Trifluoroacetic acid → HCID 66604678, compound

HRID 2410872Notes

Reaction equation

HRID 2410872 reaction equation
[C:1]([C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:13]=3)[C:8]=2[CH:7]=[C:6]([CH:25]2[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]2)[CH:5]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCCl>[N:19]1([C:17]([C:12]2[CH:13]=[C:14]3[C:9]([C:8]4[CH:7]=[C:6]([CH:25]5[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]5)[CH:5]=[C:4]([C:1]([NH2:2])=[O:3])[C:16]=4[NH:15]3)=[CH:10][CH:11]=2)=[O:18])[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66604497HCID 66604497, compound

Product 1

HCID 66604678HCID 66604678, compoundYield 54.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

tert-Butyl 4-(1-carbamoyl-7-(morpholine-4-carbonyl)-9H-carbazol-3-yl)piperidine-1-carboxylate (Example 393, 50 mg, 0.099 mmol) was dissolved in 1,2-Dichloroethane (3 ml) and trifluoroacetic acid (1 ml, 12.98 mmol) and stirred for 1 hour at room temperature. Evaporation of volatiles and purification by reversed phase preparative HPLC, followed by filtration of product containing fractions through a PHENOMENEX® Strata-X cartridge (2 g adsorbent), a wash with Methanol, and elution with 2M NH3 in MeOH gave 21.9 mg 7-(morpholine-4-carbonyl)-3-(piperidin-4-yl)-9H-carbazole-1-carboxamide. MS (ESI) m/e−=405 and m/e=407 consistent with [M−H]− and [M+H]+. HPLC retention time 7.61 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA). 1H NMR (CD3OD) δ ppm 8.21 (s, 1H), 8.20 (d, 1H, J=8.0), 7.87 (d, 1H, J=1.5), 7.69 (s, 1H), 7.27 (dd, 1H, J=8.0, 1.5), 3.90-3.50 (b, 8H), 3.23 (br. d., 2H, J˜12), 2.91 (m, 1H), 2.83 (m, 2H), 1.97 (br. d., 2H, J˜12), 1.85 (m, 2H).

Workup

  1. customEvaporation of volatiles and purification by reversed phase preparative HPLC
  2. filtrationfollowed by filtration of product
  3. additioncontaining fractions through a PHENOMENEX® Strata-X cartridge (2 g adsorbent)
  4. washa wash with Methanol, and elution with 2M NH3 in MeOH

Sources & evidence

ORD record
ord-bf02e98b00704f8993ccb6cd7ff336b7
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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