Trimethylsilyl isocyanate → 1-(1-(1-(4-chloro-3-((R)-1-(2,4-dichlorophenyl)ethylamino)phenyl)piperidin-4-yl)pyrrolidin-3-yl)urea

HRID 75140Notes

Reaction equation

HRID 75140 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[NH:20][C@@H:21]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[Cl:30])[CH3:22].C[Si]([N:35]=[C:36]=[O:37])(C)C>C1COCC1.C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][CH:16]([NH:19][C:36]([NH2:35])=[O:37])[CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[NH:20][C@@H:21]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[Cl:30])[CH3:22]

Participants

5

Reactant 2

HCID 70696Trimethylsilyl isocyanateHCID 86689059HCID 86689059, compound

Product 1

HCID 715818821-(1-(1-(4-chloro-3-((R)-1-(2,4-dichlorophenyl)ethylamino)phenyl)piperidin-4-yl)pyrrolidin-3-yl)ureaYield 26%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 1-(1-(4-chloro-3-((R)-1-(2,4-dichlorophenyl)ethylamino)phenyl)piperidin-4-yl)pyrrolidin-3-amine (0.056 g, 0.12 mmol) in THF (1 mL) and acetic acid (1 drop) was added a solution of (trimethylsily)isocyanate (0.015 g, 0.13 mmol) in THF (0.5 mL). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was quenched with diluted with aqueous saturated sodium bicarbonate and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane) to afford the desired product as a white solid (0.016 g, 0.031 mmol, 26%). 1H NMR (400 MHz, CDCl3) δ 7.36-7.32 (m, 2H), 7.16 (dd, J=2.2, 8.4 Hz, 1H), 7.04 (d, J=8.6 Hz, 1H), 6.82 (br, 1H), 6.16 (dd, J=2.5, 8.8 Hz, 1H), 5.77 (br, 1H), 5.23 (br, 1H), 4.87 (q, J=6.6 Hz, 1H), 4.64 (d, J=5.2 Hz, 1H), 3.44-3.37 (m, 2H), 3.08-2.82 (m, 3H), 2.69-2.40 (m, 4H), 2.25-1.85 (m, 6H), 1.60-1.42 (m, 5H); MS: (ES) m/z calculated for C24H31Cl3N5O [M+H]+ 510.2. found 510.

Workup

  1. customThe reaction mixture was quenched
  2. additionwith diluted with aqueous saturated sodium bicarbonate
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-dbe795f1da8e4ec4a62390b96e5cbdbc
Source dataset
uspto-grants-2014_09
Patent number
US08835419B2

Reaction notes

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