hexanes) afforded
  2. concentrationconcentrated in vacuo
  3. dissolutionThe crude product was dissolved in CH2Cl2
  4. additiontreated with Dowex® 550A resin
  5. stirringAfter stirring for 2 h
  6. filtrationthe mixture was filtered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2ded14284a3a4f5ea087092d2b0281b1
Source dataset
uspto-grants-2009_08
Patent number
US07579470B2

Reaction notes

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