Diisopropylethylamine → HCID 57951460, compound

HRID 1013343Notes

Reaction equation

HRID 1013343 reaction equation
[C:1]1([C:7]2[CH2:11][C:10]3([CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)C(C)C)C.O.ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:62][CH2:63][C:64]1[CH:69]=[CH:68][C:67]([NH:70][S:71]([CH3:74])(=[O:73])=[O:72])=[C:66]([F:75])[CH:65]=1>C1COCC1>[F:75][C:66]1[CH:65]=[C:64]([CH:69]=[CH:68][C:67]=1[NH:70][S:71]([CH3:74])(=[O:73])=[O:72])[CH2:63][NH:62][C:17]([CH:14]1[CH2:13][CH2:12][C:10]2([O:9][N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:11]2)[CH2:16][CH2:15]1)=[O:19]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 21097526N-(4-(aminomethyl)-2-fluorophenyl)methanesulfonamideHCID 579514503-Phenyl-1-oxa-2-azaspiro[4.5]dec-2-ene-8-carboxylic acid

Product 1

HCID 57951460HCID 57951460, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Phenyl-1-oxa-2-azaspiro[4.5]dec-2-ene-8-carboxylic acid (400 mg, 1.54 mmol) was slowly added to a solution of N-ethyldiisopropylamine (662 g, 4.6 mmol), 1-hydroxybenzotriazole hydrate (206 mg, 1.54 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (496 mg, 1.54 mmol) and N-(4-aminomethyl-2-fluorophenyl)methanesulphonamide (336 mg, 1.54 mmol) in abs. THF (11 ml). The reaction mixture was stirred overnight and the solvent removed under vacuum. The residue was taken up in EtOAc (75 ml). The precipitate formed was removed by suction-filtration, washed with a small amount of ether and dried. The desired product 3-phenyl-1-oxa-2-azaspiro[4.5]dec-2-ene-8-carboxylic acid-3-fluoro-4-methanesulphonylaminobenzylamide was obtained as a cis isomer (89 mg, 13% of the theoretical amount). The organic phase was washed successively with sat. aq. NaCl solution, sat. aq. NaHCO3 solution, sat. aq. ammonium sulphate solution and sat. aq. NaCl solution, dried over magnesium sulphate and the solvent removed under vacuum. The residue was boiled up in EtOAc (2.5 ml) and DCM (1 ml). The precipitate formed was removed by suction-filtration and washed with a small amount of ether. The desired product 3-phenyl-1-oxa-2-azaspiro[4.5]dec-2-ene-8-carboxylic acid-3-fluoro-4-methanesulphonylaminobenzylamide was obtained as a trans isomer (138 mg, 19% of the theoretical amount).

Workup

  1. customthe solvent removed under vacuum
  2. customThe precipitate formed
  3. customwas removed by suction-filtration
  4. washwashed with a small amount of ether
  5. customdried

Sources & evidence

ORD record
ord-5b780eb760fb487c9f9e05a4d313743d
Source dataset
uspto-grants-2011_07
Patent number
US07981883B2

Reaction notes

Loading…