Diisopropylethylamine → HCID 86614827, compound

HRID 2039717Notes

Reaction equation

HRID 2039717 reaction equation
[C:1]1([C:7]2[N:12]=[C:11]([Cl:13])[N:10]=[C:9](Cl)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:15][C@@H:16]([CH3:25])[C:17]([NH:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[O:18].C(N(C(C)C)CC)(C)C>C(O)(C)C>[Cl:13][C:11]1[N:10]=[C:9]([NH:15][CH:16]([CH3:25])[C:17]([NH:19][CH2:20][C:21]([F:22])([F:23])[F:24])=[O:18])[CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2415542,4-Dichloro-6-phenylpyrimidineHCID 28172283(S)-2-amino-N-(2,2,2-trifluoroethyl)propanamide

Product 1

HCID 86614827HCID 86614827, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

As shown in FIG. 3—step i, a mixture of phenylboronic acid (1.22 g), 2,4,6-trichloropyrimidine (compound 1011), tetrakis(triphenylphosphine) palladium(0) and 2N sodium carbonate (15 mL) in DME (25 mL) was heated at 80° C. overnight. After cooling to rt, addition of water (30 mL), extraction with dichloromethane (3×20 mL), drying and evaporation, purification by column chromatography (SiO2, 10-20% ethyl acetate in hexane) afforded the desired product, 6-phenyl-2,4-dichloropyrimidine (compound 1012) (0.544 g). As shown in FIG. 3—step ii, compound 1012 (0.34 g) was mixed with (S)-2-amino-N-(2,2,2-trifluoroethyl)propanamide (0.3 g) and diisopropylethylamine (0.63 mL) in isopropanol (5 mL) and the reaction mixture heated at 80° C. overnight. Evaporation gave a residue, which after aqueous workup and purification (SiO2, 20% ethyl acetate/hexane) produced 2-(2-chloro-6-phenyl-pyrimidin-4-ylamino)-N-(2,2,2-trifluoro-ethyl)propionamide (compound 1013) (0.165 g). As shown in FIG. 3—step iii, compound 1013 (29 mg), 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 1005), PdCl2dppf2 (7 mg), and potassium phosphate (32 mg) were heated in 1,4-dioxane (2 mL) at 80° C. overnight. To the reaction was added aqueous lithium hydroxide solution (2 mL). After heating at 60° C. for 1 h, water (20 mL) was added. Extraction with dichloromethane (3×), drying, evaporation and purification (SiO2, 50-100% ethyl acetate/hexane) gave 3.7 mg of 2-[6-phenyl-2-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-pyrimidin-4-ylamino]-N-(2,2,2-trifluoro-ethyl)-propionamide (compound 18).

Workup

  1. customEvaporation
  2. customgave a residue, which
  3. customafter aqueous workup and purification (SiO2, 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-78fbf188196446459623314d98ac736a
Source dataset
uspto-grants-2013_11
Patent number
US08580802B2

Reaction notes

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