Hydrochloric Acid → (+/-)-N-(3-Amino-propyl)-N-(3-benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-ylmethyl)-4-chloro-benzamide, hydrochloride salt

HRID 1796003Notes

Reaction equation

HRID 1796003 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17](=[O:26])[C:16]2=[C:27]([Cl:30])[CH:28]=[CH:29][N:15]2[N:14]=1)(C)(C)C.CCN(CC)CC.[Cl:39][C:40]1[CH:48]=[CH:47][C:43]([C:44](Cl)=[O:45])=[CH:42][CH:41]=1.Cl>C(Cl)Cl.O1CCOCC1.C(#N)C.O>[ClH:30].[NH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:12][C:13]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17](=[O:26])[C:16]2=[C:27]([Cl:30])[CH:28]=[CH:29][N:15]2[N:14]=1)[C:44](=[O:45])[C:43]1[CH:47]=[CH:48][C:40]([Cl:39])=[CH:41][CH:42]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 85014-Chlorobenzoyl chlorideHCID 69591865(+/-)-{3-[(3-Benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-ylmethyl)-amino]-propyl}-carbamic acid tert-butyl ester

Product 1

HCID 131725701(+/-)-N-(3-Amino-propyl)-N-(3-benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-ylmethyl)-4-chloro-benzamide, hydrochloride saltYield 102.4%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-{3-[(3-benzyl-5-chloro-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-ylmethyl)-amino]-propyl}-carbamic acid tert-butyl ester (12 mg, 0.027 mmole) in methylene chloride (0.5 mL) at 0° C. was added Et3N (11 μL, 0.081 mmole) followed by 4-chlorobenzoyl chloride (10 mL, 0.081 mmol). After stirring at 0° C. for 1.5 h, the reaction was quenched with 10 mL of saturated NaHCO3 solution and extracted with EtOAc (3×20 mL). The pooled organic extracts were dried over anhydrous MgSO4 and concentrated in vacuo. Purification of the residue by flash column chromatography (SiO2, 2% MeOH/CHCl3) gave a residue which was immediately treated with 4 N HCl in dioxane (1 mL). The crude product was lyophilized with acetonitrile/water to give the title compound as a white powder (7.2 mg, 51%): MS (ESI+) 484 (M++H).

Workup

  1. customthe reaction was quenched with 10 mL of saturated NaHCO3 solution
  2. extractionextracted with EtOAc (3×20 mL)
  3. dry with materialThe pooled organic extracts were dried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by flash column chromatography (SiO2, 2% MeOH/CHCl3)
  6. customgave a residue which

Sources & evidence

ORD record
ord-e71a63e325254b0eab1a61cd903161bf
Source dataset
uspto-grants-2006_04
Patent number
US07030118B2

Reaction notes

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