Diisopropylethylamine → HCID 59490687, compound

HRID 2383442Notes

Reaction equation

HRID 2383442 reaction equation
[CH:1]1[C:13]2[C:12]3[CH2:11][CH2:10][N:9]([C:14]([NH:16][C:17]4[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=4)[C:20]([OH:22])=O)=[O:15])[CH2:8][C:7]=3[CH:6]=[N:5][C:4]=2[NH:3][N:2]=1.[NH:26]1[CH2:31][CH2:30][CH:29]([N:32]2[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[NH:34][C:33]2=[O:41])[CH2:28][CH2:27]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CC(N(C)C)=O.CCOC(C)=O>[O:41]=[C:33]1[N:32]([CH:29]2[CH2:28][CH2:27][N:26]([C:20]([C:19]3[CH:18]=[C:17]([NH:16][C:14]([N:9]4[CH2:8][C:7]5[CH:6]=[N:5][C:4]6[NH:3][N:2]=[CH:1][C:13]=6[C:12]=5[CH2:11][CH2:10]4)=[O:15])[CH:25]=[CH:24][CH:23]=3)=[O:22])[CH2:31][CH2:30]2)[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[NH:34]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59490683HCID 59490683, compound

Product 1

HCID 59490687HCID 59490687, compoundYield 27.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-(6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7-carboxamido)benzoic acid (0.080 g, 0.24 mmol) and 1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one (0.057 g, 0.264 mmol) in dimethylacetamide (5 mL) and Hunig's Base (0.124 mL, 0.71 mmol) was added HBTU (0.107 g, 0.284 mmol). The reaction mixture was vortexed and then shaken at room temperature for 2 hours. On completion of the reaction, 1M NaHCO3 (20 mL) and EtOAc (30 mL) were added to the reaction mixture. The organic layer was separated, washed with brine (2×20 mL) and concentrated under reduced pressure to give a white solid. The white solid was washed with EtOAc and dried under reduced pressure to give the desired product, N-(3-(4-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carbonyl)phenyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxamide (0.035 g, 27%) as a white solid. Alternatively, the crude product can be purified either by flash column chromatography (SiO2) or reverse phase HPLC (using TFA as a modifier). White solid; M.p.=>215° C.; 400 MHz 1H NMR (DMSO-d6) δ: 13.59 (s, 1H), 10.88 (s, 1H), 8.9 (s, 1H), 8.35 (s, 1H), 8.17 (s, 1H), 7.64-7.56 (m, 2H), 7.38-7.26 (m, 2H), 7.08-6.94 (m, 4H), 4.79 (s, 2H), 4.65 (br s, 1H), 4.52-4.4 (m, 1H), 3.84 (t, J=6 Hz, 2H), 3.85-3.7 (m, 1H), 3.4-3.3 (m, 1H), 3.2-3.1 (m, 2H), 3.0-2.85 (m, 1H), 2.4-2.2 (m, 2H), 1.9-1.6 (m, 2H); LCMS [M+H]: 537.

Workup

  1. additionwere added to the reaction mixture
  2. customThe organic layer was separated
  3. washwashed with brine (2×20 mL)
  4. concentrationconcentrated under reduced pressure
  5. customto give a white solid
  6. washThe white solid was washed with EtOAc
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-e92ad6f8417147a5b8f9d0e38660a246
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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