HCID 20711242, compound → HCID 57634024, compound

HRID 2109733Notes

Reaction equation

HRID 2109733 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:10][NH:11][C:12]([NH2:14])=[S:13])=[CH:4][CH:3]=1.Br[CH:24]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[C:32]([F:37])[CH:31]=1)[C:25](OCC)=[O:26]>C(O)C.C(N(C(C)C)CC)(C)C>[C:18]([O:17][C:16](=[O:22])[NH:15][C@@H:9]([CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[CH2:10][NH:11][C:12]1[S:13][C:24]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[C:32]([F:37])[CH:31]=2)=[C:25]([OH:26])[N:14]=1)([CH3:19])([CH3:21])[CH3:20]

Participants

5

Reactant 2

HCID 20711242HCID 20711242, compoundHCID 57633943HCID 57633943, compound

Product 1

HCID 57634024HCID 57634024, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-tert-butyl 3-(4-chlorophenyl)-1-thioureidopropan-2-ylcarbamate (0.585 g, 1.70 mmol) and ethyl 2-bromo-2-(3,4-difluorophenyl)acetate (0.500 g, 1.79 mmol) in ethyl alcohol (2 mL) and diisopropylethylamine (0.3 mL) in a sealed vial (Biotage microwave vial, 5 mL) with a magnetic stirring bar was heated in a microwave oven (Initiator, Biotage) at 120° C. for 15 minutes. After cooling to ambient temperature, the volatiles were removed in vacuum. The residue was partitioned between EtOAc and water. The combined organic portions were washed with brine. The crude product was purified by flash column chromatography (20% of EtOAc in hexanes for 5 minutes, 20% to 100% of EtOAc in hexanes over 23 minutes). The product was obtained as a white solid, 0.201 g, 24%. 1H NMR (300 MHz, CD3OD) δ 1.22-1.39 (m, 9H), 2.52-2.97 (m, 2H), 3.35-3.60 (m, 1H), 3.64-3.85 (m, 1H), 3.92-4.24 (m, 1H), 7.11-7.46 (m, 7H). LCMS (API-ES): 496.1/498.1 (M++H), chloro pattern.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe volatiles were removed in vacuum
  3. customThe residue was partitioned between EtOAc and water
  4. washThe combined organic portions were washed with brine
  5. customThe crude product was purified by flash column chromatography (20% of EtOAc in hexanes for 5 minutes, 20% to 100% of EtOAc in hexanes over 23 minutes)
  6. customThe product was obtained as a white solid, 0.201 g, 24%

Sources & evidence

ORD record
ord-ceea7bd1cf7a448db36b19617a7da33b
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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