Dimethylformamide → (E)-Ethyl 3-(2-amino-4-(ethylamino)-6-methylpyrimidin-5-yl)acrylate

HRID 1666257Notes

Reaction equation

HRID 1666257 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[C:7](I)[CH:6]=[C:5]([NH:10][CH2:11][CH3:12])[N:4]=1.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[CH:14]=[CH2:15].[CH2:20](N(CC)CC)C.CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)=O>[NH2:2][C:3]1[N:4]=[C:5]([NH:10][CH2:11][CH3:12])[C:6](/[CH:15]=[CH:14]/[C:13]([O:17][CH2:18][CH3:19])=[O:16])=[C:7]([CH3:20])[N:8]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 866284152-Amino-6-ethylamino-4-iodopyrimidine hydrochloride

Product 1

HCID 57606983(E)-Ethyl 3-(2-amino-4-(ethylamino)-6-methylpyrimidin-5-yl)acrylateYield 67%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 180AcetoneSolvent

Conditions

Temperature
95 °C

Procedure

To a three-neck round bottom flask equipped with over-head mechanic stirrer were added 2-amino-6-ethylamino-4-iodopyrimidine hydrochloride (188.5 g, 0.60 mol), ethyl acrylate (221 mL, 2.0 mol), triethylamine (285 mL, 2.0 mol), DMF (1.3 L), and tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 31.3 g, 0.027 mol). The reaction mixture was heated to 95° C. and stirred for 3 h (monitored by LC/MC). After reaction completion, the reaction mixture was evaporated about to 1/10 of original volume and partitioned with 500 mL of ethyl acetate and 1000 mL of water. The aqueous layer was extracted with ethyl acetate 5 times. (E)-Ethyl 3-(2-amino-4-(ethylamino)-6-methylpyrimidin-5-yl)acrylate (100 g, 67% yield) was obtained by recrystallization from acetone after evaporation of ethyl acetate. 1H NMR (400 MHz, CD3OD) δ 7.48 (dd, J1=16.0 Hz, J2=4.0 Hz, 1H), 6.20 (dd, J1=16 Hz, J2=4 Hz, 1H), 4.25 (q, J=7.2 Hz, 2H), 3.51 (q, J=7.6 Hz, 2H), 2.39 (s, 3H), 1.3 (t, J=7.2 Hz, 3H), 1.2 (t, J=7.6 Hz, 3H). MS (EI) for C12H18N4O2: 251.3 (MH+).

Workup

  1. customTo a three-neck round bottom flask equipped with over-head mechanic stirrer
  2. customAfter reaction completion
  3. customthe reaction mixture was evaporated about to 1/10 of original volume
  4. custompartitioned with 500 mL of ethyl acetate and 1000 mL of water
  5. extractionThe aqueous layer was extracted with ethyl acetate 5 times

Sources & evidence

ORD record
ord-f84bae5f40f740e6bc71c465d8edab4b
Source dataset
uspto-grants-2011_10
Patent number
US08044062B2

Reaction notes

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