2-Pyridinemethanamine → HCID 67055860, compound

HRID 2036776Notes

Reaction equation

HRID 2036776 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](O)=[N:5][C:6]([C:12]1[CH:13]=[N:14][CH:15]=[N:16][CH:17]=1)=[N:7]2.C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH2:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=1>CN(C=O)C>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([NH:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=1)=[N:5][C:6]([C:12]1[CH:13]=[N:14][CH:15]=[N:16][CH:17]=1)=[N:7]2

Participants

6

Reactant 4

HCID 195092-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 178517559HCID 178517559, compound

Product 1

HCID 67055860HCID 67055860, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of 5-bromo-2-(pyrimidin-5-yl)quinazolin-4-ol (2.0 g, 6.5 mmol) in DMF (20 mL) was added diisopropylethyl amine (3.4 ml, 19 mmol) followed by PyBroP (3.7 g, 7.9 mmol). After 5 min stirring at room temperature, 2-aminomethylpyridine (1.0 mL, 9.8 mmol) was added to the reaction. Upon completion of addition, the reaction mixture was warmed to 80° C. where it stirred for 2 h (during which time reaction became a clear solution). At the conclusion of this period, the reaction mixture was quenched by the addition of cold water and then extracted into 50% ethyl acetate and hexane mixture (200 mL). The organic extracts were dried, concentrated, purified by column chromatography using ethyl acetate and hexanes as eluent to yield the crude produce. The crude product was further purified by trituration with ethyl acetate and hexane to yield 5-bromo-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine (0.5 g, 20% yield). 1H NMR (400 MHz, CDCl3, δ): 5.07 (d, J=4.4 Hz, 2H); 7.26 (m, 1H); 7.41 (d, J=7.6 Hz, 1H); 7.53 (t, J=8 Hz, 1H); 7.71-7.73 (m, 2H); 7.86 (dd, J=0.8 Hz, 8.4 Hz, 1H); 8.65 (d, J=4 Hz, 1H); 9.30 (s, 1H); 9.38 (br s, 1H); 9.75 (s, 2H). ES-MS: [M++1]=393 and [M++3]=395.

Workup

  1. additionUpon completion of addition
  2. temperaturethe reaction mixture was warmed to 80° C. where it
  3. stirringstirred for 2 h (
  4. customduring which time reaction
  5. customAt the conclusion of this period, the reaction mixture was quenched by the addition of cold water
  6. extractionextracted into 50% ethyl acetate and hexane mixture (200 mL)
  7. customThe organic extracts were dried
  8. concentrationconcentrated
  9. custompurified by column chromatography
  10. customto yield the crude
  11. customproduce
  12. customThe crude product was further purified by trituration with ethyl acetate and hexane

Sources & evidence

ORD record
ord-bc52321e16c641a0967bfc8b47fe167c
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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