1-Hydroxybenzotriazole → HCID 18468955, compound

HRID 1871691Notes

Reaction equation

HRID 1871691 reaction equation
[Na].Cl.[CH2:3]([N:5]=[C:6]=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.N#N.C1(C[CH2:33][CH2:34][C:35]2[N:36]=[C:37]([C:40]([NH:42][C@H:43]([C:45]([NH:47][CH:48]3[CH2:52][C:51](=[O:53])[O:50][CH:49]3[O:54][CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[O:46])C)=[O:41])NC=2)C=CC=CC=1.C(OC(NC1CC(=O)OC1OCC1C=CC=CC=1)=O)C=C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH3:33][C:34]1[C:6]2[N:5]=[CH:3][N:42]([CH2:43][C:45]([NH:47][CH:48]3[CH2:52][C:51](=[O:53])[O:50][CH:49]3[O:54][CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[O:46])[C:40](=[O:41])[C:37]=2[NH:36][CH:35]=1

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5360545SodiumHCID 22321532(2-Benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl esterHCID 178462111HCID 178462111, compound

Product 1

HCID 18468955HCID 18468955, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A suspension of the sodium salt 41 (344 mg, 1.5 mmol) in dry DMF (15 ml) was treated with ethyl dimethylaminopropyl carbodiimide hydrochloride (373 mg, 1.95 mmol) and 1-hydroxybenzo-triazole (405 mg, 3.0 mmol). The mixture was kept at 25° C. for 1 h then (2R,S, 3S) N-allyloxycarbonyl-3-amino-2-benzyloxy-5-oxotetrahydrofuran (437 mg, 1.5 mmol; Chapman, Biorg. Med. Chem. Lett., 2, pp. 613-18 (1992)) and (Ph3P)2PdCl2 (25 mg) were added followed by the dropwise addition of n-tributyltin hydride (0.6 ml, 2.25 mmol). The resulting mixture was stirred at 25° C. for 1 h then water (20 ml) was added. The mixture was extracted with ethyl acetate (3×15 ml), and the combined organic extracts were washed with water (5 ml), dried (MgSO4), and concentrated to afford a mixture of diastereomers. Evaporation of the aqueous phase and purification of the residue by flash chromatography (5% methanol/chloroform) gave an additional quantity affording a total 182 mg of 42 (31%): m.p. 240-244° C.; IR (KBr) 3274, 1772, 1691, 1664, 1562; 1H NMR (d6 -DMSO) δ 11.81 (1H, s), 8.85 (0.6H, d, J=6.6), 8.72 (0.4H, d, J=7.4), 7.98 (0.6H, s), 7.95 (0.4H, s), 7.40-7.30 (5H, m), 7.20 (1H, d, J=2.2), 5.61 (0.4H, d, J=5.0), 5.46 (s), 4.85-4.60 (m), 4.28 (m), 3.20-2.35 (2H, m), 2.16 (3H, s).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×15 ml)
  2. washthe combined organic extracts were washed with water (5 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto afford
  6. additiona mixture of diastereomers
  7. customEvaporation of the aqueous phase and purification of the residue by flash chromatography (5% methanol/chloroform)
  8. customgave an additional quantity

Sources & evidence

ORD record
ord-c9452ec600304838a356727ad7edf0f6
Source dataset
uspto-grants-2000_08
Patent number
US06103711

Reaction notes

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