Diisopropylethylamine → HCID 15984410, compound

HRID 1698301Notes

Reaction equation

HRID 1698301 reaction equation
C1C2C(COC([N:18]3[CH2:23][C@H:22]([NH:24][S:25]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH2:21][C@H:20]([C:35]([OH:37])=O)[CH2:19]3)=O)C3C(=CC=CC=3)C=2C=CC=1.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[CH3:72][O:73][CH2:74][CH2:75][CH2:76][CH2:77][O:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][C:80]=1[CH:85]([C:88]1[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=1)[CH2:86][NH2:87]>C(Cl)Cl.CC#N>[CH3:72][O:73][CH2:74][CH2:75][CH2:76][CH2:77][O:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][C:80]=1[CH:85]([C:88]1[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=1)[CH2:86][NH:87][C:35]([C@H:20]1[CH2:21][C@@H:22]([NH:24][S:25]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)(=[O:26])=[O:27])[CH2:23][NH:18][CH2:19]1)=[O:37]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 57870358HCID 57870358, compoundHCID 67273395HCID 67273395, compound

Product 1

HCID 15984410HCID 15984410, compound

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

An ice-cooled mixture of (3S*,5R*)-5-(toluene-4-sulfonylamino)-piperidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (208.2 mg, 0.4 mmol), O-(1H-6-chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (182 mg, 0.44 mmol) and N-ethyldiisopropylamine (27.4 μL, 0.16 mmol) in CH2Cl2/CH3CN 1:1 (3 mL) is stirred for 10 min. After the addition of 2-[2-(4-methoxy-butoxy)-phenyl]-2-phenyl-ethylamine (119.8 mg, 0.4 mmol), the ice-bath is removed and stirring is continued for 14 h at RT. The reaction mixture is distributed between ethyl acetate and 10% K2CO3 solution. The aqueous layer is separated and extracted twice with ethyl acetate. The combined organic layers are dried over Na2SO4 and evaporated in vacuo. The residue is stirred for 1 h with a freshly prepared mixture of CH2Cl2/piperidine 4:1 (5 mL), evaporated and the residue purified by preparative HPLC (C18 column; 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA/20 min, flow 20 mL/min). The combined pure fractions are treated with Na2CO3, CH3CN is removed in vacuo, and the residual aqueous phase is extracted three times with CH2Cl2. The combined organic layers are dried (Na2SO4) and evaporated to afford the title compound as a slightly beige amorphous solid. MS: 580.4 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.61 min.

Workup

  1. customthe ice-bath is removed
  2. stirringstirring
  3. waitis continued for 14 h at RT
  4. customThe aqueous layer is separated
  5. extractionextracted twice with ethyl acetate
  6. dry with materialThe combined organic layers are dried over Na2SO4
  7. customevaporated in vacuo
  8. stirringThe residue is stirred for 1 h with a freshly prepared mixture of CH2Cl2/piperidine 4:1 (5 mL)
  9. customevaporated
  10. customthe residue purified by preparative HPLC (C18 column; 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA/20 min, flow 20 mL/min)
  11. additionThe combined pure fractions are treated with Na2CO3, CH3CN
  12. customis removed in vacuo
  13. extractionthe residual aqueous phase is extracted three times with CH2Cl2
  14. dry with materialThe combined organic layers are dried (Na2SO4)
  15. customevaporated

Sources & evidence

ORD record
ord-e31314fc857e4c61b765e2f94b28d7c2
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

Loading…