1,2-Dichloroethane → HCID 18463919, compound

HRID 2231088Notes

Reaction equation

HRID 2231088 reaction equation
C([O:4][C:5]1[C:28]([Cl:29])=[CH:27][C:8]([C:9]([NH:11][CH:12]2[C:18](=[O:19])[N:17]([CH:20](C)[C:21](O)=O)[N:16]([CH3:25])[C:15](=[O:26])[CH2:14][CH2:13]2)=[O:10])=[CH:7][C:6]=1[Cl:30])C=C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(O[C:49](=[O:65])[NH:50][CH:51]1[CH2:55][C:54](=[O:56])[O:53][CH:52]1[O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)C=C.CN1C(=O)CC(=O)N(C)C1=O>ClCCl.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>[CH2:58]([O:57][CH:52]1[CH:51]([NH:50][C:49]([CH:20]([N:17]2[C:18](=[O:19])[CH:12]([NH:11][C:9](=[O:10])[C:8]3[CH:27]=[C:28]([Cl:29])[C:5]([OH:4])=[C:6]([Cl:30])[CH:7]=3)[CH2:13][CH2:14][C:15](=[O:26])[N:16]2[CH3:25])[CH3:21])=[O:65])[CH2:55][C:54](=[O:56])[O:53]1)[C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 69860Dimethylbarbituric acid2×HCID 757711-HydroxybenzotriazoleHCID 18463927HCID 18463927, compoundHCID 22321532(2-Benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester

Product 1

HCID 18463919HCID 18463919, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[6-(4-allyloxy-3,5-dichloro-benzoylamino)-2-methyl-3,7-dioxo-[1,2]diazepan-1-yl]-propionic acid (18) (183 mg, 0.40 mmol) in dichloromethane was added HOBT (65 mg, 0.48 mmol) followed by EDC (123 mg, 0.64 mmol). The mixture was stirred at 0° C. for 30 min, then a solution of (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester (9, anti diastereomer) (140 mg, 0.48 mmol) in dichloromethane, charged with 1,3-dimethylbarbituric acid (DMBA) (75 mg, 0.48 mmol) and Pd(PPh3)4 (60 mg, 0.05 mmol) for 30 min, was added and the resulting mixture was stirred at room temperature for 5 hours. The second portion of DMBA (63 mg, 0.40 mmol) was added and the reaction mixture was continuously stirred at room temperature for 16 hours. The reaction was quenched with water and extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to give a pale yellow solid, that was purified by flash chromatography using dichloromethane/methanol (99/1 to 95/5) to afford 70 mg (29% yield) of the title compound as a mixture of diastereomers. 1H-NMR (500 MHz, CDCl3) δ 1.39-1.45 (m, 3H), 2.60-2.80 (m, 2H), 2.80-3.10 (m, 1H), 3.12-3.32 (m, 4H), 4.20-4.62 (m, 2H), 4.70-4.88 (m, 2H), 5.25-5.45 (m, 1H), 6.65-6.95 (m, 3H), 7.20-7.50 (m, 5H), 7.61 (s, 1H), 7.72 (d, 1H). Analytical HPLC: 10.86 and 10.98 min. LC-MS (ES+): m/e=607, 609 (M+H+).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature for 5 hours
  3. stirringthe reaction mixture was continuously stirred at room temperature for 16 hours
  4. customThe reaction was quenched with water
  5. extractionextracted with dichloromethane
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give a pale yellow solid, that
  10. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-d05419be4af84a38a2a448b1ba4772b4
Source dataset
uspto-grants-2002_07
Patent number
US06426413B1

Reaction notes

Loading…