1-Hydroxybenzotriazole → 3-[3-(1-tert-butoxycarbonylpyrrolidin-3-yloxy)benzamido]-4-methyl-N-(3-morpholinophenyl)benzamide

HRID 2415716Notes

Reaction equation

HRID 2415716 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH:22]([O:25][C:26]2[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=2)[C:29]([OH:31])=O)[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[NH2:35][C:36]1[CH:37]=[C:38]([CH:54]=[CH:55][C:56]=1[CH3:57])[C:39]([NH:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[CH:43]=1)=[O:40].ON1C2C=CC=CC=2N=N1>CN(C=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH:22]([O:25][C:26]2[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=2)[C:29]([NH:35][C:36]2[CH:37]=[C:38]([CH:54]=[CH:55][C:56]=2[CH3:57])[C:39]([NH:41][C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)[CH:43]=2)=[O:40])=[O:31])[CH2:21]1)=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222911363-{[1-(tert-Butoxycarbonyl)pyrrolidin-3-yl]oxy}benzoic acidHCID 226361453-amino-4-methyl-N-(3-morpholinophenyl)benzamide

Product 1

HCID 226361163-[3-(1-tert-butoxycarbonylpyrrolidin-3-yloxy)benzamido]-4-methyl-N-(3-morpholinophenyl)benzamideYield 51.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.23 g) was added to a stirred mixture of 3-(1-tert-butoxycarbonylpyrrolidin-3-yloxy)benzoic acid (0.307 g), 3-amino-4-methyl-N-(3-morpholinophenyl)benzamide (0.312 g), 1-hydroxybenztriazole (0.202 g) and DMF (5 ml) which had been cooled to 0° C. The resultant reaction mixture was stirred at ambient temperature for 40 hours. The mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and with a saturated aqueous sodium bicarbonate solution, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica gel using a 3:1 mixture of isohexane and ethyl acetate as eluent. There was thus obtained the title compound as a solid (0.31 g); NMR Spectrum: (DMSOd6) 1.38 (s, 9H), 2.12 (m, 2H), 2.27 (s, 3H), 3.08 (t, 4H), 3.37 (m, 3H), 3.57 (m, 1H), 3.74 (t, 4H), 5.05 (m, 1H), 6.67 (d, 1H), 7.17 (m, 2H), 7.3 (d, 1H), 7.42 (m, 3H), 7.52 (s, 1H), 7.57 (d, 1H), 7.78 (d, 1H), 7.93 (s, 1H), 10.0 (s, 1H), 10.01 (s, 1H); Mass Spectrum: M+H+ 601.

Workup

  1. customThe resultant reaction mixture
  2. customThe mixture was partitioned between ethyl acetate and water
  3. washThe organic phase was washed with water and with a saturated aqueous sodium bicarbonate solution
  4. dry with materialdried over magnesium sulphate
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica gel using
  7. additiona 3:1 mixture of isohexane and ethyl acetate as eluent

Sources & evidence

ORD record
ord-510d8265242e4014bbc0c44db4682c8b
Source dataset
uspto-grants-2004_11
Patent number
US06821965B1

Reaction notes

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