Diisopropylethylamine → (R)-N-(1-(5-bromo-2-(methylthio)pyrimidin-4-yl)-2-(3,5-difluorophenyl)ethyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide

HRID 2170323Notes

Reaction equation

HRID 2170323 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]([CH2:12][C:13]([OH:15])=O)[N:4]=1.Cl.[Br:19][C:20]1[C:21]([C@H:28]([NH2:38])[CH2:29][C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[CH:31]=2)=[N:22][C:23]([S:26][CH3:27])=[N:24][CH:25]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:19][C:20]1[C:21]([C@H:28]([NH:38][C:13](=[O:15])[CH2:12][N:5]2[C:6]3[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=3[C:3]([C:2]([F:1])([F:17])[F:16])=[N:4]2)[CH2:29][C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[CH:31]=2)=[N:22][C:23]([S:26][CH3:27])=[N:24][CH:25]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 788039[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90312062(R)-1-(5-bromo-2-(methylthio)pyrimidin-4-yl)-2-(3,5-difluorophenyl)ethanamine hydrochloride

Product 1

HCID 90281265(R)-N-(1-(5-bromo-2-(methylthio)pyrimidin-4-yl)-2-(3,5-difluorophenyl)ethyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-(3-(Trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetic acid (124 mg, 0.5 mmol) and 11F (200 mg, 0.5 mmol) were dissolved in 3 mL of DMF and cooled down to 0° C. To it were added N,N-diisopropylethylamine (435 μL, 2.5 mmol) and HATU (228 mg, 0.6 mmol). The reaction mixture was stirred at 0° C. for 5 minutes, and then partitioned between EtOAc and 5% LiCl aqueous solution. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated. The residue was dissolved in methylene chloride and to it added hexanes. The precipitate was collected by vacuum filtration and dried under high vacuum overnight to afford the title compound 11G. MS (m/z) 592.25 [M+H]+.

Workup

  1. custompartitioned between EtOAc and 5% LiCl aqueous solution
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in methylene chloride and to it
  8. additionadded hexanes
  9. filtrationThe precipitate was collected by vacuum filtration
  10. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-f93852a034804e469a1d31f29fb0eb0e
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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