1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 9-Cyclopentyl-2-((5-((3R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3',2':4,5]pyrrolo[2,3-d]-pyrimidin-7-one

HRID 79168Notes

Reaction equation

HRID 79168 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]3[CH:11]=[CH:12][C:13](=[O:16])[N:14]([CH3:15])[C:9]=3[N:8]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:7]=1.[Si:22]([O:29][C@@H:30]1[CH2:34][CH2:33][N:32]([C:35]2[CH:36]=[CH:37][C:38](Cl)=[N:39][CH:40]=2)[CH2:31]1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].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+]>O1CCOCC1.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:17]1([N:8]2[C:6]3[N:7]=[C:2]([NH:1][C:38]4[CH:37]=[CH:36][C:35]([N:32]5[CH2:33][CH2:34][C@@H:30]([O:29][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:23])[CH3:24])[CH2:31]5)=[CH:40][N:39]=4)[N:3]=[CH:4][C:5]=3[C:10]3[CH:11]=[CH:12][C:13](=[O:16])[N:14]([CH3:15])[C:9]2=3)[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 582996662-Amino-9-cyclopentyl-8-methyl-8,9-dihydro-7H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-7-oneHCID 58300125(R)-5-(3-(t-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-chloropyridine

Product 1

HCID 582996139-Cyclopentyl-2-((5-((3R)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-pyridinyl)amino)-8-methyl-8,9-dihydro-7H-pyrido[3',2':4,5]pyrrolo[2,3-d]-pyrimidin-7-oneYield 49.1%

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 273 (55 mg, 193 μmol), (R)-5-(3-(t-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-chloropyridine (60.3 mg, 193 μmol), tris(dibenzylideneacetone)dipalladium (0) (13 mg, 14 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (17 mg, 29 μmol), and sodium t-butoxide (22 mg, 231 μmol) in 2 mL dry dioxane. The reaction was purged with argon and heated with microwave energy (300 W) for 2 hours at 120° C. The resulting solution was taken up in ethyl acetate (40 mL) and washed with water (30 mL), and brine (30 mL). The organics were dried (MgSO4) and evaporated to give a brown oil. Silica gel chromatography (gradient elution hexanes+2.5% TEA/0-50% ethyl acetate+2.5% TEA) afforded compound 276 as a yellow solid (53 mg, 49%).

Workup

  1. customA 10 mL reaction vessel
  2. customThe reaction was purged with argon
  3. washwashed with water (30 mL), and brine (30 mL)
  4. dry with materialThe organics were dried (MgSO4)
  5. customevaporated
  6. customto give a brown oil
  7. washSilica gel chromatography (gradient elution hexanes+2.5% TEA/0-50% ethyl acetate+2.5% TEA)

Sources & evidence

ORD record
ord-05df39bfa42348d2a520125b17e2d831
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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