Dimethylformamide → tert-butyl 4-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)piperidine-1-carboxylate

HRID 1946090Notes

Reaction equation

HRID 1946090 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11](O)=O)C)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)C=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[CH3:60][N:61]1[C:69]([CH2:70][CH:71]2CCN[CH2:73][CH2:72]2)=[N:68][C:67]2[C:62]1=[N:63][C:64]([N:83]1[C:87]3[CH:88]=[CH:89][CH:90]=[CH:91][C:86]=3[N:85]=[C:84]1[CH3:92])=[N:65][C:66]=2[N:77]1[CH2:82][CH2:81][O:80][CH2:79][CH2:78]1>>[CH3:60][N:61]1[C:69]([CH2:70][CH:71]2[CH2:11][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:73][CH2:72]2)=[N:68][C:67]2[C:62]1=[N:63][C:64]([N:83]1[C:87]3[CH:88]=[CH:89][CH:90]=[CH:91][C:86]=3[N:85]=[C:84]1[CH3:92])=[N:65][C:66]=2[N:77]1[CH2:78][CH2:79][O:80][CH2:81][CH2:82]1

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 85082Tert-butoxycarbonylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 596056364-(9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-(piperidin-4-ylmethyl)-9H-purin-6-yl)morpholine

Product 1

HCID 59605471tert-butyl 4-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)piperidine-1-carboxylateYield 88.5%

Procedure

To a solution of N-(tert-Butoxycarbonyl)-L-alanine (80.0 mg, 0.423 mmol) in N,N-Dimethylformamide (5.0 mL, 0.064 mol) was added HATU (0.154 g, 0.404 mmol), 1-hydroxybenzotriazole (HOBt, 0.00839 g, 0.0621 mmol) and triethylamine (0.10 mL, 0.72 mmol). The resulting yellow solution was stirred at room temperature for 5 minutes before the addition of 4-(9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-(piperidin-4-ylmethyl)-9H-purin-6-yl)morpholine 520 (0.150 g, 0.310 mmol;). The reaction was stirred at room temperature for 2 hours. The reaction mixture was partitioned between brine and EtOAc. The organic extract was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (0-5% MeOH in DCM) to give tert-butyl 4-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)piperidine-1-carboxylate (0.15 g, 78%). LCMS m/z: 618.3 (MH+).

Workup

  1. customThe reaction mixture was partitioned between brine and EtOAc
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-238c47c13d3a403e8e41b750bb3c6223
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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