Triphosgene → HCID 68322434, compound

HRID 1505392Notes

Reaction equation

HRID 1505392 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][C:22]=2[C:29]([F:32])([F:31])[F:30])=[N:18][CH:19]=1.Cl.[CH3:34][C:35]([C:38]([O:40][CH3:41])=[O:39])([CH3:37])[NH2:36]>CCOC(C)=O.C(N(CC)CC)C>[C:25]([C:24]1[CH:27]=[CH:28][C:21]([O:20][C:17]2[N:18]=[CH:19][C:14]([NH:13][C:2]([NH:36][C:35]([CH3:37])([C:38]([O:40][CH3:41])=[O:39])[CH3:34])=[O:4])=[CH:15][CH:16]=2)=[C:22]([C:29]([F:32])([F:30])[F:31])[CH:23]=1)#[N:26]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 13258034Methyl 2-aminoisobutyrate hydrochloride2×HCID 67235649HCID 67235649, compound2×

Product 1

HCID 68322434HCID 68322434, compoundYield 105.5%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of triphosgene (32 mg, 0.11 mmol) in EtOAc (1 ml) at 0° C. was added dropwise a solution of 4-[(5-amino-2-pyridinyl)oxy]-3-(trifluoromethyl)benzonitrile (Intermediate 143, 69.8 mg) in triethylamine (60 μL)/EtOAc (4 mL) and then a suspension of methyl 2-methylalaninate hydrochloride (Intermediate 107, 46 mg) in triethylamine (120 μL)/EtOAc (4 mL). The resulting reaction mixture was stirred for 1 hour. An aqueous pH 3 buffer solution was added to the reaction mixture and the two phases were separated. The aqueous phase was extracted 3 times with EtOAc and the combined organic phases were dried over sodium sulphate and evaporated to dryness to give the title compound (49 mg) as crude. This crude was used in the next step without further purification.

Workup

  1. customThe resulting reaction mixture
  2. customthe two phases were separated
  3. extractionThe aqueous phase was extracted 3 times with EtOAc
  4. dry with materialthe combined organic phases were dried over sodium sulphate
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-2fd9ee808d9445e3b7cfd72b92f8f956
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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