Sodium Carbonate → HCID 86699658, compound

HRID 929543Notes

Reaction equation

HRID 929543 reaction equation
Br[C:2](=[CH2:18])[CH2:3][NH:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:8]=[CH:7][N:6]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][N:30]=[C:29]3[O:33][CH2:34][CH2:35][O:36][C:28]=23)O1.C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:36]1[C:28]2[C:29](=[N:30][CH:31]=[CH:32][C:27]=2[C:2](=[CH2:18])[CH2:3][NH:4][C:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][C:14]([CH3:17])=[CH:15][CH:16]=3)[N:8]=[CH:7][N:6]=2)[O:33][CH2:34][CH2:35]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49761555HCID 49761555, compoundHCID 86699659HCID 86699659, compound2×

Product 1

HCID 86699658HCID 86699658, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

As shown in step 8-i of Scheme 8, N-(2-bromoallyl)-6-(6-methyl-3-pyridyl)pyrimidin-4-amine (240 mg, 0.7792 mmol, Compound 2027; which was prepared by reacting 4-chloro-6-(6-methylpyridin-3-yl)pyrimidine with 2-bromoprop-2-en-1-amine under basic conditions), 8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (287.0 mg, 1.091 mmol), and Na2CO3 (1.169 mL of 2 M, 2.338 mmol) were stirred in DMSO (5.945 mL). Pd(dppf)Cl2 (63.63 mg, 0.07792 mmol) was added and the reaction mixture stirred at 100° C. for 1 hour, then at RT for 16 hours. After this time the reaction mixture was partitioned between EtOAc and water, the organics dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The residue was dissolved in DCM and purified by medium pressure silica gel chromatography (20-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to produce N-(2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl)allyl)-6-(6-methylpyridin-3-yl)pyrimidin-4-amine (Compound 2028) as yellow oil: LCMS=362.37 (M+H). This material was used as is in subsequent reactions.

Workup

  1. waitat RT for 16 hours
  2. customAfter this time the reaction mixture was partitioned between EtOAc and water
  3. dry with materialthe organics dried over Na2SO4
  4. filtrationfiltered
  5. customthe volatiles removed under reduced pressure
  6. dissolutionThe residue was dissolved in DCM
  7. custompurified by medium pressure silica gel chromatography (20-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-b2f5a0c4d1114db6b4e2e255098df124
Source dataset
uspto-grants-2016_03
Patent number
US09296701B2

Reaction notes

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