Hydrochloric Acid → 2-Hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-(tetrahydrofuran-2-ylmethyl)-1H-indole-5-carboxamide hydrochloride

HRID 2245562Notes

Reaction equation

HRID 2245562 reaction equation
[OH:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][N:12]=1)=[CH:8][C:7]([C:24](OC)=[O:25])=[CH:6][CH:5]=2.[CH2:28]([NH2:34])[CH:29]1[O:33][CH2:32][CH2:31][CH2:30]1.C([O-])(O)=O.[Na+].[ClH:40]>>[ClH:40].[OH:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][N:12]=1)=[CH:8][C:7]([C:24]([NH:34][CH2:28][CH:29]1[CH2:30][CH2:31][CH2:32][O:33]1)=[O:25])=[CH:6][CH:5]=2

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 253298TetrahydrofurfurylamineHCID 516892Sodium BicarbonateHCID 136380045Methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate

Product 1

HCID 1354316582-Hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-N-(tetrahydrofuran-2-ylmethyl)-1H-indole-5-carboxamide hydrochlorideYield 27%

Procedure

Starting materials: methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate and tetrahydrofurfurylamine, but heated at reflux for 2 h. The cooled mixture was poured into a saturated NaHCO3 solution and concentrated in vacuo. The residue was suspended in methanol/dichloromethane, (1:1), silica gel (˜2 g) was added and the mixture was re-concentrated in vacuo. The resulting residue was purified on a silica gel column using dichloromethane/methanol, (100:1 to 25:2 and 1% ammonia solution in water (25%)), as the eluent to give the base. Yield: 27%: 1H NMR (DMSO-d6, 300 MHz) δ 14.75 (br s, 1H), 11.37 (br s, 1H), 10.69 (s, 1H), 8.50 (t, J=5.51 Hz, 1H), 8.22 (s, 1H), 8.06 (d, J=9.2 Hz, 1H), 7.99 (s, 1H), 7.82 (d, J=9.2 Hz, 1H), 7.54 (d, J=8.1 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 4.25 (s, 2H), 4.02-3.60 (m, 6H), 3.44-3.22 (m, 4H), 3.20-3.03 (m, 2H), 1.95-1.78 (m, 4H), 1.70-1.55 (m, 1H); MS (ES) m/z 437 (M++1). The base was transferred to the hydrochloride.

Workup

  1. temperatureat reflux for 2 h
  2. concentrationconcentrated in vacuo
  3. additionwas added
  4. concentrationthe mixture was re-concentrated in vacuo
  5. customThe resulting residue was purified on a silica gel column
  6. customto give the base

Sources & evidence

ORD record
ord-18eb80af57254678914fdb4381a45944
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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