Cesium carbonate → 1-((6-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)methyl)-4-piperidinol

HRID 79203

Reaction equation

HRID 79203 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][CH:31]([OH:34])[CH2:30][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[CH2:29][CH2:30][CH:31]([OH:34])[CH2:32][CH2:33]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 201146451-((6-Chloropyridin-3-yl)methyl)piperidin-4-olHCID 582995859-Cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 582996531-((6-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)methyl)-4-piperidinolYield 14.3%

Reagents, catalysts & solvents 2

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

Procedure

In a 10 mL microwave reaction vessel were placed compound 4 (40 mg, 158 μmol), 1-(6-chloro-pyridin-3-ylmethyl)piperidin-4-ol (36 mg, 158 μmol), tris(dibenzylideneacetone)dipalladium (0) (7.2 mg, 7.9 μmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (11 mg, 20 μmol), and cesium carbonate (25 μl, 316 μmol) followed by 1,4-dioxane (3 mL). The vessel was purged with N2 for 5 min, then capped and subjected to microwave condition (1.5 h at 120° C.). After the volatiles were removed, the residue was purified by combi-flash column chromatography followed by reverse phase preparative HPLC (acetonitrile/H2O containing 0.1% TFA each, 40 min from 10 to 40%). Lyophilization provided compound 342 (10 mg) as an off-white solid (TFA salt). 1H NMR (500 MHz, DMSO-d6) δ ppm 10.00 (1 H, s), 9.32 (1 H, s), 9.03 (1 H, s), 8.46 (1 H, d, J=5.1 Hz), 8.32 (1 H, d, J=8.3 Hz), 8.19 (1 H, d, J=1.7 Hz), 8.04-8.10 (1 H, m), 7.72 (1 H, dd, J=8.6, 2.0 Hz), 5.39 (1 H, quin, J=8.8 Hz), 4.54 (1 H, d, J=3.9 Hz), 3.43 (3 H, s), 2.64-2.72 (2 H, m), 2.37-2.45 (2 H, m), 2.00-2.17 (6 H, m), 1.65-1.84 (4 H, m), 1.39 (2 H, t, J=9.9 Hz). LCMS-ESI (POS), M/Z, M+1: Found 444.2.

Workup

  1. customIn a 10 mL microwave reaction vessel were placed
  2. customThe vessel was purged with N2 for 5 min
  3. customcapped
  4. customsubjected to microwave condition (1.5 h at 120° C.)
  5. customAfter the volatiles were removed
  6. customthe residue was purified by combi-flash column chromatography
  7. custom40 min

Sources & evidence

ORD record
ord-9831dde4afd54c94b685905451dac0fe
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Linked notes

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