Pyridine → HCID 11686152, compound

HRID 507105Notes

Reaction equation

HRID 507105 reaction equation
[C:1](Cl)(Cl)=[O:2].C1(C)C=CC=CC=1.[CH3:12][O:13][C:14](=[O:20])[C:15]([CH3:19])([CH3:18])[CH2:16][OH:17].C(N(C(C)C)CC)(C)C.[F:30][C:31]([F:65])([F:64])[C:32]1[CH:33]=[C:34]([CH:57]=[C:58]([C:60]([F:63])([F:62])[F:61])[CH:59]=1)[CH2:35][N:36]([C:51]1[N:52]=[N:53][N:54]([CH3:56])[N:55]=1)[C@@H:37]1[C:43]2=[CH:44][C:45]3[CH2:46][CH2:47][CH2:48][C:49]=3[CH:50]=[C:42]2[NH:41][CH2:40][CH2:39][CH2:38]1.N1C=CC=CC=1>ClCCl>[CH3:12][O:13][C:14]([C:15]([CH3:19])([CH3:18])[CH2:16][O:17][C:1]([N:41]1[C:42]2[C:43](=[CH:44][C:45]3[CH2:46][CH2:47][CH2:48][C:49]=3[CH:50]=2)[C@@H:37]([N:36]([CH2:35][C:34]2[CH:33]=[C:32]([C:31]([F:64])([F:65])[F:30])[CH:59]=[C:58]([C:60]([F:61])([F:62])[F:63])[CH:57]=2)[C:51]2[N:52]=[N:53][N:54]([CH3:56])[N:55]=2)[CH2:38][CH2:39][CH2:40]1)=[O:2])=[O:20]

Participants

8

Reactant 6

HCID 1049PyridineHCID 1140TolueneHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 84152Methyl 3-hydroxypivalateHCID 59432477HCID 59432477, compound

Product 1

HCID 11686152HCID 11686152, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Add a 20% solution of phosgene in toluene (0.43 mL, 0.78 mmol) to a mixture of 3-hydroxy-2,2-dimethyl-propionic acid methyl ester (0.12 mL, 0.96 mmol) and diisopropylethylamine (0.16 mL, 0.96 mmol) in dichloromethane (1.8 mL) at 0° C. under nitrogen. Stir the mixture at 0° C. for 10 minutes, then at room temperature for 1 h. To the former solution add a solution of (S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(1,2,3,5,6,7,8,9-octahydro-5-aza-cyclohepta[f]inden-9-yl)-amine (80 mg, 0.16 mmol) in dichloromethane (1.8 mL) followed by pyridine (0.064 mL, 0.78 mmol). Stir the mixture at room temperature for 1 h. Dilute with dichloromethane. Wash with HCl 1M and water. Dry organic layers over anhydrous sodium sulphate and evaporate the solvent. Purify the residue by chromatography (elution with hexane/ethyl acetate) to afford the title compound (78 mg, 73%). MS (ES+): 669 (M+H).

Workup

  1. waitat room temperature for 1 h
  2. stirringStir the mixture at room temperature for 1 h
  3. washWash with HCl 1M and water
  4. customDry organic layers over anhydrous sodium sulphate and evaporate the solvent
  5. customPurify the residue
  6. washby chromatography (elution with hexane/ethyl acetate)

Sources & evidence

ORD record
ord-60df0c5419ce4916916222b70821f890
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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