Diisopropylethylamine → HCID 117899572, compound

HRID 522286Notes

Reaction equation

HRID 522286 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([C:38]([OH:40])=O)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].Cl.[CH3:42][N:43]1[C:47]2[N:48]=[C:49]([C:70]#[N:71])[N:50]=[C:51]([C:52]3[CH:53]=[N:54][C:55]([O:62][CH2:63][CH:64]4[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]4)=[C:56]([C:58]([F:61])([F:60])[F:59])[CH:57]=3)[C:46]=2[CH:45]=[CH:44]1.C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[C:70]([C:49]1[N:50]=[C:51]([C:52]2[CH:57]=[C:56]([C:58]([F:59])([F:60])[F:61])[C:55]([O:62][CH2:63][CH:64]3[CH2:69][CH2:68][N:67]([C:38]([CH:35]4[CH2:34][CH2:33][N:32]([C:30]([O:29][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:31])[CH2:37][CH2:36]4)=[O:40])[CH2:66][CH2:65]3)=[N:54][CH:53]=2)[C:46]2[CH:45]=[CH:44][N:43]([CH3:42])[C:47]=2[N:48]=1)#[N:71]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic 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 117899622HCID 117899622, compound

Product 1

HCID 117899572HCID 117899572, compoundYield 70.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (546 mg) was added to a solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (329 mg) in DMF (10 mL) at room temperature, and the mixture was stirred at the same temperature for 15 minutes. 7-Methyl-4-[6-(piperidin-4-yl methoxy)-5-(trifluoromethyl)pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile monohydrochloride (500 mg) and N,N-diisopropylethylamine (0.38 mL) were added to the reaction mixture at room temperature, and the mixture was stirred at the same temperature overnight. After EtOAc and a saturated aqueous NaHCO3 solution were added to the reaction mixture, extraction thereof was performed using EtOAc, and the extract was washed with water and saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3:MeOH=100:0 to 96:4), whereby tert-butyl 4-{[4-({[5-(2-cyano-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}methyl)piperidin-1-yl]carbonyl}piperidine-1-carboxylate (488 mg) was obtained as a solid.

Workup

  1. stirringthe mixture was stirred at the same temperature overnight
  2. washthe extract was washed with water and saturated brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (CHCl3:MeOH=100:0 to 96:4)

Sources & evidence

ORD record
ord-1ad3a8393ef24f0999807db322dd4104
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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