4-Methylmorpholine → HCID 88630118, compound

HRID 2291381Notes

Reaction equation

HRID 2291381 reaction equation
[CH2:1]([O:4][C:5]([NH:7][C:8]1[S:9][CH:10]=[C:11](/[C:13](=[N:17]/[O:18][CH3:19])/[C:14]([OH:16])=O)[N:12]=1)=[O:6])[CH:2]=[CH2:3].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[Cl-].[CH2:39]([O:46][C:47]([C:49]1[CH2:56][N:55]2[N:51]([C:52](=[O:58])[CH:53]([NH2:57])[CH2:54]2)[C:50]=1[C:59]([O:61][CH2:62][CH:63]=[CH2:64])=[O:60])=[O:48])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)Cl.C(OCC)(=O)C>[CH2:39]([O:46][C:47]([C:49]1[CH2:56][N:55]2[N:51]([C:52](=[O:58])[CH:53]([NH:57][C:14](=[O:16])/[C:13](/[C:11]3[N:12]=[C:8]([NH:7][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[S:9][CH:10]=3)=[N:17]\[O:18][CH3:19])[CH2:54]2)[C:50]=1[C:59]([O:61][CH2:62][CH:63]=[CH2:64])=[O:60])=[O:48])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 14544664HCID 14544664, compoundHCID 21279976HCID 21279976, compound

Product 1

HCID 88630118HCID 88630118, compoundYield 67.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, 2-[2-(allyloxycarbonylamino)thiazol-4-yl]-2-(Z)-methoxyiminoacetic acid (231 mg, 0.81 mmol) was suspended in methylene chloride (5 ml) and the suspension was cooled to 0° C. 2-Chloro-4,6-dimethoxy-1,3,5-triazine (142 mg, 0.81 mmol) followed by N-methylmorpholine (0.09 ml, 0.81 mmol) were added and the solution was stirred at 0° C. for 30 minutes. A methylene chloride solution (10 ml) of allyl 3-(benzyloxycarbonyl)-7-(R,S)-amino-8-oxo-1,5-diazabicyclo[3.3.0]octa-2-ene-2-carboxylate chloride (0.81 mmol) followed by additional N-methylmorpholine (0.09 ml, 0.81 mmol) were added and the solution was stirred and allowed to warm gradually to room temperature over 1.5 hours. The methylene chloride was removed in vacuo and the resultant residue was flash chromatographed on silica gel eluted with 10% hexane:ethyl acetate to give 340 mg, 67% yield of the title compound: n.m.r. (90 MHz, CDCl3): δ 3.08 (dd, J=10.8 and 10.8, 1), 3.96 (s, 3), 3.99, 4.43 (ABq, J=12.6, 2), 3.88-4.28 (m, 2), 4.56-4.92 (m, 4), 5.16 (s, 2), 5.23 (d, J=9, 2), 5.42 (d, J=10.8, 2), 5.50-6.16 (m, 2), 7.10 (s, 1), 7.28 (br. s, 5), 8.09 (br. d, 1), 9.38 (br. s, 1); i.r. (CDCl3): 3025, 1731, 1704, 1557, 1386, 1369, 1277 cm-1 ; f.d.m.s. (m/e): M+ +1=625; u.v. (EtOH): εmax =264 (ε=10926), 338 (ε=6493); Anal. Calcd for C28H28N6O9S1 : Theory: C, 53.84; H, 4.52; N, 13.45; Found: C, 53.68; H, 4.59; N, 13.21.

Workup

  1. additionwere added
  2. additionwere added
  3. stirringthe solution was stirred
  4. temperatureto warm gradually to room temperature over 1.5 hours
  5. customThe methylene chloride was removed in vacuo
  6. customchromatographed on silica gel
  7. washeluted with 10% hexane

Sources & evidence

ORD record
ord-8dc75e26d51948ff955f9ab90120a659
Source dataset
uspto-grants-1989_01
Patent number
US04795815

Reaction notes

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