Triethylamine → HCID 57881228, compound

HRID 1817712Notes

Reaction equation

HRID 1817712 reaction equation
C(O[C:4]([C:6]1[C:7]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)=[N:8][C:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[N:10][CH:11]=1)=O)C.C(OC(=O)C(C(=O)C1C=CC(C)=CC=1)=[CH:32][N:33](C)[CH3:34])C.Cl.FC1C=CC(CC(N)=N)=CC=1.CCN(CC)CC>CCO.O>[F:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][C:9]2[N:8]=[C:7]([C:20]3[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=3)[C:6]([CH2:4][N:33]([CH3:34])[CH3:32])=[CH:11][N:10]=2)=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 17221602(4-Fluorophenyl)ethanimidamide--hydrogen chloride (1/1)HCID 66616382HCID 66616382, compoundHCID 66616462HCID 66616462, compound

Product 1

HCID 57881228HCID 57881228, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

2-(4-Fluoro-benzyl)-4-p-tolyl-pyrimidine-5-carboxylic acid ethyl ester. To solution of 3-dimethylamino-2-(4-methyl-benzoyl)-acrylic acid ethyl ester (Tetrahedron, 2002, 58, 8581-8589; 0.567 g, 2.15 mmol) in EtOH (10 mL) was added 2-(4-fluoro-phenyl)-acetamidine hydrochloride (0.405 g, 2.15 mmol) and Et3N (0.90 mL, 6.5 mmol). The mixture was heated at reflux for 18 h, and then was diluted with water and extracted with EtOAc (2×). The combined organic layers were dried and concentrated. The resulting residue was purified via SiO2 chromatography (5-20% EtOAc/hexanes) to give 0.560 g (74%) of the title compound. MS (ESI): exact mass calcd. for C21H19FN2O2, 350.14; m/z found, 351.4 [M+H]+. 1H NMR (CDCl3): 8.97 (s, 1H), 7.51 (d, J=8.2, 2H), 7.38-7.35 (m, 2H), 7.27-7.26 (m, 2H), 7.01-6.97 (m, 2H), 4.32 (s, 2H), 4.23 (q, J=7.1, 2H), 2.42 (s, 3H), 1.16 (t, J=7.1, 3H). Step B. [2-(4-Fluoro-benzyl)-4-p-tolyl-pyrimidin-5-yl]-methanol. To a 0° C. solution of the product from Step A (0.606 g, 1.73 mmol) in THF (8 mL) was added DIBAL-H (1.5 M in toluene; 2.5 mL, 3.8 mmol). The mixture was allowed to warm to rt, and was stirred for 18 h. The mixture was diluted with 20% aq. sodium potassium tartrate and extracted with EtOAc (2×). The combined organic layers were dried and concentrated. The resulting residue was purified via SiO2 chromatography (40-60% EtOAc/hexanes) to give 0.330 g (62%) of the title compound. MS (ESI): exact mass calcd. for C19H17FN2O, 308.13; m/z found, 309.4 [M+H]+. 1H NMR (CDCl3): 8.77 (s, 1H), 7.58 (d, J=8.0, 2H), 7.38-7.35 (m, 2H), 7.29 (d, J=7.9, 2H), 6.99-6.96 (m, 2H), 4.70 (s, 2H), 4.29 (s, 2H), 2.42 (s, 3H). Step C. The title compound was prepared using the methods described in Example 112, Step C. MS (ESI): exact mass calcd. for C21H22FN3, 335.18; m/z found, 336.4 [M+H]+. 1H NMR (CDCl3): 8.67 (s, 1H), 7.69 (d, J=8.1, 2H), 7.40-7.36 (m, 2H), 7.29 (d, J=7.9, 2H), 7.01-6.96 (m, 2H), 4.29 (s, 2H), 3.36 (s, 2H), 2.42 (s, 3H), 2.22 (s, 6H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 18 h
  3. extractionextracted with EtOAc (2×)
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. customThe resulting residue was purified via SiO2 chromatography (5-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7b2f2fa4170543d898b72245a1a00787
Source dataset
uspto-grants-2009_10
Patent number
US07598255B2

Reaction notes

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