Sodium Carbonate → Ethyl 3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoate

HRID 1482883Notes

Reaction equation

HRID 1482883 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:15]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[CH:13]=[CH:12][N:11]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.[CH2:19]([O:21][C:22](=[O:34])[CH2:23][CH2:24][C:25]1[N:30]=[CH:29][C:28](B(O)O)=[CH:27][N:26]=1)[CH3:20].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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].C(Cl)Cl>[CH:16]1([C:14]2[CH:13]=[CH:12][N:11]=[C:10]([NH:9][C:4]3[CH:3]=[C:2]([C:28]4[CH:29]=[N:30][C:25]([CH2:24][CH2:23][C:22]([O:21][CH2:19][CH3:20])=[O:34])=[N:26][CH:27]=4)[CH:7]=[C:6]([CH3:8])[CH:5]=3)[N:15]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 118103319N-(3-bromo-5-methylphenyl)-4-cyclopropyl-2-pyrimidinamineHCID 123667257[2-(3-Ethoxy-3-oxopropyl)pyrimidin-5-yl]boronic acid

Product 1

HCID 72709450Ethyl 3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

PdCl2(dppf)-CH2Cl2 adduct (0.012 g, 0.015 mmol), N-(3-bromo-5-methylphenyl)-4-cyclopropylpyrimidin-2-amine (0.036 g, 0.120 mmol), [2-(3-ethoxy-3-oxopropyl)pyrimidin-5-yl]boronic acid (0.022 g, 0.1 mmol), and sodium carbonate (100 μL, 0.200 mmol) were suspended in dioxane (750 uL) and heated to 100° C. for 14 hours. Si-dimercaptotriazine (0.185 g, 0.1 mmol) was added to the reaction mixture. The vessel was sealed and allowed to stir at room temperature for 4 hours. The mixture was filtered, washing with DMSO (1 mL) and concentrated under reduced pressure at 40° C. The residue, dissolved in 2 mL of DMSO, was purified by mass triggered reverse phase HPLC to afford ethyl 3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoate. MS ESI calcd. For C23H26N5O2 [M+H]+ 404. found 404. 1H NMR (600 MHz, DMSO-d6) δ 9.46 (s, 1H), 8.92 (s, 2H), 8.24 (d, J=5.0 Hz, 1H), 7.96 (s, 1H), 7.55 (s, 1H), 7.10 (s, 1H), 6.78 (d, J=5.1 Hz, 1H), 4.01 (q, J=7.1 Hz, 2H), 3.18 (t, J=7.0 Hz, 2H), 2.82 (t, J=7.0 Hz, 2H), 2.31 (s, 3H), 1.99 (m, 1H), 1.12 (t, J=7.1 Hz, 3H), 1.06-0.96 (m, 4H).

Workup

  1. customThe vessel was sealed
  2. filtrationThe mixture was filtered
  3. washwashing with DMSO (1 mL)
  4. concentrationconcentrated under reduced pressure at 40° C
  5. dissolutionThe residue, dissolved in 2 mL of DMSO
  6. customwas purified by mass triggered reverse phase HPLC

Sources & evidence

ORD record
ord-39ddad3a9fdf400693b062de2590ae43
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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