Cesium carbonate → 5-(2-(4-(Dimethylcarbamoyl)-2-methylphenylamino)-4-(tetrahydro-2H-pyran-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide

HRID 529687Notes

Reaction equation

HRID 529687 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([C:17]([NH:19][CH3:20])=[O:18])=[N:15][CH:16]=3)=[CH:9][N:8](COCC[Si](C)(C)C)[C:6]=2[N:7]=1.[NH2:36][C:37]1[CH:47]=[CH:46][C:40]([C:41]([N:43]([CH3:45])[CH3:44])=[O:42])=[CH:39][C:38]=1[CH3:48].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>[CH3:44][N:43]([CH3:45])[C:41]([C:40]1[CH:46]=[CH:47][C:37]([NH:36][C:2]2[N:3]=[C:4]([O:29][CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:5]3[C:10]([C:11]4[CH:12]=[CH:13][C:14]([C:17]([NH:19][CH3:20])=[O:18])=[N:15][CH:16]=4)=[CH:9][NH:8][C:6]=3[N:7]=2)=[C:38]([CH3:48])[CH:39]=1)=[O:42]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 167817704-amino-N,N,3-trimethylbenzamideHCID 867264585-(2-Chloro-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide

Product 1

HCID 867264595-(2-(4-(Dimethylcarbamoyl)-2-methylphenylamino)-4-(tetrahydro-2H-pyran-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamideYield 21%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

5-(2-Chloro-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide (1 equiv), 4-amino-N,N,3-trimethylbenzamide (1 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.2 equiv), cesium carbonate (2 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv) and 1,4-dioxane (0.2 M) were combined in a microwave vial and irradiated heated at 150° C. for 30 min. The mixture was concentrated and purified by flash chromatography 0-55% (Hex:EtOAc-800 mL), followed by 5-15% B (DCM:MeOH-800 mL) in the same run. Fractions were combined, concentrated and the compound was deprotected according to General Procedure A. The reaction mixture was concentrated and purified to give the title compound (21% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.92 (d, J=1.95 Hz, 1 H), 8.20 (dd, J=7.81, 1.56 Hz, 1 H), 8.07 (dd, J=16.59, 8.39 Hz, 2 H), 7.22-7.31 (m, 3 H), 5.49 (s, 1 H), 3.78-3.88 (m, 2 H), 3.52-3.61 (m, 2 H), 3.07 (s, 6 H), 2.96 (s, 3 H), 2.35 (s, 3 H), 2.08 (d, J=13.28 Hz, 2 H), 1.73-1.84 (m, 2 H). MS (ESI) m/z 530.0 [M+1]+.

Workup

  1. customirradiated
  2. concentrationThe mixture was concentrated
  3. custompurified by flash chromatography 0-55% (Hex:EtOAc-800 mL)
  4. concentrationconcentrated
  5. concentrationThe reaction mixture was concentrated
  6. custompurified

Sources & evidence

ORD record
ord-b6c9f0a380f34b5a98ed217512b6a2ea
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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