Tris(hydroxymethyl)aminomethane → HCID 11607371, compound

HRID 551904Notes

Reaction equation

HRID 551904 reaction equation
Cl.[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:34]=[CH:33][C:17]([CH2:18][NH:19][CH2:20][C:21]3[CH:32]=[CH:31][C:24]([O:25][CH2:26][C:27]([O:29]C)=[O:28])=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5].CCN(C(C)C)C(C)C.[CH:44]1([N:50]=[C:51]=[O:52])[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1.C(O)C(N)(CO)CO>C(Cl)Cl>[CH2:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]#[C:13][C:14]2[CH:15]=[CH:16][C:17]([CH2:18][N:19]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([O:25][CH2:26][C:27]([OH:29])=[O:28])=[CH:31][CH:32]=3)[C:51]([NH:50][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]3)=[O:52])=[CH:33][CH:34]=2)=[CH:10][CH:11]=1)[CH2:3][CH2:4][CH3:5]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 18502Cyclohexyl isocyanateHCID 81531DiisopropylethylamineHCID 86626584HCID 86626584, compound

Product 1

HCID 11607371HCID 11607371, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of methyl {4-[({4-[(4-butylphenyl)ethynyl]benzyl}amino)methyl]-phenoxy}acetate hydrochloride (500 mg, 1.05 mol) in anhydrous DCM (10 ml) was added DIEA (0.2 mL, 1.18 mmol) and cyclohexyl isocyanate (Aldrich, 0.28 mL, 2.20 mmol). The reaction mixture was stirred at rt for 15 hrs. Then PS-trisamine resin (670 mg, Novabiochem, 3.5 mmol/g) was added and the resulting mixture was stirred at rt for 5 additional hrs. The resin was removed by filtration, washed with DCM and the solvent was evaporated off under reduced pressure. Purification by flash chromatography on silicagel (c-Hex/EtOAc (2/1)) gave 500 mg (84%) of the title compound as a pale yellow oil. HPLC, Rt: 5.9 min (purity: 100%). LC/MS, M+(ESI): 567.4. 1H NMR (DMSO-d6) δ: 7.48 (d, J=8.3 Hz, 2H), 7.44 (d, J=8.3 Hz, 2H), 7.24 (d, J=8.3 Hz, 2H), 7.20 (d, J=8.3 Hz, 2H), 7.11 (d, J=8.6 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 6.18 (d, J=7.6 Hz, 1H), 4.76 (s, 2H), 4.37 (s, 2H), 4.31 (s, 2H), 3.68 (s, 3H), 3.48 (m, 1H), 2.60 (t, J=7.5 Hz, 2H), 1.75-1.01 (m, 14H), 0.89 (t, J=7.4 Hz, 3H).

Workup

  1. stirringthe resulting mixture was stirred at rt for 5 additional hrs
  2. customThe resin was removed by filtration
  3. washwashed with DCM
  4. customthe solvent was evaporated off under reduced pressure
  5. customPurification by flash chromatography on silicagel (c-Hex/EtOAc (2/1))

Sources & evidence

ORD record
ord-9f16337105294ad7b0ed0e54bb74de4a
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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