Ammonia → HCID 23447961, compound

HRID 1840311Notes

Reaction equation

HRID 1840311 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:21]2[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C([N:32](CC)CC)C.[Cl:37]C(OCC(C)C)=O.N.C(Cl)[Cl:47]>C(Cl)Cl.C1COCC1>[ClH:37].[ClH:47].[N:11]1([CH:14]([C:21]2[CH:29]=[CH:28][C:24]([C:25]([NH2:32])=[O:27])=[CH:23][CH:22]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 6344DichloromethaneHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 10786928HCID 10786928, compound

Product 1

HCID 23447961HCID 23447961, compound

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Compound 78 (0.11 g, 0.28 mmol) was dissolved in dry methylene chloride/THF, 1:1 (5 mL) and cooled to −20° C. Triethylamine (78 μL, 0.56 mmol) was added and then i-butyl chloroformate (37 μL, 028 mmol). After 10 min, ammonia in methylene chloride (0.5 mL, 1.1M, 0.56 mmol) was added and the temperature was allowed to rise slowly to 25° C. After 3 h, the solvent was removed in vacuo and the residue was purified by chromatograpy on silica (CH2Cl2/MeOH/NH3, 95:5:1 and 90:10:1) to give 70 mg (62%). Treatment with HCl in methanol 3 h at 50° C., removal of solvent in vacuo and chromatograpy on silica (CH2Cl2MeOH/NH3, 90:10:1 and 80:20:1) gave the free amine which was converted to the dihydrochloride salt 82. Mp: 192-200° C. IR (KBr) (cm−1): 3939(br), 3184(br), 2700(br), 1665, 1610, 1565, 1426. MS (amine): 295, 250, 210, 165, 152. 1H NMR: (amine, CD3OD): δ=7.96-7.22 (m, 9H, Ar—H), 4.93 (s, 2H, NH), 4.40 (s, 1H, Ar2CH), 2.94+2.46 (2m, 8H, piperazine-H). Anal. calc. for C18H21N3O×2HCl×1.1H2O, C, 55.70; H,6.54; N, 10.83. Found C, 55.83; H, 6.76; N, 10.75.

Workup

  1. customto rise slowly to 25° C
  2. waitAfter 3 h
  3. customthe solvent was removed in vacuo
  4. customthe residue was purified by chromatograpy on silica (CH2Cl2/MeOH/NH3, 95:5:1 and 90:10:1)
  5. customto give 70 mg (62%)
  6. customTreatment with HCl in methanol 3 h at 50° C., removal of solvent in vacuo and chromatograpy on silica (CH2Cl2MeOH/NH3, 90:10:1 and 80:20:1)

Sources & evidence

ORD record
ord-6cc138e05eae4524b5ff63d398f8570e
Source dataset
uspto-grants-2004_01
Patent number
US06680321B1

Reaction notes

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