Ethanol → 2-(2-(2-(3-(Benzyloxy)pyridin-2-ylamino)thiazol-4-yl)ethyl)isoindoline-1,3-dione

HRID 1426107Notes

Reaction equation

HRID 1426107 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]([NH2:18])=[S:17])=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:20][C:21](=O)[CH2:22][CH2:23][N:24]1[C:32](=[O:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]1=[O:34].C(N(CC)CC)C.C(O)C>O>[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]2[S:17][CH:20]=[C:21]([CH2:22][CH2:23][N:24]3[C:32](=[O:33])[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]3=[O:34])[N:18]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 37597442-(4-Bromo-3-oxobutyl)-1H-isoindole-1,3(2H)-dioneHCID 727056391-(3-(Benzyloxy)pyridin-2-yl)thiourea

Product 1

HCID 166620792-(2-(2-(3-(Benzyloxy)pyridin-2-ylamino)thiazol-4-yl)ethyl)isoindoline-1,3-dioneYield 98.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1-(3-(benzyloxy)pyridin-2-yl)thiourea (prepared according to Example 2, Steps A and B) (8.00 g, 30.8 mmol), 2-(4-bromo-3-oxobutyl)isoindoline-1,3-dione (12.8 g, 43.2 mmol; prepared according to J. Med. Chem. (1992) 35, 3239-3246), triethylamine (7.31 mL, 52.4 mmol), and ethanol (200 mL) was heated at reflux for 2 hours. The reaction mixture was cooled, diluted with water (200 mL), filtered, washed several times with water and hexanes, and dried. The product was recrystallized the solid from hexanes:methylene chloride (1:1, 250 mL) to afford 2-(2-(2-(3-(benzyloxy)pyridin-2-ylamino)thiazol-4-yl)ethyl)isoindoline-1,3-dione (13.8 g, 98.0% yield) as a white powder. 1H NMR (d6-DMSO) δ 9.93 (bs, 1H), 7.80-7.87 (m, 6H), 7.57 (d, 2H), 7.35-7.43 (m, 4H), 6.89 (m, 1H), 6.70 (s, 1H), 5.25 (s, 2H), 3.88 (t, 2H), 2.91 (t, 2H). Mass spectrum (apci) m/z=457 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered
  5. washwashed several times with water and hexanes
  6. customdried
  7. customThe product was recrystallized the solid from hexanes:methylene chloride (1:1, 250 mL)

Sources & evidence

ORD record
ord-b7c4c3a6b6d044338c6f84f93e6e0540
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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