4-Isocyanato-1,2-dimethoxybenzene → HCID 86679581, compound

HRID 1776623Notes

Reaction equation

HRID 1776623 reaction equation
Cl.[NH2:2][CH2:3][C:4]([O:6][C@H:7]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([O:28][CH2:29][CH:30]2[CH2:32][CH2:31]2)[CH:19]=1)[CH2:8][C:9]1[C:14]([Cl:15])=[CH:13][N+:12]([O-:16])=[CH:11][C:10]=1[Cl:17])=[O:5].C(OC(NCC(O[C@H](C1C=CC(OC(F)F)=C(OCC2CC2)C=1)CC1C(Cl)=C[N+]([O-])=CC=1Cl)=O)=O)(C)(C)C.[N:71]([C:74]1[CH:79]=[CH:78][C:77]([O:80][CH3:81])=[C:76]([O:82][CH3:83])[CH:75]=1)=[C:72]=[O:73]>CN(C=O)C.O>[Cl:17][C:10]1[CH:11]=[N+:12]([O-:16])[CH:13]=[C:14]([Cl:15])[C:9]=1[CH2:8][C@@H:7]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([O:28][CH2:29][CH:30]2[CH2:32][CH2:31]2)[CH:19]=1)[O:6][C:4](=[O:5])[CH2:3][NH:2][C:72]([NH:71][C:74]1[CH:79]=[CH:78][C:77]([O:80][CH3:81])=[C:76]([O:82][CH3:83])[CH:75]=1)=[O:73]

Participants

6

Reactant 3

HCID 35178104-Isocyanato-1,2-dimethoxybenzeneHCID 86679412HCID 86679412, compoundHCID 86679413HCID 86679413, compound

Product 1

HCID 86679581HCID 86679581, compoundYield 36.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(S)-4-(2-(2-aminoacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide hydrochloride (prepared in an analogous manner as described in Scheme 1, Step 1 and 2, Compound 3) (21 mg, 0.042 mmol) was dissolved in DMF dry (1 ml). 4-isocyanato-1,2-dimethoxybenzene (15.02 mg, 0.084 mmol) was added, and the reaction was stirred at RT overnight. The reaction mixture was diluted with water and extracted with EtOAc. The organic phase was washed with HCl 1N, dried over Na2SO4 and concentrated under vacuum. The crude product was purified by Preparative reverse-phase HPLC to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(3,4-dimethoxyphenyl)ureido)acetoxy)ethyl)pyridine 1-oxide (10 mg, 36.4% yield).

Workup

  1. customdry (1 ml)
  2. extractionextracted with EtOAc
  3. washThe organic phase was washed with HCl 1N
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by Preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-d8e8873be4a74796ae03346edd96f6cb
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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