Diisopropylethylamine → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1011716Notes

Reaction equation

HRID 1011716 reaction equation
CC[N:3]([CH:7]([CH3:9])C)[CH:4](C)C.[F:10][CH2:11][CH:12]([O:15][C:16]1[CH:17]=[C:18]([O:31][C:32]2[N:33]=[CH:34][C:35]([C:38](O)=[O:39])=[N:36][CH:37]=2)[CH:19]=[C:20]([C:22]([NH:24][C:25]2[CH:29]=[CH:28][N:27]([CH3:30])[N:26]=2)=[O:23])[CH:21]=1)[CH2:13][F:14].Cl.N1CCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[N:3]1([C:38]([C:35]2[N:36]=[CH:37][C:32]([O:31][C:18]3[CH:19]=[C:20]([CH:21]=[C:16]([O:15][CH:12]([CH2:13][F:14])[CH2:11][F:10])[CH:17]=3)[C:22]([NH:24][C:25]3[CH:29]=[CH:28][N:27]([CH3:30])[N:26]=3)=[O:23])=[N:33][CH:34]=2)=[O:39])[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 591271395-[(3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid

Product 1

HCID 160396443-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 35.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (0.45 mL, 2.58 mmol) was added to a mixture of 5-[(3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid (0.28 g, 0.65 mmol), azetidine hydrochloride (121 mg, 1.29 mmol) and HATU (516 mg, 1.36 mmol) in DMF (5 mL) and stirred at RT for 72 hours. Ethyl acetate (40 mL) was added and the organics washed with water (2×30 mL), brine (30 mL), dried (MgSO4), filtered and reduced in vacuo to give a yellow oil which was chromatographed on silica, eluting with 0-100% ethyl acetate in isohexane, to give the desired compound (109 mg). 1H NMR δ (CDCl3): 2.32 (quin, 2H), 3.70 (s, 3H), 4.19 (t, 2H), 4.54-4.72 (m, 7H), 6.73 (s, 1H), 6.93 (t, 1H), 7.22 (d, 1H), 7.25 (s, 1H), 7.34 (s, 1H), 8.28 (d, 1H), 8.78 (d, 1H), 8.80 (s, 1H); m/z 473 (M+H)+

Workup

  1. washthe organics washed with water (2×30 mL), brine (30 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customto give a yellow oil which
  5. customwas chromatographed on silica
  6. washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-2ba7135eddb14b6586c41ab2a92a7bd4
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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