Tris(hydroxymethyl)aminomethane → HCID 42611126, compound

HRID 1897429Notes

Reaction equation

HRID 1897429 reaction equation
[CH2:1]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH2:21][C:22](O)=[O:23])=[CH:11][CH:12]=2)[CH:7]=[N:6]1)[CH:2]([CH3:4])[CH3:3].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[N:67]1([C:73]2[CH:78]=[CH:77][C:76]([NH2:79])=[CH:75][CH:74]=2)[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1.C(O)C(N)(CO)CO>C(Cl)(Cl)Cl>[CH2:1]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH2:21][C:22]([NH:79][C:76]3[CH:75]=[CH:74][C:73]([N:67]4[CH2:68][CH2:69][O:70][CH2:71][CH2:72]4)=[CH:78][CH:77]=3)=[O:23])=[CH:11][CH:12]=2)[CH:7]=[N:6]1)[CH:2]([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 67413337HCID 67413337, compound

Product 1

HCID 42611126HCID 42611126, compoundYield 40.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of (15p) (0.04 g, 0.123 mmol), PyBOP (0.135 g, 0.26 mmol) and DIEA (0.02 mL, 0.12 mmol) in CHCl3 (2 ml), 4-morpholin-4-yl-phenylamine (0.044 g, 0.247 mmol) were added. The mixture was stirred at room temperature for 16 hours, treated with AP-trisamine resin (0.25 g, 2.49 mmol/g), and finally the solvent was removed under reduced pressure after filtration from the resin. The resulting residual was purified by chromatography (Sep-Pak, 10 g) with ether to provide the desired product (16p) (0.024 g, 40%). 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.50 (br s, 1H), 7.45 (dd, J=7.83, 1.57 Hz, 1H), 7.39 (d, J=9.39 Hz, 2H), 7.31-7.26 (m, 3H), 7.23 (dd, J=7.83, 1.57 Hz, 1H), 7.15-7.09 (m, 2H), 6.86-6.79 (m, 3H), 4.17 (d, J=7.04 Hz, 2H), 3.86-3.82 (m, 4H), 3.80 (s, 2H), 3.11-3.06 (m, 4H), 2.41-2.29 (m, 1H), 0.95 (s, CH3), 0.94 (s, CH3); MS (APCI+) m/z 485.2 (M+H) was detected.

Workup

  1. customfinally the solvent was removed under reduced pressure
  2. filtrationafter filtration from the resin
  3. customThe resulting residual was purified by chromatography (Sep-Pak, 10 g) with ether

Sources & evidence

ORD record
ord-c82fea447b9c4e158f6e8bcf97ca5c6d
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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