1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N-(5-(4-(2-((tert-butyl(dimethyl)silyl)oxy)ethyl)-1-piperidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79181Notes

Reaction equation

HRID 79181 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]=[C:19]([F:20])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Si:21]([O:28][CH2:29][CH2:30][CH:31]1[CH2:36][CH2:35][N:34]([C:37]2[CH:38]=[CH:39][C:40](Cl)=[N:41][CH:42]=2)[CH2:33][CH2:32]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>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>[Si:21]([O:28][CH2:29][CH2:30][CH:31]1[CH2:32][CH2:33][N:34]([C:37]2[CH:38]=[CH:39][C:40]([NH:15][C:12]3[N:13]=[CH:14][C:9]4[C:8]5[CH:16]=[CH:17][N:18]=[C:19]([F:20])[C:7]=5[N:6]([CH:1]5[CH2:2][CH2:3][CH2:4][CH2:5]5)[C:10]=4[N:11]=3)=[N:41][CH:42]=2)[CH2:35][CH2:36]1)([C:24]([CH3:27])([CH3:25])[CH3:26])([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineHCID 582998435-(4-(2-(t-Butyldimethylsilyloxy)ethyl)piperidin-1-yl)-2-chloropyridine

Product 1

HCID 58300008N-(5-(4-(2-((tert-butyl(dimethyl)silyl)oxy)ethyl)-1-piperidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 65%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A 10 mL microwave reaction tube was charged with compound 245 (80.0 mg, 295 μmol), 5-(4-(2-(t-butyldimethylsilyloxy)ethyl)piperidin-1-yl)-2-chloropyridine (293) (105 mg, 295 μmol), tris(dibenzylideneacetone)dipalladium (0) (20.3 mg, 22.1 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (25.6 mg, 44.2 μmol), sodium t-butoxide (56.7 mg, 590 μmol), and dioxane (3 mL). The reaction was purged with argon and heated with microwave energy (300 W) for 3.5 hours at 120° C. The reaction was taken up in ethyl acetate (40 mL) and washed with water (30 mL) and brine (30 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes+2.5% TEA/0-100% ethyl acetate+2.5% TEA) afforded compound 294 as a yellow solid (113 mg, 65%).

Workup

  1. customThe reaction was purged with argon
  2. washwashed with water (30 mL) and brine (30 mL)
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated
  5. customto give an orange oil
  6. washSilica gel chromatography (gradient elution hexanes+2.5% TEA/0-100% ethyl acetate+2.5% TEA)

Sources & evidence

ORD record
ord-67808a6ecfa14abca5f981fa8f11fd76
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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