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

HRID 79175

Reaction equation

HRID 79175 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][CH:30]1[CH2:35][CH2:34][N:33]([C:36]2[CH:37]=[CH:38][C:39](Cl)=[N:40][CH:41]=2)[CH2:32][CH2:31]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][CH:30]1[CH2:31][CH2:32][N:33]([C:36]2[CH:37]=[CH:38][C:39]([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:40][CH:41]=2)[CH2:34][CH2:35]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 582995615-(4-((t-Butyldimethylsilyloxy)methyl)piperidin-1-yl)-2-chloropyridineHCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 58300053N-(5-(4-(((tert-Butyl(dimethyl)silyl)oxy)methyl)-1-piperidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 57%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A 10 mL reaction vessel was charged with compound 245 (100 mg, 369 μmol), compound 281 (126 mg, 369 μmol), tris(dibenzylideneacetone)dipalladium (0) (25.3 mg, 27.6 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (32.0 mg, 55.3 μmol), sodium t-butoxide (70.8 mg, 737 μmol), and dioxane (1.5 mL).). The reaction was purged with argon and heated with microwave energy (300 W) for 2 hours at 120° C. The resulting solution was added to 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/0-35% ethyl acetate+2.5% TEA) afforded compound 282 as a yellow solid (121 mg, 57%).

Workup

  1. customA 10 mL reaction vessel
  2. customThe reaction was purged with argon
  3. additionThe resulting solution was added to ethyl acetate (40 mL)
  4. washwashed with water (30 mL) and brine (30 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. customevaporated
  7. customto give an orange oil
  8. washSilica gel chromatography (gradient elution hexanes+2.5% TEA/0-35% ethyl acetate+2.5% TEA)

Sources & evidence

ORD record
ord-3f369aaf6b404f96a26ee9bc8aa68b06
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Linked notes

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