Hydrochloric Acid → HCID 178492641, compound

HRID 420120Notes

Reaction equation

HRID 420120 reaction equation
[CH:1]1([C:4]2[N:8]3[CH:9]=[C:10]([C:15]([O:17]C)=O)[CH:11]=[C:12]([O:13][CH3:14])[C:7]3=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[OH-].[Na+].Cl.Cl.[NH:23]1[C:27]([C:28]2[CH:29]=[C:30]3[C:40](=[CH:41][CH:42]=2)[O:39][C:33]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:32][C:31]3=[O:43])=[N:26][N:25]=[N:24]1.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C1COCC1.CO.O>[CH:1]1([C:4]2[N:8]3[CH:9]=[C:10]([C:15]([N:36]4[CH2:37][CH2:38][C:33]5([CH2:32][C:31](=[O:43])[C:30]6[C:40](=[CH:41][CH:42]=[C:28]([C:27]7[NH:26][N:25]=[N:24][N:23]=7)[CH:29]=6)[O:39]5)[CH2:34][CH2:35]4)=[O:17])[CH:11]=[C:12]([O:13][CH3:14])[C:7]3=[N:6][CH:5]=2)[CH2:2][CH2:3]1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66649343Methyl 3-cyclopropyl-8-methoxyimidazo[1,2-a]pyridin-6-carboxylateHCID 178479612HCID 178479612, compound

Product 1

HCID 178492641HCID 178492641, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 3-cyclopropyl-8-methoxyimidazo[1,2-a]pyridin-6-carboxylate (30 mg, 0.122 mmol) was dissolved in THF (1.5 mL) and MeOH (1.5 mL), and added by aqueous 5 N sodium hydroxide solution (0.12 mL, 0.609 mmol), then stirred at 60° C. for 2 hours. This was cooled to room temperature, added by 5 N hydrochloric acid (0.12 mL, 0.609 mL), concentrated under reduced pressure, and then azeotroped with toluene. The residue was dissolved in DMF (2 mL) and water (0.5 mL), and 6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one hydrochloride (47 mg, 0.146 mmol), triethylamine (0.026 mL, 0.183 mmol), HOBT (25 mg, 0.183 mmol) and EDCI HCl (35 mg, 0.183 mol) were added thereto. The reaction mixture was stirred at 90° C. for 2 hours, then cooled to room temperature, and water was added thereto. The precipitated solid was collected by filtration, and dried under reduced pressure to obtain the intended compound as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.42 (1H, s), 8.24 (1H, d, J=8.5 Hz), 8.19 (1H, s), 7.33 (1H, d, J=8.5 Hz), 7.30 (1H, s), 6.68 (1H, s), 4.50-3.20 (5H, m), 3.95 (3H, s), 2.98 (2H, s), 2.10-1.80 (4H, m), 1.03-0.96 (2H, m), 0.69-0.64 (2H, m); MS [M+H]+=500.

Workup

  1. temperatureThis was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customazeotroped with toluene
  4. dissolutionThe residue was dissolved in DMF (2 mL)
  5. stirringThe reaction mixture was stirred at 90° C. for 2 hours
  6. temperaturecooled to room temperature
  7. filtrationThe precipitated solid was collected by filtration
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-2913cec8218a417f94791046b6a3b1d9
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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