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

HRID 79153Notes

Reaction equation

HRID 79153 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[Na+].Cl[C:50]1[N:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][N:59]([CH2:62][CH2:63][O:64][Si:65]([C:68]([CH3:71])([CH3:70])[CH3:69])([CH3:67])[CH3:66])[CH2:58][CH2:57]2)=[CH:52][CH:51]=1.[CH:72]1([N:77]2[C:81]3[N:82]=[C:83]([NH2:86])[N:84]=[CH:85][C:80]=3[C:79]3[CH:87]=[CH:88][N:89]=[C:90]([F:91])[C:78]2=3)[CH2:76][CH2:75][CH2:74][CH2:73]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:72]1([N:77]2[C:81]3[N:82]=[C:83]([NH:86][C:50]4[CH:51]=[CH:52][C:53]([N:56]5[CH2:61][CH2:60][N:59]([CH2:62][CH2:63][O:64][Si:65]([C:68]([CH3:71])([CH3:70])[CH3:69])([CH3:67])[CH3:66])[CH2:58][CH2:57]5)=[CH:54][N:55]=4)[N:84]=[CH:85][C:80]=3[C:79]3[CH:87]=[CH:88][N:89]=[C:90]([F:91])[C:78]2=3)[CH2:73][CH2:74][CH2:75][CH2:76]1

Participants

6

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 582997451-(6-Chloro-3-pyridinyl)-4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-piperazine

Product 1

HCID 582997739-Cyclopentyl-N-(5-(4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineYield 48.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
105 °C

Procedure

To tris(dibenzylideneacetone)dipalladium (0) (0.0289 g, 0.0316 mmol), xantphos (0.0366 g, 0.0632 mmol), NaOtBu (0.0486 g, 0.506 mmol), compound 247 (0.150 g, 0.421 mmol), and compound 245 (0.114 g, 0.421 mmol) was added degassed dioxane (2.0 mL). The reaction vessel was sealed and stirred at 105° C. overnight. The reaction was loaded directly to silica. Silica gel chromatography (gradient elution 1.5 to 5% 2 M methanolic NH3 in DCM) afforded compound 248 (0.120 g, 48.2% yield). 1H NMR (400 MHz, CDCl3) δ 0.09 (s, 6 H) 0.83-1.00 (m, 9 H) 1.75-1.90 (m, 2 H) 2.05-2.25 (m, 4 H) 2.36-2.53 (m, 2 H) 2.63 (br. s., 2 H) 2.75 (br. s., 4 H) 3.22 (br. s., 4 H) 3.82 (br. s., 2 H) 5.54 (quin, J=9.00 Hz, 1 H) 7.38 (dd, J=9.00, 2.74 Hz, 1 H) 7.72 (dd, J=5.09, 3.13 Hz, 1H) 8.00-8.04 (m, 1 H) 8.06 (d, J=2.74 Hz, 1 H) 8.10 (s, 1 H) 8.36 (d, J=9.00 Hz, 1 H) 9.08 (s, 1 H) ppm.

Workup

  1. customdegassed dioxane (2.0 mL)
  2. customThe reaction vessel was sealed
  3. washSilica gel chromatography (gradient elution 1.5 to 5% 2 M methanolic NH3 in DCM)

Sources & evidence

ORD record
ord-25b5158dd4cd4b8cbfb106d1314fab01
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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