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 1487631Notes

Reaction equation

HRID 1487631 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% (hexane:ethyl acetate—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, 1H), 8.20 (dd, J=7.81, 1.56 Hz, 1H), 8.07 (dd, J=16.59, 8.39 Hz, 2H), 7.22-7.31 (m, 3H), 5.49 (s, 1H), 3.78-3.88 (m, 2H), 3.52-3.61 (m, 2H), 3.07 (s, 6H), 2.96 (s, 3H), 2.35 (s, 3H), 2.08 (d, J=13.28 Hz, 2H), 1.73-1.84 (m, 2H). MS (ESI) m/z 530.0 [M+1]+.

Workup

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

Sources & evidence

ORD record
ord-01ecd6fb67124e8dabfa741df4d55d45
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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