Chlorotrimethylsilane → HCID 13002085, compound

HRID 1106192Notes

Reaction equation

HRID 1106192 reaction equation
[C:1]([NH:11][C@@H:12]([C:18]([OH:20])=O)[CH2:13][CH2:14][C:15](=[O:17])[NH2:16])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN1CCOCC1.ClC(OC)=O.[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[NH:41][C:42](=[O:49])[C:43](=[CH:47][CH:48]=2)[C:44]([OH:46])=[O:45])=[CH:36][CH:35]=1.Cl[Si](C)(C)C.C(N(CC)CC)C>ClCCl.C(O)(C)C.CN(C)C(=O)C>[C:1]([NH:11][C@@H:12]([C:18]([NH:33][C:34]1[CH:35]=[CH:36][C:37]([C:40]2[NH:41][C:42](=[O:49])[C:43](=[CH:47][CH:48]=2)[C:44]([OH:46])=[O:45])=[CH:38][CH:39]=1)=[O:20])[CH2:13][CH2:14][C:15](=[O:17])[NH2:16])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

10

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 6586Methyl chloroformateHCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 1810769N-Cbz-D-GlutamineHCID 129189566-(4-Aminophenyl)-1,2-dihydro-2-oxonicotinic acid

Product 1

HCID 13002085HCID 13002085, compoundYield 89.3%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 4.2 g (15 mmol) of N-carbobenzoxy-D-glutamine and 50 ml of N,N-dimethylacetamide is stirred at -12° and 1.65 ml (15 mmol) of N-methylmorpholine and 1.2 ml (15 mmol) of methyl chloroformate are added. The mixture is stirred at -12° for 15 min. A suspension of 2.3 g (10 mmol) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid is stirred in 75 ml dichloromethane at room temperature and is silylated with 3.8 ml (30 mmol) of chlorotrimethylsilane and 4.2 ml (30 mmol) of triethylamine. The solution of the silylated material is cooled to 0°-5° and is then added to the solution of the above mixed anhydride. The reaction mixture is stirred at -7° for 1 hr, then at 0°-5° for 4 hrs and at room temperature for 16 hrs and 30 ml of isopropanol is added. The bulk of the solvents is removed at reduced pressure and the residue is diluted with 250 ml cold water. The precipitate is collected, washed with cold water and dried to give 4.4 g of 6-[4-(N-carbobenzoxy-D-glutaminylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid as a yellow solid; mp 250°-252° dec; [α]D23 -13.3° (cl, DMSO).

Workup

  1. temperatureThe solution of the silylated material is cooled to 0°-5°
  2. additionis then added to the solution of the
  3. stirringThe reaction mixture is stirred at -7° for 1 hr
  4. waitat 0°-5° for 4 hrs
  5. waitat room temperature for 16 hrs
  6. customThe bulk of the solvents is removed at reduced pressure
  7. additionthe residue is diluted with 250 ml cold water
  8. customThe precipitate is collected
  9. washwashed with cold water
  10. customdried

Sources & evidence

ORD record
ord-21021071a11641658701fb51832c3025
Source dataset
uspto-grants-1982_01
Patent number
US04311698

Reaction notes

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