Chloroacetic Acid → HCID 69177920, compound

HRID 1624309Notes

Reaction equation

HRID 1624309 reaction equation
[N:1]1[C:10]2[C@@H:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl[CH2:28][C:29]1[N:33]([CH3:34])[C:32]2[CH:35]=[CH:36][CH:37]=[CH:38][C:31]=2[N:30]=1.CNC1C=CC=CC=1N.ClCC(O)=O.C(N(C(C)C)CC)(C)C.[I-].[K+]>C(#N)C>[CH3:34][N:33]1[C:32]2[CH:35]=[CH:36][CH:37]=[CH:38][C:31]=2[N:30]=[C:29]1[CH2:28][N:11]([CH:9]1[C:10]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:6][CH2:7][CH2:8]1)[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24](=[O:25])[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]1=[O:26]

Participants

8

Reactant 6

HCID 300Chloroacetic AcidHCID 4875Potassium IodideHCID 78498N-Methyl-o-phenylenediamineHCID 81531DiisopropylethylamineHCID 2480442-(Chloromethyl)-1-methylbenzimidazoleHCID 513586312-(4-{[(8S)-5,6,7,8-Tetrahydroquinolin-8-yl]amino}butyl)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 69177920HCID 69177920, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-2-[4-(5,6,7,8-tetrahydro-quinolin-8-ylamino)-butyl]-isoindole-1,3-dione (3.89 g, 11.1 mmol) in acetonitrile (111 ml) was added 2-chloromethyl-1-methyl-1H-benzoimidazole (prepared by reaction of N-methyl-ortho-phenylenediamine with chloroacetic acid according to literature procedure Phillips, M. A. J. Chem. Soc. 1928, 2393; Goker, H.; Kus, C. Arch. Pharm. (Weinheim) 1995, 328, 425-430) (2.42 g, 13.4 mmol), diisopropylethylamine (1.93 ml, 11.1 ml), and potassium iodide (0.18 g, 1.11 ml). The mixture was stirred for 16 hours at 50° C. The mixture was concentrated, redissolved in methylene chloride (200 ml) and diluted with saturated NaCl (400 ml). The reaction was extracted with methylene chloride (3×300 ml) and the combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a dark red oil. Purification via column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 95:4:1, v/v/v) afforded the product as a light red foam (5.12 g, 77%). 1H NMR (CDCl3) δ 1.63 (m, 8H), 2.65 (m, 4H), 3.54 (m, 2H), 4.10 (m, 6H), 6.98 (dd, 1H, J=7.89, 4.38 Hz), 7.21 (m, 4H), 7.71 (m, 5H), 8.49 (d, 1H, J=3.95 Hz).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionredissolved in methylene chloride (200 ml)
  3. additiondiluted with saturated NaCl (400 ml)
  4. extractionThe reaction was extracted with methylene chloride (3×300 ml)
  5. dry with materialthe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a dark red oil
  9. customPurification via column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 95:4:1, v/v/v)

Sources & evidence

ORD record
ord-d89bcc0715004968ae3486d4f96470eb
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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