Hydrochloric Acid → HCID 19592033, compound

HRID 1384712Notes

Reaction equation

HRID 1384712 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH:13]([N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27])[C:14](O)=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH2:34]([O:41][C:42]([N:44]1[CH:49]=[CH:48][CH:47]=[C:46]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[NH:45]1)=[O:43])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)(O)[O-].[Na+].Cl>CCOCC.ClCCl.C(OCC)(=O)C>[CH2:34]([O:41][C:42]([N:44]1[CH:49]=[CH:48][CH:47]=[C:46]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[N:45]1[C:14](=[O:15])[CH:13]([N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27])[CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])=[O:43])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 24819Phosphorus pentachlorideHCID 516892Sodium BicarbonateHCID 18465656HCID 18465656, compoundHCID 18465695HCID 18465695, compound

Product 1

HCID 19592033HCID 19592033, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of the acid 266 (1.32 g, 3.58 mmol) in dry ether (37 ml) was treated with phosphorus pentachloride (1.04 g, 5 mmol) and stirred at room temperature for 2 h. The solution was filtered to remove unreacted phosphorus pentachloride then evaporated to dryness. The residue was treated with dry toluene (25 ml) then evaporated to dryness. This process was repeated several times. The resulting oil was dissolved in dry dichloromethane (25 ml), cooled to 0° C. and treated with a solution of (3S) t-butyl 1-benzyloxycarbonylpyridazine-3-carboxylate (1.15 g, 3.58 mmol) in dry dichloromethane (2 ml) followed by 5% aqueous sodium bicarbonate solution (25 ml). The mixture was stirred rapidly at room temperature for 20 h then diluted with ethyl acetate (100 ml) and acidified to pH2 with 1M HCl. The organic phase was washed twice with dilute HCl solution then brine, dried (MgSO4) and concentrated. The resulting oil was purified by flash chromatography (2-20% ethyl acetate/dichloromethane then 10-20% methanol/dichloromethane) to afford (267), 1.25 g (52%) as a white powder: IR (KBr) 3367, 2955, 1722, 1517, 1455, 1387, 1369, 1251, 1153, 721; 1HÊNMR (CDCl3) δ 7.81 (2H, m), 7.74 (2H, m), 7.63 (1H, brs), 7.31 (10H, m), 5.46-4.76 (5H, m), 4.07-3.54 (4H, m), 2.4 (1H, m), 2.0-1.6 (3H, m), 1.40 (9H, s); MS (ES+), 671 (M+1), 693 (M+Na).

Workup

  1. filtrationThe solution was filtered
  2. customto remove unreacted phosphorus pentachloride
  3. customthen evaporated to dryness
  4. additionThe residue was treated with dry toluene (25 ml)
  5. customthen evaporated to dryness
  6. dissolutionThe resulting oil was dissolved in dry dichloromethane (25 ml)
  7. temperaturecooled to 0° C.
  8. stirringThe mixture was stirred rapidly at room temperature for 20 h
  9. washThe organic phase was washed twice with dilute HCl solution
  10. dry with materialbrine, dried (MgSO4)
  11. concentrationconcentrated
  12. customThe resulting oil was purified by flash chromatography (2-20% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-71ed62ee405943c2892237bf4716b212
Source dataset
uspto-grants-2001_07
Patent number
US06258948B1

Reaction notes

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