HCID 59843177, compound → HCID 86624648, compound

HRID 2196560Notes

Reaction equation

HRID 2196560 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([C:14]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])=[O:15])=[CH:12][C:11]([C:26]([F:29])([F:28])[F:27])=[N:10]2)[CH:6]=[CH:7][CH:8]=1.FC1C=CC2NC(=O)N([C:40](=[S:51])[C@H:41]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH3:42])C=2C=1>CN(C=O)C.O>[CH3:25][O:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][NH:16][C:14]([C:13]1[N:9]([C:5]2[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=2)[CH2:2][NH:1][C:40](=[S:51])[C@@H:41]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:48])([CH3:47])[CH3:49])[CH3:42])[N:10]=[C:11]([C:26]([F:28])([F:29])[F:27])[CH:12]=1)=[O:15]

Participants

5

Reactant 2

HCID 59843177HCID 59843177, compoundHCID 86624649HCID 86624649, compound

Product 1

HCID 86624648HCID 86624648, compoundYield 38.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 58 (62 mg, 0.153 mmol) in dry DMF (0.3 mL) at 0° C. was added (R)-tert-butyl 1-(6-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-1-thioxopropan-2-ylcarbamate (57.2 mg, 0.169 mmol; J. Med. Chem.1999, 42, 2046-2052) in two equal portions over 10 minutes and the reaction was stirred at 0° C. for 2 hours and then at room temperature for 16 h. It was then diluted with water (˜15 mL) and extracted into dichloromethane using an “IST phase-separator.” The DCM extracts were combined and concentrated and the crude material purified by silica gel chromatography (Biotage 12M, 20% to 30% to 40% ethyl acetate in hexanes) to give 134 (35 mg, 0.059 mmol, 38.6% yield) as white solid. LRMS(ESI): (calc.) 529.3 (found) 614.3 (MNa)+.

Workup

  1. waitat room temperature for 16 h
  2. extractionextracted into dichloromethane using an “IST phase-separator
  3. concentrationconcentrated
  4. customthe crude material purified by silica gel chromatography (Biotage 12M, 20% to 30% to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2338f812e4954052b26479d275067605
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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