Triethylamine → HCID 178448499, compound

HRID 1526995Notes

Reaction equation

HRID 1526995 reaction equation
[CH:1]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]([OH:16])=O)=[C:6]1[CH3:17])([CH2:3][CH3:4])[CH3:2].C1C=C2N=NN(O)C2=CC=1.N.C(N(CC)CC)C.[NH2:36][CH2:37][C:38]1[C:39]([OH:46])=[N:40][C:41]([CH3:45])=[CH:42][C:43]=1[CH3:44]>ClCCl>[CH:1]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]([NH:36][CH2:37][C:38]2[C:39]([OH:46])=[N:40][C:41]([CH3:45])=[CH:42][C:43]=2[CH3:44])=[O:16])=[C:6]1[CH3:17])([CH2:3][CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1131751H-Benzotriazol-1-ol--ammonia (1/1)HCID 117779067HCID 117779067, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178448499HCID 178448499, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-sec-butyl-2-methyl-1H-indole-3-carboxylic acid (97 mg, 0.42 mmol), 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (121 mg, 0.63 mmol), N-hydroxybenzotrizole (85 mg, 0.63 mmol) and triethylamine (127.26 mg, 1.26 mmol) in dichloromethane (30 mL) was stirred for 30 minutes at room temperature. Then to the mixture, 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (63.8 mg, 0.42 mmol) was added. The resulting mixture was stirred at room temperature for 12 hours. Then the mixture was washed with water (20 mL×3). The organic layer was concentrated to give a residue which was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give 1-sec-butyl-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-methyl-1H-indole-3-carboxamide (57 mg, 30%). LRMS (M+H+) m/z: calcd 365.2. found 365. HPLC purity (214 nm): 99%. 1H.NMR (300 MHz, CD3OD): δ 7.72-7.69 (m, 1H), 7.53 (d, J=7.2 Hz, 1H), 7.11-7.06 (m, 2H), 6.10 (s, 1H), 4.53-4.51 (m, 3H), 2.62 (s, 3H), 2.41 (s, 3H), 2.24 (s, 3H), 1.95-1.93 (m, 2H), 1.59 (d, J=6.9 Hz, 3H), 0.72 (t, J=7.5 Hz, 3H).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 12 hours
  2. washThen the mixture was washed with water (20 mL×3)
  3. concentrationThe organic layer was concentrated
  4. customto give a residue which
  5. customwas purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-842a786625944f1c8df344346dba3e5c
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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