Triethylamine → HCID 46222159, compound

HRID 1641034Notes

Reaction equation

HRID 1641034 reaction equation
C(N1C2C(=CC=CC=2)C=C1)(C)C.[CH:13]([N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25](=[O:29])[C:26]([Cl:28])=[O:27])=[CH:17]1)([CH3:15])[CH3:14].[NH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][CH2:40][OH:41])[CH2:35][CH2:34]1.C(N(CC)CC)C>C(Cl)Cl>[ClH:28].[OH:41][CH2:40][CH2:39][CH:36]1[CH2:37][CH2:38][N:33]([CH2:32][CH2:31][NH:30][C:26](=[O:27])[C:25]([C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:16]([CH:13]([CH3:15])[CH3:14])[CH:17]=2)=[O:29])[CH2:34][CH2:35]1.[OH:41][CH2:40][CH2:39][CH:36]1[CH2:37][CH2:38][N:33]([CH2:32][CH2:31][NH:30][C:26](=[O:27])[C:25]([C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:16]([CH:13]([CH3:15])[CH3:14])[CH:17]=2)=[O:29])[CH2:34][CH2:35]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4389257HCID 4389257, compoundHCID 19104155HCID 19104155, compoundHCID 59438561HCID 59438561, compound

Product 2

HCID 46222159HCID 46222159, compoundHCID 66739439HCID 66739439, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared according to general procedure B described in Scheme 1. N-Isopropylindole (150 mg, 0.94 mmol) was converted to 2-(1-isopropyl-1H-indol-3-yl)-2-oxoacetyl chloride as described in example 1 and treated with a solution of 2-(1-(2-aminoethyl)piperidin-4-yl)ethanol (236 mg, 1.13 mmol), triethylamine (1.3 mL, 9.4 mmol) in DCM (2 mL) and stirred at RT for 14 h. The reaction mixture was then washed with sat. NaHCO3 (1×3 mL), H2O (1×3 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by silica chromatography (Biotage, 10-50% MeOH/DCM, 30 min.) to provide N-(2-(4-(2-hydroxyethyl)piperidin-1-yl)ethyl)-2-(1-isopropyl-1H-indol-3-yl)-2-oxoacetamide and further purified using reverse phase HPLC. The purified material was converted to the HCl salt to afford (27 mg, 7% yield): 1H NMR (400 MHz, CDCl3): δ 9.11 (s, 1H), 8.45 (m, 1H), 7.93 (t, 1H), 7.44 (m, 1H), 7.34 (m, 2H), 4.71 (m, 1H), 3.71 (t, 2H), 3.47 (q, 2H), 2.92 (d, 2H) 2.55 (t, 2H), 2.01 (t, 2H), 1.70 (d, 2H), 1.62 (d, 6H), 1.53 (q, 3H), 1.33 (t, 3H); MS (ESI) m/z: Calculated for C22H31N3O3: 385.2. Found: 385.5 (M+H)+.

Workup

  1. washThe reaction mixture was then washed with sat. NaHCO3 (1×3 mL), H2O (1×3 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by silica chromatography (Biotage, 10-50% MeOH/DCM, 30 min.)

Sources & evidence

ORD record
ord-8c27f7f5146243b285d124ed055665e2
Source dataset
uspto-grants-2012_02
Patent number
US08114894B2

Reaction notes

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