Stannous chloride dihydrate → [(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 2-[5-(hydroxyamino)-1,3-dioxoisoindol-2-yl]acetate

HRID 571285Notes

Reaction equation

HRID 571285 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:44])[CH:5]=[C:6]([Cl:43])[C:7]=1[CH2:8][C@@H:9]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH:40]2[CH2:42][CH2:41]2)[CH:29]=1)[O:10][C:11](=[O:27])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N+:23]([O-])=[O:24])[CH:19]=2)[C:14]1=[O:26].O.O.[Sn](Cl)Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:44])[CH:5]=[C:6]([Cl:43])[C:7]=1[CH2:8][C@@H:9]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:36])[F:37])=[C:30]([O:38][CH2:39][CH:40]2[CH2:41][CH2:42]2)[CH:29]=1)[O:10][C:11](=[O:27])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([NH:23][OH:24])[CH:19]=2)[C:14]1=[O:26]

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 86681606HCID 86681606, compound

Product 1

HCID 178521246[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 2-[5-(hydroxyamino)-1,3-dioxoisoindol-2-yl]acetateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-nitro-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (60 mg, 0.092 mmol) was dissolved in THF (5 ml), and added with tin(II) chloride dihydrate (25.0 mg, 0.111 mmol). The reaction was stirred at RT for 18 hours. THF was evaporated under vacuum at RT, and the residue quenched by addition of K2CO3/H2O (15% w/w; 50 ml) and extracted with EtOAc (50 ml). The organic phase was extracted with K2CO3/H2O (15% w/w) (×3), dried over Na2SO4 and the solvent removed under reduced pressure to yield the title compound (35.0 mg, 0.055 mmol, 60% yield). 1H NMR (400 MHz, acetone) ppm 8.80 (bs, 1H), 8.32 (bs, 1H), 8.18 (s, 2H), 7.70 (d, J=8.38 Hz, 1H), 7.36 (d, J=1.76 Hz, 1H), 7.28 (dd, J=8.16, 1.98 Hz, 1H), 7.15-7.23 (m, 2H), 7.03 (dd, J=8.38, 1.76 Hz, 1H), 6.93 (t, 1H, CHF2), 6.13 (dd, J=9.48, 4.63 Hz, 1H), 4.39 (s, 2H), 4.00 (dd, J=7.06, 3.09 Hz, 2H), 3.51 (dd, J=14.33, 9.48 Hz, 1H), 3.31 (dd, J=14.11, 4.41 Hz, 1H), 1.24-1.36 (m, 1H), 0.53-0.71 (m, 2H), 0.31-0.49 (m, 2H). MS/ESI+ [MH]+=637.9

Workup

  1. customTHF was evaporated under vacuum at RT
  2. customthe residue quenched by addition of K2CO3/H2O (15% w/w; 50 ml)
  3. extractionextracted with EtOAc (50 ml)
  4. extractionThe organic phase was extracted with K2CO3/H2O (15% w/w) (×3)
  5. dry with materialdried over Na2SO4
  6. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-ed717193c262412b95d5992a814f08a7
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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