Trifluoroacetic anhydride → HCID 71288927, compound

HRID 246146Notes

Reaction equation

HRID 246146 reaction equation
[C:1]([C@H:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:14]=2)=[O:12])[CH2:5]1)(=O)[NH2:2].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1>[C:1]([C@H:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:14]=2)=[O:12])[CH2:5]1)#[N:2]

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 71287916HCID 71287916, compound

Product 1

HCID 71288927HCID 71288927, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

In a 25 mL pear-shaped flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-carbamoyl-cyclohexyl)-amide (72 mg, 0.124 mmol) was combined with pyridine (412 μl) to give a off-white solution. The reaction mixture was cooled at 0° C. and trifluoroacetic anhydride (0.71 M in pyridine, 26 μl, 0.18 mmol) was added dropwise. The reaction mixture was allowed to stir at room temperature for 30 min and then concentrated. The residue was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0-50% EtOAc) to afford 27 mg (39%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-cyano-cyclohexyl)-amide as a white solid. 1H NMR (300 MHz, DMSO-d6) δ: 9.14 (s, 1H), 8.66 (s, 1H), 8.40 (d, J=8.7 Hz, 1H), 8.06 (d, J=7.9 Hz, 1H), 8.01 (d, J=1.0 Hz, 1H), 7.38 (dd, J=8.7, 1.0 Hz, 1H), 5.73 (s, 2H), 4.18 (s, 3H), 4.09-4.28 (m, 1H), 3.59 (t, J=7.9 Hz, 2H), 3.41-3.60 (br. s., 1H), 2.24 (app. d, J=12.5 Hz, 1H), 2.07 (app. d, J=12.1 Hz, 1H), 1.59-1.91 (m, 5H), 1.39-1.59 (m, 1H), 0.86 (t, J=7.9 Hz, 2H), −0.08 (s, 9H).

Workup

  1. customto give a off-white solution
  2. concentrationconcentrated
  3. customThe residue was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0-50% EtOAc)

Sources & evidence

ORD record
ord-3f51666631bf4e12a40cd8100ffc6bbb
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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