Thioanisole → HCID 71009378, compound

HRID 1527562Notes

Reaction equation

HRID 1527562 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]([N:21]1[CH2:25][C@H:24]([F:26])[CH2:23][C@H:22]1[C:27](=[O:38])[NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[F:37])=[O:20])[CH:13]=[C:12]2[C:39]([NH2:41])=[O:40])C1C=CC=CC=1.C1(SC)C=CC=CC=1>C(O)(C(F)(F)F)=O>[Cl:36][C:32]1[C:31]([F:37])=[C:30]([CH:35]=[CH:34][CH:33]=1)[CH2:29][NH:28][C:27]([C@@H:22]1[CH2:23][C@@H:24]([F:26])[CH2:25][N:21]1[C:19](=[O:20])[CH2:18][N:14]1[C:15]2[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=2)[C:12]([C:39]([NH2:41])=[O:40])=[CH:13]1)=[O:38]

Participants

4

Reactant 2

HCID 7520ThioanisoleHCID 68284523HCID 68284523, compound

Product 1

HCID 71009378HCID 71009378, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 5-benzyloxy-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indole-3-carboxylic acid amide Example 503 (148 mg, 0.255 mmol) in TFA (2.5 mL), cooled to 0° C., was added thioanisole (0.301 mL, 2.55 mmol), and the reaction mixture was stirred at RT for 3 h. Volatiles were evaporated under reduced pressure, and the residue was suspended in a saturated aqueous NaHCO3 solution, followed by freeze-drying in vacuo. The residue was suspended in a small amount of methanol and the solid was filtered off. The filtrate was purified by preparative HPLC (Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA). The title compound was obtained as a white solid. MS (LC/MS): 491 [M+H]+; 983 [2M+H]+; tR (HPLC, conditions b): 3.75 min.

Workup

  1. customVolatiles were evaporated under reduced pressure
  2. customby freeze-drying in vacuo
  3. filtrationthe solid was filtered off
  4. customThe filtrate was purified by preparative HPLC (Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-8f60a998de7840ed9e230002b46acd23
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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