Water → HCID 68750302, compound

HRID 623339Notes

Reaction equation

HRID 623339 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([C@@H:11]2[NH:15][C@@H:14]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@:13]3([C:28]4[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[C@H:12]2[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=2[F:38])=[O:10])[CH2:4][CH2:3]1.[C:39](Cl)(=[O:41])[CH3:40].[OH2:43].[C:44](OCC)(=[O:46])[CH3:45].N1[CH:55]=[CH:54]C=CC=1>>[C:39]([N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[C@@:13]2([C@@H:12]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=3[F:38])[C@H:11]([C:9]([NH:8][CH:5]3[CH2:6][CH2:7][CH:2]([O:1][C:44](=[O:46])[CH3:45])[CH2:3][CH2:4]3)=[O:10])[N:15]([C:54](=[O:43])[CH3:55])[C@H:14]2[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:21]1=[O:30])(=[O:41])[CH3:40]

Participants

6

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 178444601HCID 178444601, compound

Product 1

HCID 68750302HCID 68750302, compound

Procedure

To a solution of 281 mg (0.50 mmol) of (2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide in 5.0 mL of pyridine under argon, was added 178 μL (2.50 mmol) of acetyl chloride. The resulting mixture was stirred at room temperature for 4 days, upon which it was poured into a mixture of water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried with magnesium sulfate and then concentrated to dryness under reduced pressure. The residue was purified by flash chromatography on a 50 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 40 mL/min) followed by a second purification by flash chromatography on a 30 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 20 mL/min) 123 mg of acetic acid 4-{[(2′S,3R,4′S,5′R)-1,1′-diacetyl-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro [indole-3,3′-pyrrolidin]e-5′-carbonyl]-amino}-cyclohexyl ester were obtained as a white powder. LC-MS: tR (min)=1.19; [M+H]+: m/z 688; [M−H]−: m/z 686 (method A).

Workup

  1. customThe organic phase was separated
  2. extractionthe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe residue was purified by flash chromatography on a 50 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 40 mL/min)
  7. customfollowed by a second purification by flash chromatography on a 30 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 20 mL/min) 123 mg of acetic acid 4-{[(2′S,3R,4′S,5′R)-1,1′-diacetyl-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro [indole-3,3′-pyrrolidin]e-5′-carbonyl]-amino}-cyclohexyl ester
  8. customwere obtained as a white powder

Sources & evidence

ORD record
ord-fb2e4bde25e34b76806259ba5b9bf589
Source dataset
uspto-grants-2016_04
Patent number
US09302120B2

Reaction notes

Loading…