Sulfuric acid magnesium salt (1:1) → HCID 16066323, compound

HRID 2244663Notes

Reaction equation

HRID 2244663 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])=[CH:4][C:3]=1[F:15].C[Al](C)C.C[O:21][C:22]([C@H:24]1[CH2:28][C@H:27]([OH:29])[C@@H:26]([NH:30][C:31]([C:33]2[S:34][C:35]([Cl:38])=[CH:36][CH:37]=2)=[O:32])[CH2:25]1)=O.[O-]S([O-])(=O)=O.[Mg+2]>O1CCOCC1.O>[F:15][C:3]1[CH:4]=[C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:6]=[CH:7][C:2]=1[NH:1][C:22]([C@@H:24]1[CH2:25][C@H:26]([NH:30][C:31]([C:33]2[S:34][C:35]([Cl:38])=[CH:36][CH:37]=2)=[O:32])[C@@H:27]([OH:29])[CH2:28]1)=[O:21]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 16682925TrimethylaluminumHCID 221815481-(4-Amino-3-fluorophenyl)pyridin-2-oneHCID 58826431(1R,3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-cyclopentanecarboxylic acid methyl ester

Product 1

HCID 16066323HCID 16066323, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred suspension of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (296 mg; CAS 536747-52-1, prepared according to C. F. Bigge et al., patent application WO 2003045912) at r.t. in dioxane (3 ml) under an argon atmosphere was added carefully trimethyl aluminium solution (0.72 ml; 2M in heptane). After stirring for 2 hrs at r.t., a solution of (1R,3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-cyclopentane-carboxylic acid methyl ester (110 mg) in dioxane (3 ml) was added. The mixture was heated to 100° C. and stirring at that temperature was continued for 24 h. The mixture was cooled to r.t. and water (0.8 ml) was added. After 15 min stirring, MgSO4 was added and stirring was continued for another 15 min. The solids were filtered off and washed with dichloromethane. The filtrate was concentrated. The crude product was isolated by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1) to give 5-chloro-thiophene-2-carboxylic acid {(1S,2S,4R)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-2-hydroxy-cyclopentyl}-amide (81 mg) as light yellow solid. MS: 476.0 ([M+H]+).

Workup

  1. temperatureThe mixture was heated to 100° C.
  2. stirringstirring at that temperature
  3. waitwas continued for 24 h
  4. temperatureThe mixture was cooled to r.t.
  5. stirringAfter 15 min stirring
  6. stirringstirring
  7. waitwas continued for another 15 min
  8. filtrationThe solids were filtered off
  9. washwashed with dichloromethane
  10. concentrationThe filtrate was concentrated
  11. customThe crude product was isolated by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-98aa84237a6d429cba9886cf3a1d7ac6
Source dataset
uspto-grants-2010_03
Patent number
US07678917B2

Reaction notes

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