Triphenylphosphine → 2-(4-Chloro-phenyl)-5-{3-methoxy-4-[2-(3-oxo-morpholin-4-yl)-ethoxy]-phenyl}-5H-thiazolo[5,4-c]pyridin-4-one

HRID 601533Notes

Reaction equation

HRID 601533 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:26])[N:12]([C:17]4[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([O:24][CH3:25])[CH:18]=4)[CH:13]=[CH:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1.O[CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][O:33][CH2:32][C:31]1=[O:36].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:26])[N:12]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH2:28][CH2:29][N:30]5[CH2:35][CH2:34][O:33][CH2:32][C:31]5=[O:36])=[C:19]([O:24][CH3:25])[CH:18]=4)[CH:13]=[CH:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 152874004-(2-Hydroxyethyl)morpholin-3-oneHCID 575017652-(4-Chloro-phenyl)-5-(4-hydroxy-3-methoxy-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 116991542-(4-Chloro-phenyl)-5-{3-methoxy-4-[2-(3-oxo-morpholin-4-yl)-ethoxy]-phenyl}-5H-thiazolo[5,4-c]pyridin-4-oneYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Combine 2-(4-chloro-phenyl)-5-(4-hydroxy-3-methoxy-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one (0.70 g, 1.82 mmol), 4-(2-hydroxy-ethyl)-morpholin-3-one (0.50 g, 3.45 mmol) and triphenylphosphine (0.50 g, 1.90 mmol) in THF (10.0 mL), stir for 10 min and add DIAD (0.77 g, 3.81 mmol). Heat to 80° C. for 2 days, cool the reaction mixture, and dilute with water. Extract with CH2Cl2 (2×), combine the organics, dry, and concentrate under vacuum. Purify the product by flash chromatography using 0-10% MeOH in CH2Cl2 to give the title compound (0.40 g, 43%). MS (ES+) 512.0 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 8.01 (d, 2H, J=8.6 Hz), 7.47 (d, 2H, J=8.6 Hz), 7.40 (d, 1H, J=7.5 Hz), 6.98-6.95 (m, 3H), 6.91 (dd, 1H, J=8.6, 2.4 Hz), 4.27 (t, 2H, J=5.2 Hz), 4.17 (s, 2H), 3.89-3.81 (m, 7H), 3.68 (t, 2H, J=5.1 Hz).

Workup

  1. temperaturecool the reaction mixture
  2. extractionExtract with CH2Cl2 (2×)
  3. customdry
  4. concentrationconcentrate under vacuum
  5. customPurify the product by flash chromatography

Sources & evidence

ORD record
ord-4c3de90bb45841b39a2539f603bbc3c3
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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