1-Hydroxybenzotriazole → 3-Bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamide

HRID 1845180Notes

Reaction equation

HRID 1845180 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:10]=1)[C:5]([OH:7])=O.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:49][C:50]1[N:55]=[CH:54][C:53]([CH2:56][NH2:57])=[CH:52][N:51]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:10]=1)[C:5]([NH:57][CH2:56][C:53]1[CH:52]=[N:51][C:50]([CH3:49])=[N:55][CH:54]=1)=[O:7]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21294601(2-Methylpyrimidin-5-yl)methanamineHCID 581881193-Bromo-5-(pyrrolidine-1-carbonyl)benzoic acid

Product 1

HCID 581880073-Bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Into a round-bottom flask were charged 3-bromo-5-(pyrrolidine-1-carbonyl)benzoic acid (340 mg, 1.0 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.39 g, 2.0 mmol), 1-hydroxybenzotriazole (0.30 g, 2.2 mmol), N,N-diisopropylethylamine (0.2 g, 1.5 mmol), methylene chloride (10 mL), 4-dimethylaminopyridine (5 mg, 0.04 mmol), and (2-methylpyrimidin-5-yl)methanamine (240 mg, 1.5 mmol). The mixture was stirred at room temperature overnight, and then diluted with CH2Cl2. The separated organic phase was washed with aq. Na2HPO4, brine, and dried over Na2SO4, and concentrated. The residue was purified via flash chromatography to afford the desired product as an oil. LC-MS: 404.8 [M+1]+; 1H NMR (400 MHz, CDCl3): 8.68 (s, 2H), 7.95 (t, J=1.6 Hz, 1H), 7.76 (t, J=1.3 Hz, 1H), 7.74-7.71 (m, 1H), 7.61 (t, J=1.5 Hz, 1H), 4.57 (d, J=5.8 Hz, 2H), 3.56 (t, J=6.8 Hz, 2H), 3.37 (t, J=6.4 Hz, 2H), 2.73 (s, 3H), 1.96-1.89 (m, 4H).

Workup

  1. washThe separated organic phase was washed with aq. Na2HPO4, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified via flash chromatography

Sources & evidence

ORD record
ord-c26ae73c546e4f49bce656cff007db28
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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