1,2-Dichloroethane → HCID 9892498, compound

HRID 910015Notes

Reaction equation

HRID 910015 reaction equation
C[N:2]1[C:9](=O)[CH2:8][C:6](=[O:7])N(C)C1=O.[NH2:12][C:13]1[CH:36]=[CH:35][C:16]([C:17]([NH:19][CH:20]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:21]([N:23]2[CH2:27][CH2:26][CH2:25][CH:24]2[C:28](O)=[O:29])=[O:22])=[O:18])=[CH:15][C:14]=1[Cl:37].C(N(C(C)C)CC)(C)C.C(Cl)CCl.[CH3:51][CH2:52][O:53][C:54](C)=[O:55]>C(Cl)Cl.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:52]([O:53][CH:54]1[CH:9]([NH:2][C:28]([CH:24]2[CH2:25][CH2:26][CH2:27][N:23]2[C:21](=[O:22])[CH:20]([NH:19][C:17](=[O:18])[C:16]2[CH:35]=[CH:36][C:13]([NH2:12])=[C:14]([Cl:37])[CH:15]=2)[C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:8][C:6](=[O:7])[O:55]1)[CH3:51]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 8857Ethyl AcetateHCID 69860Dimethylbarbituric acidHCID 81531DiisopropylethylamineHCID 10156704851091-96-8

Product 1

HCID 9892498HCID 9892498, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6 (5.05 g, 22.0 mmol) in CH2Cl2 (50 mL) at 0° C. was added 1,3-dimethylbarbituric acid (DMBA) (3.78 g, 24.2 mmol) and Pd(PPh3)4 (0.15 g, 0.13 mmol). After 10 minutes, a solution of 5 (8.40 g, 22.0 mmol) in DMF (25 mL) was added followed by diisopropylethylamine (DIPEA) (7.66 mL, 44.1 mmol), (2.98 g, 22.0 mmol) and EDC (5.06 g, 26.4 mmol). The solution was stirred at 0° C. for 10 minutes then at room temperature for 18 hours. The reaction was diluted with EtOAc (200 mL), washed with 0.5N NaHSO4 (2×200 mL), 10% NaHCO3 (2×200 mL), saturated NaCl (1×150 mL), dried over anhydrous MgSO4, and evaporated to dryness. Flash column chromatography on silica gel using CH2Cl2/MeOH, (99/1 to 98/2%) afforded the title compound as a white solid (11.20 g, 77% yield): 1H-NMR (500 MHz, CDCl3) δ 1.08 (s, 9H), 1.27 (t, 3H), 1.85-1.99 (m, 1H), 2.00-2.06 (m. 1H), 2.07-2.18 (m, 1H), 2.32-2.48 (m, 2H), 2.78-2.89 (m, 1H), 3.62-3.76 (m, 2H), 3.82-3.96 (m, 2H), 4.39 (s, 1H), 4.54-4.60 (m, 1H), 4.62-4.76 (m, 1H), 4.85 (d, 1H), 6.57 (d, 1H), 6.73 (d, 1H), 7.38 (d, 1H), 7.49 (d, 1H), 7.72 (s, 1H). Analytical HPLC (cyano column): 13.10 min. LC-MS (ES+) m/e=509.4 (M+H), m.p.=96-99° C.

Workup

  1. waitat room temperature for 18 hours
  2. washwashed with 0.5N NaHSO4 (2×200 mL), 10% NaHCO3 (2×200 mL), saturated NaCl (1×150 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-2e461eea526745098da43be31eb58292
Source dataset
uspto-grants-2011_09
Patent number
US08022041B2

Reaction notes

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