Methylamine → 5-Iodo-N-methyl-4-pyrimidinamine

HRID 444897Notes

Reaction equation

HRID 444897 reaction equation
ClC1C(I)=CN=C[N:3]=1.CN.[I:11][C:12]1[C:13]([NH:18][CH3:19])=[N:14][CH:15]=[N:16][CH:17]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)[C:22](C)(C)[O:21]1.CC([O-])=O.[K+].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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>[I:11][C:12]1[C:13]([NH:18][CH3:19])=[N:14][CH:15]=[N:16][CH:17]=1.[CH3:22][OH:21].[NH3:3]

Participants

12

Reactant 6

HCID 6329MethylamineHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 112302044-Chloro-5-iodopyrimidineHCID 132615125-Iodo-N-methyl-4-pyrimidinamine

Product 2

HCID 132615125-Iodo-N-methyl-4-pyrimidinamineHCID 21705897Ammonia methanol

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

5-iodo-N-methylpyrimidin-4-amine (9A) was prepared from 4-chloro-5-iodopyrimidine and methylamine as described in WO2008100456. Compound 9A (37.5 mg, 0.160 mmol.) was then mixed with bis(pinacolato)diboron (46.6 mmg, 0.184 mmol), KOAc (78.3 mg, 0.798 mmol), and PdCl2(dppf) (32.6 mg, 0.040 mmol) in dioxane (2.0 mL). The mixture was heated at 105° C. overnight in a 5 mL sealed tube and then cooled to RT. The reaction was then treated with compound 5D (22.59 mg, 0.0800 mmol), K2CO3 (66.2 mg, 0.48 mmol), PdCl2(dppf) (16.3 mg, 0.020 mmol) and water (1.0 mL) and microwaved for 15 min at 125° C. The mixture was diluted with aq Na2CO3 and extracted with DCM. The organic extracts were dried over MgSO4 and concentrated. Chromatography (0-10% of (9:1 MeOH/NH3) in CH2Cl2) afforded (±)-9 (657 mg). LCMS m/z 312 (MH+).

Workup

  1. customsealed tube
  2. temperaturecooled to RT
  3. custommicrowaved for 15 min at 125° C
  4. extractionextracted with DCM
  5. dry with materialThe organic extracts were dried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-27e7e647c0c349ca980a7201249d3eda
Source dataset
uspto-grants-2013_07
Patent number
US08476274B2

Reaction notes

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