Triethylamine → HCID 58235139, compound

HRID 1896656Notes

Reaction equation

HRID 1896656 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]([CH:20]3[CH2:24][CH2:23][NH:22][CH2:21]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=2)=[CH:4][CH:3]=1.[O:25]1[CH:29]=[CH:28][C:27]([CH:30]=O)=[N:26]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]([CH:20]3[CH2:24][CH2:23][N:22]([CH2:30][C:27]4[CH:28]=[CH:29][O:25][N:26]=4)[CH2:21]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 183730781,2-Oxazole-3-carbaldehydeHCID 57461721HCID 57461721, compound

Product 1

HCID 58235139HCID 58235139, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-[4(4-fluorophenyl)-1-pyrrolidin-3-yl-1H-imidazol-5-yl]pyrimidin-2-amine (C18) (300 mg, 0.925 mmol) and isoxazole-3-carbaldehyde (90 mg, 0.93 mmol) in toluene (5 mL) was added triethylamine (0.5 mL, 3.6 mmol), and the mixture was heated at 80° C. for 16 hours. After cooling to room temperature, the reaction was treated with sodium triacetoxyborohydride (500 mg, 2.36 mmol) and stirred for an additional 3 hours at 80° C. Solvents were removed in vacuo, and the residue was partitioned between ethyl acetate (20 mL) and water (20 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by preparative thin layer chromatography on silica gel (Eluant: ethyl acetate) provided the product as a solid. Yield: 60 mg, 0.15 mmol, 16%. LCMS m/z 406.6 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.10 (m, 1H), 2.50-2.59 (m, 2H), 2.84 (dd, J=10.5, 6.7 Hz, 1H), 3.09 (dd, J=10.4, 2.4 Hz, 1H), 3.16 (m, 1H), 3.85 (AB quartet, JAB=14.0 Hz, ΔνAB=23.1 Hz, 2H), 5.29 (m, 1H), 6.40 (d, J=4.9 Hz, 1H), 6.55 (br s, 1H), 7.07 (dd, J=8.7, 8.7 Hz, 2H), 7.41 (dd, J=8.5, 5.5 Hz, 2H), 8.12 (d, J=5.2 Hz, 1H), 8.21 (s, 1H), 8.63 (br s, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customSolvents were removed in vacuo
  3. customthe residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by preparative thin layer chromatography on silica gel (Eluant: ethyl acetate)

Sources & evidence

ORD record
ord-847afe179175455daecd2ab038fa441e
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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