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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 1989932
Notes
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Reaction equation

HRID 1989932 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 16039644
3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide
Yield 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-0f8e43c0acc94db3b547cc839d93175c
Source dataset
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07642263B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes