C-(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine → methyl {[2-hydroxy-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzoyl]methylamino}acetate

HRID 1528214Notes

Reaction equation

HRID 1528214 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C@H:7]([NH2:13])[C:8]2([CH3:12])[CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.[OH:14][C:15]1[C:29]([NH:30][C:31]2[C:34](=O)[C:33](=[O:36])[C:32]=2[O:37]C)=[CH:28][CH:27]=[CH:26][C:16]=1[C:17]([CH2:19][NH:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18]>CO>[OH:14][C:15]1[C:29]([NH:30][C:31]2[C:32](=[O:37])[C:33](=[O:36])[C:34]=2[NH:13][C@@H:7]([C:5]2[O:6][C:2]([CH3:1])=[CH:3][CH:4]=2)[C:8]2([CH3:12])[CH2:9][O:10][CH2:11]2)=[CH:28][CH:27]=[CH:26][C:16]=1[C:17]([CH2:19][NH:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18]

Participants

4

Reactant 2

HCID 89525580C-(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamineHCID 131733218Methyl {[2-hydroxy-3-(2-methoxy-3,4-dioxocyclobut-1-enylamino)benzoyl]methylamino}acetate

Product 1

HCID 131733219methyl {[2-hydroxy-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzoyl]methylamino}acetateYield 78%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 371 mg (2.07 mmol, 1.2 eq) of C—(R)-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine (prepared in EXAMPLE 50, steps 1 to 4) and 600 mg (1.7 mmol, 1 eq) of methyl {[2-hydroxy-3-(2-methoxy-3,4-dioxocyclobut-1-enylamino)benzoyl]methylamino}acetate in 24 ml of methanol was heated at 60° C. for 16 hours. The methanol was evaporated off and the residue was chromatographed on silica gel, eluent dichloromethane/ethyl acetate (75/25). The paste obtained was crystallized from diethyl ether and heptane and dried under vacuum at 40° C. 660 mg of methyl {[2-hydroxy-3-(2-{[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzoyl]methylamino}acetate were obtained in the form of a pale yellow solid. Yield=76%.

Workup

  1. customThe methanol was evaporated off
  2. customthe residue was chromatographed on silica gel, eluent dichloromethane/ethyl acetate (75/25)
  3. customThe paste obtained
  4. customwas crystallized from diethyl ether and heptane
  5. customdried under vacuum at 40° C

Sources & evidence

ORD record
ord-69d4d6645a4746c99b9a69c67a7b15ff
Source dataset
uspto-grants-2015_07
Patent number
US09090596B2

Reaction notes

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