Triethylamine → (S,E)-tert-butyl 3-(3-(2-(tert-butoxycarbonylamino)butanamido)prop-1-enyl)-1H-indole-1-carboxylate

HRID 1039026Notes

Reaction equation

HRID 1039026 reaction equation
[CH2:1]([NH:4][C:5](=[O:17])[C@@H:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][CH3:8])[CH:2]=[CH2:3].[C:18]([O:22][C:23]([N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27](Br)=[CH:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[C:12]([O:11][C:10]([NH:9][C@@H:6]([CH2:7][CH3:8])[C:5]([NH:4][CH2:1]/[CH:2]=[CH:3]/[C:27]1[C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:25]([C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:24])[CH:26]=1)=[O:17])=[O:16])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 20097636tert-Butyl 3-bromo-1H-indole-1-carboxylateHCID 86654756(S)-tert-butyl 1-(allylamino)-1-oxobutan-2-ylcarbamate

Product 1

HCID 67235756(S,E)-tert-butyl 3-(3-(2-(tert-butoxycarbonylamino)butanamido)prop-1-enyl)-1H-indole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A 50 mL sealed tube was charged with (S)-tert-butyl 1-(allylamino)-1-oxobutan-2-ylcarbamate (500 mg, 2.07 mmol), 3-bromo-indole-1-carboxylic acid tert-butyl ester (620 mg, 2.09 mmol), palladium (II) acetate (59 mg, 0.263 mmol), tri-o-tolylphosphine (180 mg, 0.591), acetonitrile (10 mL), and triethylamine (0.6 mL, 4.30 mmol). The tube was flushed with argon and sealed, then stirred and heated to 90° C. for 24 h. The resulting mixture was concentrated in vacuo and the resulting residue purified via flash silica gel chromatography (Analogix IF-280, SF65-150 g column, gradient 90:10-50:50 Heptane:EtOAc) to yield (S,E)-tert-butyl 3-(3-(2-(tert-butoxycarbonylamino)butanamido)prop-1-enyl)-1H-indole-1-carboxylate. 1H NMR (300 MHz, CDCl3) δ 7.58 (s, 1H), 7.23-7.36 (m, 4H), 6.60-6.66 (m, 1H), 6.20-6.51 (m, 1H), 4.05-4.11 (m, 1H), 3.86-3.91 (m, 2H), 1.83-1.93 (m, 1H), 1.59-1.72 (m, 1H), 1.44 (s, 18H), and 0.95 (t, J=7.4 Hz, 3H).

Workup

  1. customA 50 mL sealed tube
  2. customThe tube was flushed with argon
  3. customsealed
  4. concentrationThe resulting mixture was concentrated in vacuo
  5. customthe resulting residue purified via flash silica gel chromatography (Analogix IF-280

Sources & evidence

ORD record
ord-8665a62171d14407a061b056c7ffd46e
Source dataset
uspto-grants-2013_10
Patent number
US08552032B2

Reaction notes

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