Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate → methyl (1aS,7bR)-5-[2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 927979Notes

Reaction equation

HRID 927979 reaction equation
[NH2:1][C:2]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]2[C:5]([CH:6]3[CH2:16][CH:7]3[CH2:8][O:9]2)=[CH:4][CH:3]=1.[CH2:17]([N:19]1[CH2:23][CH2:22][C@@H:21]([CH2:24][C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[S:32](Cl)(=[O:34])=[O:33])[CH2:20]1)[CH3:18]>C(Cl)Cl.N1C=CC=CC=1>[CH2:17]([N:19]1[CH2:23][CH2:22][C@@H:21]([CH2:24][C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[S:32]([NH:1][C:2]2[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]3[C:5]([C@@H:6]4[CH2:16][C@@H:7]4[CH2:8][O:9]3)=[CH:4][CH:3]=2)(=[O:33])=[O:34])[CH2:20]1)[CH3:18]

Participants

5

Reactant 2

HCID 86713293Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×HCID 867133192-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonyl chloride2×

Product 1

HCID 86713318methyl (1aS,7bR)-5-[2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 22.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 42, 0.257 g) in DCM (10 mL) and pyridine (5 mL) was treated with a solution of 2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonyl chloride (Intermediate 96, 0.36 g) in DCM (10 mL) and the mixture was stirred at room temperature overnight. The resultant mixture was evaporated to dryness and the residue was re-dissolved in DCM, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-10%, then flushed with 100% methanol to give methyl (1aS,7bR)-5-[2-((R)-1-ethylpyrrolidin-3-ylmethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.13 g) as a gum.

Workup

  1. customThe resultant mixture was evaporated to dryness
  2. dissolutionthe residue was re-dissolved in DCM
  3. washwashed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of methanol and DCM with a gradient of 0-10%
  9. customflushed with 100% methanol

Sources & evidence

ORD record
ord-b64590fc35d34dcf9b35c9a8e1f4d59e
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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