Dichloromethane → (+/-)-(3-Amino-propyl)-n-[1-(3-benzyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-propyl]-4-chloro-benzamide, hydrochloride salt

HRID 1795946Notes

Reaction equation

HRID 1795946 reaction equation
C(OC(=O)NCCC[NH:11][CH:12]([C:15]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19](=[O:28])[C:18]2=[CH:29][CH:30]=[CH:31][N:17]2[N:16]=1)[CH2:13][CH3:14])(C)(C)C.C([N:35]([CH2:38][CH3:39])CC)C.[Cl:40][C:41]1[CH:49]=[CH:48][C:44]([C:45](Cl)=[O:46])=[CH:43][CH:42]=1.[CH2:50](Cl)Cl>>[ClH:40].[NH2:35][CH2:38][CH2:39][CH2:50][C:48]1[CH:49]=[C:41]([Cl:40])[CH:42]=[CH:43][C:44]=1[C:45]([NH:11][CH:12]([C:15]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19](=[O:28])[C:18]2=[CH:29][CH:30]=[CH:31][N:17]2[N:16]=1)[CH2:13][CH3:14])=[O:46]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 85014-Chlorobenzoyl chlorideHCID 21025743{3-[1-(3-Benzyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-propylamino]-propyl}-carbamic acid tert-butyl ester

Product 1

HCID 131725695(+/-)-(3-Amino-propyl)-n-[1-(3-benzyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-propyl]-4-chloro-benzamide, hydrochloride saltYield 94%

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-{3-[1-(3-benzyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-propylamino]-propyl}-carbamic acid tert-butyl ester (610 mg, 1.39 mmole) in methylene chloride (10 mL) at 0° C. was added triethylamine (290 μL, 2.08 mmol) followed by 4-chlorobenzoyl chloride (265 mL, 2.08 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 crude product by flash column chromatography (SiO2, EtOAc/Hexane 4:1) gave the title compound as a white foam (755 mg, 94%): 1H NMR (CDCl3) δ 7.22 (m, 11H), 6.52 (m, 1H), 5.83 (m, 2H), 4.82 (d, 1H, J=16.0 Hz), 4.00 (m, 1H), 3.21 (m, 2H), 2.65 (m, 2H), 1.97 (m, 1H), 1.75 (m, 1H), 1.32 (s, 11H), 0.62 (t, 3H, J=6.84 Hz); 13C NMR (CDCl3) δ 171.8, 156.1, 155.6, 146.9, 137.0, 136.1, 135.0, 129.3, 129.2, 128.0, 127.2, 121.5, 118.4, 111.8, 109.7, 79.7, 54.9, 44.6, 42.5, 38.0, 31.9, 38.7, 24.7, 10.8; MS (ESI+) 578.31 (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 crude product by flash column chromatography (SiO2, EtOAc/Hexane 4:1)

Sources & evidence

ORD record
ord-7875ccd83bf243fabcc9ce166abcd689
Source dataset
uspto-grants-2006_04
Patent number
US07030118B2

Reaction notes

Loading…