Diisopropylethylamine → 3-[4-(Azetidin-1-ylcarbonyl)phenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(5-methylpyrazin-2-yl)benzamide

HRID 20559

Reaction equation

HRID 20559 reaction equation
CC[N:3]([CH:7]([CH3:9])C)[CH:4](C)C.[OH:10][CH2:11][C@H:12]([CH3:40])[O:13][C:14]1[CH:15]=[C:16]([CH:27]=[C:28]([C:30]([NH:32][C:33]2[CH:38]=[N:37][C:36]([CH3:39])=[CH:35][N:34]=2)=[O:31])[CH:29]=1)[O:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.N1CCC1>CN(C=O)C.O>[N:3]1([C:22]([C:21]2[CH:20]=[CH:19][C:18]([O:17][C:16]3[CH:27]=[C:28]([CH:29]=[C:14]([O:13][C@@H:12]([CH3:40])[CH2:11][OH:10])[CH:15]=3)[C:30]([NH:32][C:33]3[CH:38]=[N:37][C:36]([CH3:39])=[CH:35][N:34]=3)=[O:31])=[CH:26][CH:25]=2)=[O:23])[CH2:4][CH2:9][CH2:7]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12308726Azetidine hydrochlorideHCID 593469134-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(5-methylpyrazin-2-yl)amino]carbonyl}phenoxy)benzoic acid

Product 1

HCID 115399033-[4-(Azetidin-1-ylcarbonyl)phenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(5-methylpyrazin-2-yl)benzamideYield 45.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.4 mL, 2.08 mmol) was added to a suspension of 4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(5-methylpyrazin-2-yl)amino]carbonyl}phenoxy)benzoic acid (110 mg, 0.26 mmol), HATU (210 mg, 0.55 mmol) and azetidine hydrochloride (49 mg, 0.52 mmol) in DMF (3 mL) and the mixture stirred at RT for 24 hours. Water (30 mL) was added and the mixture extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine, dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with 5% methanol in ethyl acetate, to give the desired compound (55 mg).

Workup

  1. extractionthe mixture extracted with ethyl acetate (3×15 mL)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. customevaporated to a residue which
  5. customwas chromatographed on silica
  6. washeluting with 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-ce28fb4cf5104a12903315a39263e4f3
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Linked notes

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