Water → HCID 68283881, compound

HRID 1527570Notes

Reaction equation

HRID 1527570 reaction equation
[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:30])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][C:22]([OH:26])=[CH:23][CH:24]=2)[C:19]([C:27](=[O:29])[CH3:28])=[CH:18]1)=[O:8].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=1.O>CS(C)=O>[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:30])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][C:22]([O:26][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=3)=[CH:23][CH:24]=2)[C:19]([C:27](=[O:29])[CH3:28])=[CH:18]1)=[O:8]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 5642092-(Bromomethyl)pyridineHCID 68284042HCID 68284042, compound

Product 1

HCID 68283881HCID 68283881, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (2S,4R)-1-[2-(3-acetyl-5-hydroxy-indol-1-yl)-acetyl]-4-fluoro-pyrrolidine-2-carboxylic acid 3-chloro-2-fluoro-benzylamide Example 579 (60.0 mg, 0.122 mmol) in DMSO (2.5 mL) was treated with cesium carbonate (160 mg, 0.490 mmol). After stirring at RT for 5 min, 2-(bromomethyl)pyridine (31.0 mg, 0.122 mmol) was added to the reaction mixture and stirring was continued at RT for 16 h. Water was then added to the mixture to form a solid precipitate which was filtered off, washed with water and dried in vacuo. Purification by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) afforded after lyophilization of the purified fractions the title compound as a white solid. MS (LC/MS): 580/581 [M+H]+; tR (HPLC conditions k): 3.00 min.

Workup

  1. stirringstirring
  2. waitwas continued at RT for 16 h
  3. customto form a solid precipitate which
  4. filtrationwas filtered off
  5. washwashed with water
  6. customdried in vacuo
  7. customPurification by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-373ad7bf613c4d4fbbcbc8848fb49ec2
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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