Diisopropylethylamine → 3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20503Notes

Reaction equation

HRID 20503 reaction equation
CCN(C(C)C)C(C)C.[N:10]1([C:14]([C:16]2[CH:36]=[CH:35][C:19]([O:20][C:21]3[CH:22]=[C:23]([CH:27]=[C:28]([O:30][C@@H:31]([CH3:34])[CH2:32][OH:33])[CH:29]=3)[C:24](O)=[O:25])=[C:18]([F:37])[CH:17]=2)=[O:15])[CH2:13][CH2:12][CH2:11]1.[CH3:38][N:39]1[CH:43]=[CH:42][C:41]([NH2:44])=[N:40]1>CN(C=O)C>[N:10]1([C:14]([C:16]2[CH:36]=[CH:35][C:19]([O:20][C:21]3[CH:22]=[C:23]([CH:27]=[C:28]([O:30][C@@H:31]([CH3:34])[CH2:32][OH:33])[CH:29]=3)[C:24]([NH:44][C:41]3[CH:42]=[CH:43][N:39]([CH3:38])[N:40]=3)=[O:25])=[C:18]([F:37])[CH:17]=2)=[O:15])[CH2:11][CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 593468833-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid

Product 1

HCID 115328673-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 53.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (93 mg, 0.72 mmol; 4.0 equivalents) was added to a suspension of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid (70 mg), HATU-(144 mmol; 2.1 equivalents) and 1-methyl-1-H-pyrazole-3-amine (26 mg, 0.27 mmol, 1.5 equivalents) in DMF (2 mL). The resulting mixture was stirred at ambient temperature for 16 hours. The DMF was removed in vacuo, water was added and the mixture extracted with ethyl acetate. The extracts were combined, washed with brine, dried (MgSO4), filtered, and evaporated in vacuo to give the crude product which was chromatographed, eluting with 0-100% ethyl acetate in isohexane, to give desired compound (45 mg).

Workup

  1. customThe DMF was removed in vacuo, water
  2. additionwas added
  3. extractionthe mixture extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give the crude product which
  9. customwas chromatographed
  10. washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-947bfa7d107f4af2b8ad5bb9118c5d7b
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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