Hydrochloric Acid → HCID 178467193, compound

HRID 1527587Notes

Reaction equation

HRID 1527587 reaction equation
[Cl:1][C:2]1[C:3]([F:35])=[C:4]([CH:32]=[CH:33][CH:34]=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:31])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=2)[C:19]([C:28](=[O:30])[CH3:29])=[CH:18]1)=[O:8].[N-:36]=[N+:37]=[N-:38].[Na+].Cl>O.C(O)(C)C.[Br-].[Zn+2].[Br-]>[Cl:1][C:2]1[C:3]([F:35])=[C:4]([CH:32]=[CH:33][CH:34]=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:31])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]3[NH:38][N:37]=[N:36][N:27]=3)[CH:24]=2)[C:19]([C:28](=[O:30])[CH3:29])=[CH:18]1)=[O:8]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 68283992HCID 68283992, compound

Product 1

HCID 178467193HCID 178467193, compound

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

To a suspension of (2S,4R)-1-[2-(3-acetyl-6-cyano-indol-1-yl)-acetyl]-4-fluoro-pyrrolidine-2-carboxylic acid 3-chloro-2-fluoro-benzylamide (prepared as described in Example 616 (45.0 mg, 0.09 mmol) in water (2 mL) and isopropanol (1 mL) at RT were added sodium azide (24.0 mg, 0.360 mmol) and zinc bromide (40.0 mg, 0.180 mmol). The mixture was heated to 130° C. for 10 h in a microwave apparatus (Personnal Chemistry, Biotage). After cooling to RT, a 6N HCl solution was added to the mixture, followed by extraction with EtOAc (3×). The combined organics were washed with brine, dried (phase separator) and concentrated in vacuo. Purification of the residue by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) afforded after lyophilization the title compound as solid. MS (LC/MS): 542.0 [M+H]+; tR (HPLC conditions k): 3.15 min.

Workup

  1. customprepared
  2. temperatureAfter cooling to RT
  3. extractionfollowed by extraction with EtOAc (3×)
  4. washThe combined organics were washed with brine
  5. customdried (phase separator)
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min)

Sources & evidence

ORD record
ord-b8e9284dc5d74e1787698c6d1e515f1d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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