1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → tert-Butyl (2R)-2-(((tert-butyl(dimethyl)silyl)oxy)methyl)-4-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-1-piperazinecarboxylate

HRID 876014Notes

Reaction equation

HRID 876014 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][C@H:30]1[CH2:35][N:34]([C:36]2[CH:37]=[N:38][C:39](Cl)=[CH:40][CH:41]=2)[CH2:33][CH2:32][N:31]1[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])([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][C@H:30]1[CH2:35][N:34]([C:36]2[CH:37]=[N: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)=[CH:40][CH:41]=2)[CH2:33][CH2:32][N:31]1[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])([C:24]([CH3:27])([CH3:26])[CH3:25])([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 86654440(R)-t-butyl 2-((t-butyldimethylsilyloxy)methyl)-4-(6-chloropyridin-3-yl)piperazine-1-carboxylate

Product 1

HCID 68322580tert-Butyl (2R)-2-(((tert-butyl(dimethyl)silyl)oxy)methyl)-4-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-1-piperazinecarboxylateYield 69%

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 (83.0 mg, 306 μmol), compound 309 (135 mg, 306 μmol), tris(dibenzylideneacetone)dipalladium (0) (21.0 mg, 22.9 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (26.6 mg, 45.9 μmol), sodium t-butoxide (58.8 mg, 612 μmol), and dioxane (2.5 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 aqueous K2CO3 (30 mL) and extracted with dichloromethane+10% methanol (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow oil. Silica gel chromatography (gradient elution hexanes/20-100% ethyl acetate) afforded compound 310 as a colorless oil (142 mg, 69%).

Workup

  1. customA 10 mL reaction vessel
  2. customThe reaction was purged with argon
  3. additionThe resulting solution was added to aqueous K2CO3 (30 mL)
  4. extractionextracted with dichloromethane+10% methanol (3×30 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. customevaporated
  7. customto give a yellow oil
  8. washSilica gel chromatography (gradient elution hexanes/20-100% ethyl acetate)

Sources & evidence

ORD record
ord-1fc8dfb827e342b8b47add97c422ef3a
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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