1,2-Dichloroethane → HCID 9892498, compound

HRID 2220109Notes

Reaction equation

HRID 2220109 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) δ1.08 (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-d36a7cd1659745388ba6f7a58aa52967
Source dataset
uspto-grants-2008_08
Patent number
US07417029B2

Reaction notes

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