N,N-Dimethylglycine → 2-(dimethylamino)-1-(4-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethanone

HRID 2274832Notes

Reaction equation

HRID 2274832 reaction equation
[CH3:1][N:2]([CH2:4][C:5]([OH:7])=O)[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[F:42][C:43]1[CH:51]=[C:50]2[C:46]([C:47]([C:61]3[CH:62]=[N:63][N:64]([CH:66]4[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]4)[CH:65]=3)=[CH:48][N:49]2[S:52]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)(=[O:54])=[O:53])=[CH:45][CH:44]=1>C1COCC1>[CH3:1][N:2]([CH3:3])[CH2:4][C:5]([N:69]1[CH2:68][CH2:67][CH:66]([N:64]2[CH:65]=[C:61]([C:47]3[C:46]4[C:50](=[CH:51][C:43]([F:42])=[CH:44][CH:45]=4)[N:49]([S:52]([C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=4)(=[O:54])=[O:53])[CH:48]=3)[CH:62]=[N:63]2)[CH2:71][CH2:70]1)=[O:7]

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1180603056-fluoro-1-(phenylsulfonyl)-3-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-indole hydrochloride2×

Product 1

HCID 1180604062-(dimethylamino)-1-(4-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethanoneYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (dimethylamino)acetic acid (165 mg; 1.60 mmol), HATU (608 mg; 1.60 mmol), and DIPEA (619 mg; 4.80 mmol) in THF (25 mL) was added 6-fluoro-1-(phenylsulfonyl)-3-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-indole hydrochloride (Intermediate 17; 368 mg; 0.80 mmol) under nitrogen. The reaction mixture was stirred overnight, concentrated, dealed with saturated aqueous NaHCO3 (50 mL), extracted with EtOAc (50 ml×2). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated and purified by a silica gel chromatography (DCM/MeOH=20/1) to afford 400 mg (100%) of the title compound as a yellow oil.

Workup

  1. concentrationconcentrated
  2. extractionextracted with EtOAc (50 ml×2)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by a silica gel chromatography (DCM/MeOH=20/1)

Sources & evidence

ORD record
ord-573162a4cff94d409bff35387a6f4b34
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

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