Allylamine → HCID 23568905, compound

HRID 2376227Notes

Reaction equation

HRID 2376227 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:30]([O:32][C:33](=[O:62])[CH:34]([C:55]1[CH:56]=[C:57]([CH3:61])[CH:58]=[CH:59][CH:60]=1)[CH2:35][C:36]1[CH:40]=[C:39]([C:41]2[CH:46]=[CH:45][C:44](Br)=[CH:43][CH:42]=2)[N:38]([C:48]2[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=2)[N:37]=1)[CH3:31].[CH2:63]([NH2:66])[CH:64]=[CH2:65]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[CH2:30]([O:32][C:33](=[O:62])[CH:34]([C:55]1[CH:56]=[C:57]([CH3:61])[CH:58]=[CH:59][CH:60]=1)[CH2:35][C:36]1[CH:40]=[C:39]([C:41]2[CH:46]=[CH:45][C:44]([NH:66][CH2:63][CH:64]=[CH2:65])=[CH:43][CH:42]=2)[N:38]([C:48]2[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=2)[N:37]=1)[CH3:31]

Participants

8

Reactant 4

HCID 7853AllylamineHCID 62657Potassium Phosphate, TribasicHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23568904HCID 23568904, compound

Product 1

HCID 23568905HCID 23568905, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of Pd2(dibenzylideneacetone)3 (4 mg, 0.004 mmol, 1 mol %), 2-(di-tert-butylphosphino)biphenyl (6 mg, 0.02 mmol, 5 mol %) and K3PO4 (130 mg, 0.61 mmol, 1.5 equiv) was added a solution of 3-[5-(4-bromo-phenyl)-1-p-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid ethyl ester (Example 77, Step C; 200 mg, 0.4 mmol) in toluene (0.6 mL) followed by allylamine (0.030 mL, 0.48 mmol, 1.2 equiv). The resulting mixture was stirred at 110° C. for 12 h and then cooled to room temperature. Ethyl acetate (2 mL) and water (3 mL) were added, and the resulting aqueous layer was back-extracted with EtOAc (3×2 mL). The combined organic layers were washed with brine (3 mL), and then dried (MgSO4). The solvent was evaporated under reduced pressure, and the residue was purified by chromatography (silica gel, 25% ethyl acetate/hexanes) to afford the desired compound (90 mg, 47%). HPLC: Rt=3.19 (Method B). MS (ESI): mass calculated for C31H33N3O2, 479.26; m/z found, 480.3 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.29 (s, 1H), 7.27-7.04 (m, 7H), 6.96 (d, J=8.5 Hz, 2H), 6.49 (d, J=8.5 Hz, 2H), 6.07 (s, 1H), 5.96-5.89 (m, 1H), 5.29-5.25 (m, 1H), 5.18-5.16 (m, 1H), 4.20-4.14 (m, 1H), 4.10-4.02 (m, 2H), 3.76-3.75 (m, 2H), 3.52-3.45 (m, 1H), 3.08 (dd, J=14.5, 6.0 Hz, 1H), 2.34 (s, 6H), 1.19 (t, J=7.1 Hz, 1H).

Workup

  1. temperaturecooled to room temperature
  2. extractionthe resulting aqueous layer was back-extracted with EtOAc (3×2 mL)
  3. washThe combined organic layers were washed with brine (3 mL)
  4. dry with materialdried (MgSO4)
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by chromatography (silica gel, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a4ea6dee33634d838a4d40754084ad6e
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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