Diisopropylethylamine → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-2-(phenylsulfanyl)-1,3-thiazole-5-carboxamide Fumarate

HRID 2298361Notes

Reaction equation

HRID 2298361 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]1([S:31][C:32]2[S:33][C:34]([C:37]([OH:39])=O)=[CH:35][N:36]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl.Cl.[NH2:42][C@@H:43]1[CH:48]2[CH2:49][CH2:50][N:45]([CH2:46][CH2:47]2)[CH2:44]1.CCN(C(C)C)C(C)C.[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64]>CN(C=O)C.C(Cl)Cl>[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64].[N:45]12[CH2:50][CH2:49][CH:48]([CH2:47][CH2:46]1)[C@@H:43]([NH:42][C:37]([C:34]1[S:33][C:32]([S:31][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[N:36][CH:35]=1)=[O:39])[CH2:44]2

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 444972Fumaric AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12494972(R)-(+)-3-Aminoquinuclidine DihydrochlorideHCID 223504262-Phenylsulfanyl-thiazole-5-carboxylic acid

Product 1

HCID 10298317N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-2-(phenylsulfanyl)-1,3-thiazole-5-carboxamide FumarateYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

HATU (0.493 g, 1.30 mmol, 1 eq) is added to a solution of 2-phenylsulfanyl-thiazole-5-carboxylic acid (0.307 g, 1.30 mmol, 1 eq), (R)-(+)-3-aminoquinuclidine dihydrochloride (0.258 g, 1.30 mmol, 1 eq), and DIEA (0.677 mL, 3.89 mmol, 3 eq) in DMF (9.8 mL), the flask containing which was in an ice bath. The reaction is stirred overnight. CH2Cl2 is added, and the mixture is washed with water three times. The organic layer is dried over MgSO4, and the solvent removed in vacuo. The product is purified using a Biotage Flash 40M column (1% NH4OH/9% MeOH/90%CH2Cl2), affording a clear oil. The fumaric acid salt of the product is made, and recrystallized from MeOH and ether to give the product as a white crystalline solid (0.408 g, 72%). MS (ESI) for C17H19N3OS2 m/z 346.1 (M+H)+.

Workup

  1. additionthe flask containing which
  2. customwas in an ice bath
  3. washthe mixture is washed with water three times
  4. dry with materialThe organic layer is dried over MgSO4
  5. customthe solvent removed in vacuo
  6. customThe product is purified
  7. customaffording a clear oil
  8. customrecrystallized from MeOH and ether

Sources & evidence

ORD record
ord-0a7e7580584a4cc8a0849d64eeb61491
Source dataset
uspto-grants-2002_12
Patent number
US06492385B2

Reaction notes

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