Ammonia → HCID 10858403, compound

HRID 1594957Notes

Reaction equation

HRID 1594957 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7](Cl)(Cl)=S.[NH3:11].[C:12]([N:20]=C=S)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:23]([NH:31]C(N)=S)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[C:35](=[O:38])([O-])[O-:36].[K+].[K+].[OH2:41].NN.[CH2:44]1[CH2:48][O:47][CH2:46][CH2:45]1>C(Cl)Cl.CO.CO.O.C(O)C.CN(C=O)C.N1C=CC=CC=1>[N:11]1[CH:13]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:14][O:41][C:23]([NH:31][C@H:48]([C:35]([OH:36])=[O:38])[CH2:44][CH:45]([CH3:46])[CH3:7])=[O:30].[N:11]1[CH:24]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:25][O:41][C:48]([CH:44]([CH:45]([CH3:7])[CH3:46])[C@@H:12]([C:35]([OH:36])=[O:38])[NH2:20])=[O:47].[N:11]1[CH:26]=[CH:25][C:24]([CH2:23][O:41][C:12]([NH:20][C@H:48]([C:35]([OH:36])=[O:38])[CH2:44][CH:45]([CH3:46])[CH3:7])=[O:19])=[CH:29][CH:28]=1

Participants

17

Reactant 8

HCID 222AmmoniaHCID 8028TetrahydrofuranHCID 10040ThiophosgeneHCID 11430Potassium CarbonateHCID 24654Hydrazine hydrate (1:1)HCID 68284Benzoyl isothiocyanateHCID 2735473BenzoylthioureaHCID 21226445Aluminium lithium hydride

Product 3

HCID 10858403HCID 10858403, compoundHCID 10880017N-(2-pyridinylmethoxycarbonyl)-L-leucineHCID 70237521HCID 70237521, compound

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 887MethanolSolventHCID 1049PyridineSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 22242641Methanol--water (1/1)Solvent

Procedure

Compounds wherein X═S, Y═CH, Z═N and V═NR66R67, are prepared by methods analogous to those described in Scheme 21. An acid chloride (1-Scheme 21) is treated with a primary amine (such as 4-aminobiphenyl or aniline) and pyridine in an aprotic solvent (such as methylene chloride) to provide 2-Scheme 21, which is treated with lithium aluminum hydride in THF to afford 3-Scheme 25. Treatment of 3-Scheme 21 with thiophosgene and pyridine in methylene chloride, followed by treanment with ammonia in methanol provides 4-Scheme 21. Alternatively, 4-Scheme 21 may be prepared by treatment of 3-Scheme 21 with benzoyl isothiocyanate, followed by treatment of the intermediate benzoyl thiourea with potassium carbonate in methanol/water. 4-Scheme 21 is treated with hydrazine hydrate in ethanol to give 5-Scheme 21. Treatment of 5-Scheme 21 with a carboxylic acid (such as N-(2-pyridinylmethoxycarbonyl)-L-leucine, N-(3-pyridinylmethoxycarbonyl-L-leucine or N-(4-pyridinylmethoxycarbonyl)-L-leucine) and a peptide coupling reagent (such as EDC.HCl/1-HOBT) in an aprotic solvent (such as DMF) affords 6-Scheme 21.

Workup

  1. customZ═N and V═NR66R67, are prepared by methods analogous to
  2. customto provide 2-Scheme 21, which
  3. customto afford 3-Scheme 25
  4. customprovides 4-Scheme 21
  5. customto give 5-Scheme 21

Sources & evidence

ORD record
ord-ac540ba26c414dc28caddd940bc35537
Source dataset
uspto-grants-2001_09
Patent number
US06284777B1

Reaction notes

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