2-[2-(2-Methoxyethoxy)ethoxy]acetyl chloride → N-{(7R)-6-Cyano-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-2-[2-(2-methoxyethoxy)ethoxy]acetamide

HRID 1046860Notes

Reaction equation

HRID 1046860 reaction equation
Cl.[NH2:2][C:3]1[N:32]=[C:6]2[N:7]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[C:8]([CH3:21])=[C:9]([C:19]#[N:20])[C@@H:10]([C:11]3[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=3)[N:5]2[N:4]=1.[CH3:33][O:34][CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][C:42](Cl)=[O:43]>N1C=CC=CC=1>[C:19]([C:9]1[C@@H:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)[N:5]2[N:4]=[C:3]([NH:2][C:42](=[O:43])[CH2:41][O:40][CH2:39][CH2:38][O:37][CH2:36][CH2:35][O:34][CH3:33])[N:32]=[C:6]2[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:29])([F:31])[F:30])[CH:23]=2)[C:8]=1[CH3:21])#[N:20]

Participants

4

Reactant 2

HCID 27595712-[2-(2-Methoxyethoxy)ethoxy]acetyl chlorideHCID 66627899(7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride

Product 1

HCID 46841343N-{(7R)-6-Cyano-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-2-[2-(2-methoxyethoxy)ethoxy]acetamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Under an atmosphere of argon protective gas, (7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride (14 mg, 31 μmol) was dissolved in abs. pyridine (0.7 ml). At room temperature, 2-[2-(2-methoxy-ethoxy)ethoxy]acetyl chloride (12 mg, 61 μmol, 2 eq.) was added. After 12 h, analysis of the reaction by HPLC showed substantial conversion. The reaction mixture was concentrated under reduced pressure and purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (12.4 mg, 70% of theory).

Workup

  1. customanalysis of the reaction by HPLC
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompurified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
  4. customAfter lyophilization, the product was obtained as a solid (12.4 mg, 70% of theory)

Sources & evidence

ORD record
ord-8206c3a1dae64bb391dfaea228ad3cf6
Source dataset
uspto-grants-2013_10
Patent number
US08569314B2

Reaction notes

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