Pyridine → Methyl 2-(4-(propylcarbamoyl)phenylcarbamoyl)isoindoline-5-carboxylate

HRID 624112Notes

Reaction equation

HRID 624112 reaction equation
[NH2:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([NH:8][CH2:9][CH2:10][CH3:11])=[O:7])=[CH:4][CH:3]=1.[C:14](=O)(ON1C(=O)CCC1=O)[O:15]N1C(=O)CCC1=O.N1C=CC=CC=1.C(N(C(C)C)CC)(C)C.Cl.[CH2:48]1[C:56]2[C:51](=[CH:52][C:53]([C:57]([O:59][CH3:60])=[O:58])=[CH:54][CH:55]=2)[CH2:50][NH:49]1>C(#N)C.CN1CCCC1=O.O>[CH2:9]([NH:8][C:6]([C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:14]([N:49]2[CH2:50][C:51]3[C:56](=[CH:55][CH:54]=[C:53]([C:57]([O:59][CH3:60])=[O:58])[CH:52]=3)[CH2:48]2)=[O:15])=[CH:13][CH:12]=1)=[O:7])[CH2:10][CH3:11]

Participants

9

Reactant 5

HCID 1049PyridineHCID 81531Diisopropylethylamine2×HCID 4283444-amino-N-propylbenzamideHCID 676246Di(succinimido) carbonateHCID 19828495methyl 2,3-dihydro-1H-isoindole-5-carboxylate hydrochloride

Product 1

HCID 57509896Methyl 2-(4-(propylcarbamoyl)phenylcarbamoyl)isoindoline-5-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-amino-N-propylbenzamide (390 mg, 2.19 mmol), bis(2,5-dioxopyrrolidin-1-yl) carbonate (700 mg, 2.74 mmol), and pyridine (0.18 mL, 2.19 mmol) in acetonitrile (5 mL) was stirred at ambient temperature for 30 minutes. Diisopropylethylamine (0.85 mL, 6.6 mmol)) was added followed by a suspension of methyl isoindoline-5-carboxylate hydrochloride (538 mg, 2.52 mmol) and diisopropylethylamine (0.46 mL, 4.4 mmol) in 1-methyl-2-pyrrolidinone (8 mL) added dropwise via syringe over ˜5 minutes. The reaction became a suspension and was stirred 3 hours. The reaction was treated with water (30 mL) and the resulting suspension was stirred 5 minutes and filtered. The solid collected was washed with water and dried under vacuum to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.63 (s, 1H), 8.26 (t, J=5.6 Hz, 1H), 7.94-7.97 (m, 1H), 7.90-7.96 (m, 1H), 7.75-7.78 (m, 2H), 7.63-7.67 (m, 2H), 7.52 (d, J=7.9 Hz, 1H), 4.83-4.86 (m, 4H), 3.87 (s, 3H), 3.16-3.22 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, J=7.4 Hz, 3H); MS (ESI(+)) m/e 382 (M+H)+.

Workup

  1. additionadded dropwise via syringe over ˜5 minutes
  2. stirringthe resulting suspension was stirred 5 minutes
  3. filtrationfiltered
  4. customThe solid collected
  5. washwas washed with water
  6. customdried under vacuum

Sources & evidence

ORD record
ord-b9cf5fa28fe247d69dd1e813c90c7acf
Source dataset
uspto-grants-2016_04
Patent number
US09302989B2

Reaction notes

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