Hydrochloric Acid → HCID 58997230, compound

HRID 251192Notes

Reaction equation

HRID 251192 reaction equation
[ClH:1].[NH2:2][OH:3].[OH-].[K+].[CH3:6][O:7][C:8](=[O:32])[CH2:9][N:10]1[CH2:13][CH:12]([CH2:14][N:15]([CH2:24][C:25]2[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=2)[CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:11]1.[ClH:33]>CO>[CH2:6]([Cl:33])[Cl:1].[CH3:6][OH:7].[NH4+:10].[OH-:3].[CH3:23][C:22]1[C:17]([CH2:16][N:15]([CH2:14][CH:12]2[CH2:13][N:10]([CH2:9][C:8]([NH:2][OH:3])=[O:32])[CH2:11]2)[CH2:24][C:25]2[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=2)=[N:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 67272987HCID 67272987, compound

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 58997230HCID 58997230, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
60 °C

Procedure

Hydroxylamine hydrochloride (1.0 g, 14.3 mmol) was dissolved in MeOH (6 mL) with slight heating. In a separate flask, KOH (1.36 g, 21.3 mmol) was dissolved in MeOH (6 mL) with heating to 60° C., then this was added to the above solution at 40° C. KCl precipitated out, and was cooled to 0° C. The clear portion of this suspension (3.2 mL) was added to (3-{[bis-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-azetidin-1-yl)-acetic acid methyl ester (0.1411 g, 0.38 mmol) and stirred at room temperature for 24 hours. 1N HCl (3 mL) was added until neutral, and extracted with CH2Cl2 (3×40 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by column chromatography on silica gel (25:1:1 then 10:1:1 CH2Cl2-MeOH—NH4OH) provided 67.3 mg (48%) of COMPOUND 346 as a white solid. 1H NMR (CDCl3) δ 2.07 (s, 6H), 2.57-2.73 (m, 5H), 3.03 (s, 2H), 3.32 (t, 2H, J=6.0 Hz), 3.69 (s, 4H), 7.09-7.13 (m, 2H), 7.40 (d, 2H, J=7.5 Hz), 8.36 (d, 2H, J=3.9 Hz). 13C NMR (CDCl3) δ 18.23, 29.15, 58.56, 59.63, 60.28, 60.69, 123.06, 133.80, 138.65, 146.22, 156.94, 167.02. ES-MS m/z 370.5 (M+H). Anal. Calcd. for C20H27N5O2.0.6CH4O.0.5H2O: C, 62.21; H, 7.70; N, 17.61. Found: C, 62.06; H, 7.61; N, 17.49.

Workup

  1. additionthis was added to the above solution at 40° C
  2. customKCl precipitated out
  3. temperaturewas cooled to 0° C
  4. extractionextracted with CH2Cl2 (3×40 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude material by column chromatography on silica gel (25:1:1

Sources & evidence

ORD record
ord-95932acb4c934267aaa4ed5a094c54a2
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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