Potassium Carbonate → (2-(4-(1-(2-fluoroethyl)azetidin-3-ylamino)-2-methoxyphenylamino)-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

HRID 574277Notes

Reaction equation

HRID 574277 reaction equation
[F:1][CH2:2][CH2:3][N:4]1[CH2:7][CH:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([O:16][CH3:17])[CH:10]=2)[CH2:5]1.[C:18]([O:24][CH2:25][N:26]1[C:30]2[N:31]=[C:32](Cl)[N:33]=[C:34]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([N+:42]([O-:44])=[O:43])[CH:37]=3)[C:29]=2[CH:28]=[CH:27]1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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].CC(O)(C)C>[C:18]([O:24][CH2:25][N:26]1[C:30]2[N:31]=[C:32]([NH:15][C:12]3[CH:13]=[CH:14][C:9]([NH:8][CH:6]4[CH2:7][N:4]([CH2:3][CH2:2][F:1])[CH2:5]4)=[CH:10][C:11]=3[O:16][CH3:17])[N:33]=[C:34]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([N+:42]([O-:44])=[O:43])[CH:37]=3)[C:29]=2[CH:28]=[CH:27]1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86709973HCID 86709973, compoundHCID 86709976(2-chloro-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

Product 1

HCID 86709975(2-(4-(1-(2-fluoroethyl)azetidin-3-ylamino)-2-methoxyphenylamino)-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalateYield 76.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of N1-(1-(2-fluoroethyl)azetidin-3-yl)-3-methoxybenzene-1,4-diamine (870 mg, 3.64 mmol) and (2-chloro-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (1.55 g, 3.83 mmol), potassium carbonate (1.35 g, 9.77 mmol), tris(dibenzylideneacetone)dipalladium (173 mg, 0.19 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (222 mg, 0.47 mmol), a magnetite, and t-BuOH (35 mL) was heated to reflux and stirred under nitrogen for 2 h. The mixture was cooled to 40-50° C. and was filtered through diatomaceous earth, washing with ethyl acetate (50 mL). The filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography (DCM/MeOH=50/1 as elution) to give the title compound (1.7 g, yield 74%, M+H+=608.3) as a light yellow solid.

Workup

  1. temperatureto reflux
  2. filtrationwas filtered through diatomaceous earth
  3. washwashing with ethyl acetate (50 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe crude material was purified by column chromatography (DCM/MeOH=50/1 as elution)

Sources & evidence

ORD record
ord-fb4d7aa28f0b49fcae336a11c7766969
Source dataset
uspto-grants-2015_05
Patent number
US09034885B2

Reaction notes

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