Diisopropylethylamine → HCID 66977626, compound

HRID 77097Notes

Reaction equation

HRID 77097 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[C:12]([N:17]2[CH2:21][CH2:20][CH:19]([C:22](O)=[O:23])[CH2:18]2)[CH:13]=[CH:14][C:15]=1[Cl:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)=[O:64])([CH3:61])([CH3:60])[CH3:59]>>[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][N:68]([C:22]([CH:19]2[CH2:20][CH2:21][N:17]([C:12]3[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([C:2]4[NH:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)[CH:11]=3)[CH2:18]2)=[O:23])[CH2:67][CH2:66]1)=[O:64])([CH3:61])([CH3:59])[CH3:60]

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669777401-[3-(1H-Benzoimidazol-2-yl)-4-chloro-phenyl]-pyrrolidine-3-carboxylic acid

Product 1

HCID 66977626HCID 66977626, compoundYield 83%

Conditions

Temperature
35 °C

Procedure

Method G—Step a To a mixture of 1-[3-(1H-Benzoimidazol-2-yl)-4-chloro-phenyl]-pyrrolidine-3-carboxylic acid (obtained as described in general method 2, step e) (0.01 g, 0.26 mmol) in dcm (4 mL), HATU (0.10 g, 0.29 mmol), diisopropylethylamine (DIPEA) (0.14 mL, 0.76 mmol) and tert-butyl-1-piperazine carboxylate (0.06 g, 0.32 mmol) were added. The reaction mixture was heated at 35° C. overnight, cooled to room temperature and washed with water (2×5 mL) and saturated Na2CO3 solution (2×5 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure to obtain a crude that was triturated with diethylether (3 mL), filtered and dried. The precipitate was then purified by flash chromatography (eluent gradient: EtOAc 100% to EtOAc:NH3 in MeOH (2M)/4:0.8), and then a filtration on an SCX cartridge was run (eluent gradient: DCM:MeOH/1:1 to NH3 in MeOH), to obtain 0.11 g of the title compound (67%).

Workup

  1. additionwere added
  2. temperaturecooled to room temperature
  3. washwashed with water (2×5 mL) and saturated Na2CO3 solution (2×5 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto obtain a crude that
  8. customwas triturated with diethylether (3 mL)
  9. filtrationfiltered
  10. customdried
  11. customThe precipitate was then purified by flash chromatography (eluent gradient: EtOAc 100% to EtOAc:NH3 in MeOH (2M)/4:0.8)
  12. filtrationa filtration on an SCX cartridge

Sources & evidence

ORD record
ord-72d4ca0834ca4ae9be78011979c74bf5
Source dataset
uspto-grants-2014_09
Patent number
US08835648B2

Reaction notes

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