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

HRID 875997Notes

Reaction equation

HRID 875997 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][C@@H:29]1[CH2:33][CH2:32][N:31]([C:34]2[CH:35]=[CH:36][C:37](Cl)=[N:38][CH:39]=2)[CH2:30]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].C(OCC)(=O)C.O1CCOCC1>[Si:21]([O:28][C@@H:29]1[CH2:33][CH2:32][N:31]([C:34]2[CH:35]=[CH:36][C:37]([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:38][CH:39]=2)[CH2:30]1)([C:24]([CH3:27])([CH3:25])[CH3:26])([CH3:23])[CH3:22]

Participants

8

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 58300125(R)-5-(3-(t-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-chloropyridine

Product 1

HCID 58299699N-(5-((3R)-3-((tert-butyl(dimethyl)silyl)oxy)-1-pyrrolidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 39%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A 10 mL reaction vessel was charged with compound 245 (75.0 mg, 276 mmol), (R)-5-(3-(t-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-chloropyridine (86.5 mg, 276 mmol), tris(dibenzylideneacetone)dipalladium (0) (19.0 mg, 20.7 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (24.0 mg, 41.5 mmol), sodium t-butoxide (53.1 mg, 553 mmol), and dioxane (1.5 mL). The reaction was heated with microwave energy (300 W) for 2 hours at 120° C. in the resulting solution was added to ethyl acetate (40 mL) and washed with water (30 mL) followed by brine (30 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution 35% ethyl acetate in hexanes) afforded compound 278 as a yellow solid (59 mg, 39%)

Workup

  1. customA 10 mL reaction vessel
  2. washwashed with water (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 35% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-91567dd08dfa4f599b81252855dbb685
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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