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Diisopropylethylamine → HCID 18180487, compound

HRID 2298381
Notes
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Reaction equation

HRID 2298381 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.Cl.Cl.[CH3:12][CH:13]1[CH:18]([NH2:19])[CH:17]2[CH2:20][CH2:21][N:14]1[CH2:15][CH2:16]2.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.C([O-])(O)=O.[Na+]>CC#N.CCOC(C)=O>[Br:1][C:2]1[S:6][C:5]([C:7]([NH:19][CH:18]2[CH:17]3[CH2:20][CH2:21][N:14]([CH2:15][CH2:16]3)[CH:13]2[CH3:12])=[O:9])=[CH:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 3491155-Bromothiophene-2-carboxylic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 220470632-Methyl-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride

Product 1

HCID 18180487
HCID 18180487, compound
Yield 49%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-bromothiophene-2-carboxylic acid (1.63 g, 7.88 mmol, 1 eq), the product from Step 158d (1.68 g, 7.88 mmol, 1 eq) and HATU (2.97 g, 7.81 mmol, 1 eq) are suspended in 60 mL CH3CN. The mixture is cooled in an ice bath and DIEA (8.2 mL, 47.28 mmol, 6 eq) is added dropwise. The mixture is allowed to warm to room temperature and stirred overnight. EtOAc and satd NaHCO3 are added. The aqueous layer is extracted with EtOAc. The combined organic layers are washed with 1N NaOH, dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography using a Biotage Flash 40S column (90:9:1 CHCl3/MeOH/NH4OH) to provide 1.26 g (49%) of 5-bromo-N-(2-methyl-1-azabicyclo[2.2.2]oct-3-yl)thiophene-2-carboxamide as a trans/cis mixture of isomers. The p-toluenesulfonic acid salt of the product is made and recrystallized from IPA/ether to give the product as light yellow solid. MS (ESI) for C13H17BrN2OS m/z 328.9/330.9 (M+H)+. Reverse phase HPLC (ZORBAX Eclipse XDB-C8, 4.6mm×15 cm, 80:12:8 H2O/CH3CN/IPA) revealed a 95:5 trans/cis mixture of isomers.

Workup

  1. temperatureThe mixture is cooled in an ice bath
  2. extractionThe aqueous layer is extracted with EtOAc
  3. washThe combined organic layers are washed with 1N NaOH
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-3f1f796265ff43efb2f792554b6e8cf8
Source dataset
uspto-grants-2002_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06492385B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes