[1-(tert-Butoxycarbonyl)piperidin-4-yl]acetic acid → tert-butyl 4-((4-(2-(3-isopropylphenylamino)-1-methyl-1H-benzo[d]imidazol-5-yloxy)pyridin-2-ylcarbamoyl)methyl)piperidine-1-carboxylate

HRID 1963730Notes

Reaction equation

HRID 1963730 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]([OH:17])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][C:43]1[CH:48]=[C:47]([O:49][C:50]2[CH:69]=[CH:68][C:53]3[N:54]([CH3:67])[C:55]([NH:57][C:58]4[CH:63]=[CH:62][CH:61]=[C:60]([CH:64]([CH3:66])[CH3:65])[CH:59]=4)=[N:56][C:52]=3[CH:51]=2)[CH:46]=[CH:45][N:44]=1>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH:64]([C:60]1[CH:59]=[C:58]([NH:57][C:55]2[N:54]([CH3:67])[C:53]3[CH:68]=[CH:69][C:50]([O:49][C:47]4[CH:46]=[CH:45][N:44]=[C:43]([NH:42][C:15]([CH2:14][CH:11]5[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]5)=[O:17])[CH:48]=4)=[CH:51][C:52]=3[N:56]=2)[CH:63]=[CH:62][CH:61]=1)([CH3:66])[CH3:65]

Participants

6

Reactant 3

HCID 1512539[1-(tert-Butoxycarbonyl)piperidin-4-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 690065885-(2-aminopyridin-4-yloxy)-N-(3-isopropylphenyl)-1-methyl-1H-benzo[d]imidazol-2-amine

Product 1

HCID 69006584tert-butyl 4-((4-(2-(3-isopropylphenylamino)-1-methyl-1H-benzo[d]imidazol-5-yloxy)pyridin-2-ylcarbamoyl)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid (1 eq) in N,N-dimethyl formamide and N,N,disopropylethylamine (4 eq) was added HATU (2 eq) and the mixture was stirred at ambient temperature until it becomes homogeneous. To it was added 5-(2-aminopyridin-4-yloxy)-N-(3-isopropylphenyl)-1-methyl-1H-benzo[d]imidazol-2-amine (1 eq) and 4-(dimethylamino)pyridine (0.05 eq) and the resulting mixture was stirred at room temperature for 16 h. The reaction mixture was then concentrated and partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate and the resulting tert-butyl 4-((4-(4-(methylamino)-3-nitrophenoxy)pyridin-2-ylcarbamoyl)methyl)piperidine-1-carboxylate was purified by HPLC. HPLC=4.63 min; MS: MH+=599.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 16 h
  2. concentrationThe reaction mixture was then concentrated
  3. custompartitioned between ethyl acetate and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe resulting tert-butyl 4-((4-(4-(methylamino)-3-nitrophenoxy)pyridin-2-ylcarbamoyl)methyl)piperidine-1-carboxylate was purified by HPLC
  6. customHPLC=4.63 min

Sources & evidence

ORD record
ord-16ad94847515430391c83aa47a3fcfb0
Source dataset
uspto-grants-2013_04
Patent number
US08415382B2

Reaction notes

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