Cesium carbonate → HCID 58299871, compound

HRID 876036Notes

Reaction equation

HRID 876036 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH2:15])[N:13]=[CH:14][C:9]=3[C:8]3[CH:16]=[CH:17][N:18]=[CH:19][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:21]1[N:26]=[CH:25][C:24]([CH2:27][N:28]2[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]2)=[CH:23][CH:22]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:21]4[N:26]=[CH:25][C:24]([CH2:27][N:28]5[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]5)=[CH:23][CH:22]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:16]=[CH:17][N:18]=[CH:19][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 201122834-((6-Chloropyridin-3-yl)methyl)piperazin-2-oneHCID 582995859-Cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 58299871HCID 58299871, compoundYield 61.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

In a 10 mL microwave reaction vessel were placed compound 4 (93 mg, 367 μmol), compound 356 (83 mg, 367 μmol), tris(dibenzylideneacetone)dipalladium (0) (17 mg, 18 μmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (27 mg, 46 μmol), and cesium carbonate (359 mg, 1101 μmol) followed by 1,4-dioxane (3 mL). The vessel was purged with N2 for 5 min, then capped and subjected to microwave irradiation for 4 h at 120° C. The crude mixture was taken up in 4% methanol/DCM and subjected to combi-flash column chromatography (methanol/DCM) followed by preparative reverse phase HPLC (acetonitrile/water containing 0.1% TFA each, 40 min from 10 to 40%). Lyophilization provided compound 355 (100 mg) as an off-white solid (TFA salt). 1H NMR (500 MHz, CD3OD) δ ppm 9.67 (1 H, s), 9.34 (1 H, s), 8.69 (1 H, d), 8.66 (1 H, d), 8.48 (1 H, d, J=1.7 Hz), 8.24 (1 H, dd, J=8.8, 2.2 Hz), 8.04 (1 H, d, J=8.6 Hz), 5.48 (1 H, quin, J=8.7 Hz), 4.03 (2 H, s), 3.40-3.49 (4 H, m), 3.09 (2 H, t, J=5.3 Hz), 2.48-2.60 (2 H, m), 2.14-2.32 (4 H, m), 1.85-1.98 (2 H, m). LCMS-ESI (POS), M/Z, M+1: Found 443.2.

Workup

  1. customIn a 10 mL microwave reaction vessel were placed
  2. customThe vessel was purged with N2 for 5 min
  3. customcapped
  4. customirradiation for 4 h at 120° C
  5. custom40 min

Sources & evidence

ORD record
ord-3f4e5f647c8c4142ace65eb100c98988
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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