Diisopropylethylamine → 3-[4-(2-Azabicyclo[2.1.1]hex-2-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20606Notes

Reaction equation

HRID 20606 reaction equation
CC[N:3]([CH:7]([CH3:9])[CH3:8])[CH:4]([CH3:6])C.[F:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[O:20][C:21]1[CH:26]=[C:25]([C:27]([NH:29][C:30]2[CH:34]=[CH:33][N:32]([CH3:35])[N:31]=2)=[O:28])[CH:24]=[C:23]([O:36][C@@H:37]([CH3:40])[CH2:38][OH:39])[CH:22]=1)[C:14](O)=[O:15].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C12CC(C1)CN2>CN(C=O)C.C(OCC)(=O)C>[CH:7]12[CH2:8][CH:6]([CH2:9]1)[CH2:4][N:3]2[C:14]([C:13]1[CH:17]=[CH:18][C:19]([O:20][C:21]2[CH:26]=[C:25]([CH:24]=[C:23]([O:36][C@@H:37]([CH3:40])[CH2:38][OH:39])[CH:22]=2)[C:27]([NH:29][C:30]2[CH:34]=[CH:33][N:32]([CH3:35])[N:31]=2)=[O:28])=[C:11]([F:10])[CH:12]=1)=[O:15]

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 552197462-Azabicyclo(2.1.1)hexane hydrochlorideHCID 593469353-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)benzoic acid

Product 1

HCID 117129523-[4-(2-Azabicyclo[2.1.1]hex-2-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 19.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (0.80 mL, 4.32 mmol) was added to a suspension of 3-fluoro-4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenoxy)benzoic acid (230 mg, 0.54 mmol), HATU (430 mg, 1.29 mmol) and 2-azabicyclo[2.1.1]hexane hydrochloride salt (96 mg, 0.81 mmol) in DMF (4 mL) and the mixture stirred at RT for 24 hours. Ethyl acetate was added and washed with water (3×30 mL), brine (30 mL), dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-10% methanol in DCM, to give the desired compound (51 mg).

Workup

  1. washwashed with water (3×30 mL), brine (30 mL)
  2. dry with materialdried (MgSO4)
  3. customevaporated to a residue which
  4. customwas chromatographed on silica
  5. washeluting with a gradient of 0-10% methanol in DCM

Sources & evidence

ORD record
ord-305ea28f7fa947098177eaeb1224b122
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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