1,1-Dichloroethane → HCID 57870281, compound

HRID 1698329Notes

Reaction equation

HRID 1698329 reaction equation
C1C2C(COC([N:18]3[CH2:23][C@H:22]([C:24](=[O:44])[N:25]([CH:41]4[CH2:43][CH2:42]4)[CH2:26][C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[N:29]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:28]=4)[CH2:21][C@H:20]([NH2:45])[CH2:19]3)=O)C3C(=CC=CC=3)C=2C=CC=1.ClC(Cl)C.[C:50]([N:54]=[C:55]=[O:56])([CH3:53])([CH3:52])[CH3:51]>C(Cl)Cl>[CH:41]1([N:25]([CH2:26][C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:28]=2)[C:24]([C@@H:22]2[CH2:21][C@H:20]([NH:45][C:55]([NH:54][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:56])[CH2:19][NH:18][CH2:23]2)=[O:44])[CH2:42][CH2:43]1

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 62412tert-Butyl isocyanateHCID 67274027(3S,5R)-3-amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 57870281HCID 57870281, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (3S,5R)-3-amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (115 A.) (374 mg, 0.62 mmol), dichloroethane (5 mL) and tert-butyl isocyanate (142 μl, 1.24 mmol) is shaken for 14 h at 50° C. The mixture is diluted with CH2Cl2 and washed with 1 N HCl and saturated NaHCO3 solution. The organic layer is dried (Na2SO4) and evaporated. The crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (6 ml) for 1 h, the mixture is evaporated and the residue purified by preparative HPLC (YMC Pack Pro C18, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 mL/min). The combined pure fractions are treated with K2CO3, 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 yellow resin. MS: 484.2 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.05 min.

Workup

  1. washwashed with 1 N HCl and saturated NaHCO3 solution
  2. dry with materialThe organic layer is dried (Na2SO4)
  3. customevaporated
  4. customthe mixture is evaporated
  5. customthe residue purified by preparative HPLC (YMC Pack Pro C18, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 mL/min)
  6. additionThe combined pure fractions are treated with K2CO3, CH3CN
  7. customis removed in vacuo
  8. extractionthe residual aqueous phase is extracted three times with CH2Cl2
  9. dry with materialThe combined organic layers are dried (Na2SO4)
  10. customevaporated

Sources & evidence

ORD record
ord-81783eae67424edcab3329a5a0e87033
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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