Stannous chloride dihydrate → (S)-4-(2-(2-(4-amino-1,3-dioxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4 (difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

HRID 571287Notes

Reaction equation

HRID 571287 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)[CH:19]=2)[C:14]1=[O:26].O.O.[Sn](Cl)Cl>C1COCC1>[NH2:23][C:18]1[CH:17]=[CH:16][CH:15]=[C:20]2[C:19]=1[C:14](=[O:26])[N:13]([CH2:12][C:11]([O:10][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]3[CH2:41][CH2:42]3)[CH:29]=1)[CH2:8][C:7]1[C:6]([Cl:43])=[CH:5][N+:4]([O-:44])=[CH:3][C:2]=1[Cl:1])=[O:27])[C:21]2=[O:22]

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 86681606HCID 86681606, compound

Product 1

HCID 86681605(S)-4-(2-(2-(4-amino-1,3-dioxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4 (difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxideYield 66%

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 (80 mg, 0.123 mmol) was dissolved in THF (10 ml), and added with tin(II) chloride dihydrate (80.0 mg, 0.355 mmol). The reaction was stirred at RT for 3 days. The reaction was quenched by addition of K2CO3/H2O (15% w/w; 50 ml). The solid precipitated was filtered on paper, and the solution extracted with EtOAc (50 ml). The organic phase was washed with K2CO3/H2O conc. (×3), dried over Na2SO4 and the solvent removed to yield the titled compound (50.0 mg) as yellow oil (yield=66%). 1H NMR (400 MHz, acetone) ppm 8.20 (s, 2H), 7.50 (d, J=7.50 Hz, 1H), 7.14-7.24 (m, 2H), 7.01-7.13 (m, 3H), 6.92 (t, J=75.00 Hz, 1H), 6.17 (dd, J=9.48, 5.07 Hz, 3H), 4.37 (d, J=7.50 Hz, 2H), 4.00 (dd, J=7.06, 3.09 Hz, 2H), 3.53 (m, 1H), 3.34 (d, J=4.41 Hz, 1H), 1.30 (br. s., 2H), 0.56-0.68 (m, 2H), 0.41 (d, J=4.41 Hz, 2H). MS/ESI+ [MH]+=608.39.

Workup

  1. customThe reaction was quenched by addition of K2CO3/H2O (15% w/w; 50 ml)
  2. customThe solid precipitated
  3. filtrationwas filtered on paper
  4. extractionthe solution extracted with EtOAc (50 ml)
  5. washThe organic phase was washed with K2CO3/H2O conc. (×3)
  6. dry with materialdried over Na2SO4
  7. customthe solvent removed

Sources & evidence

ORD record
ord-698a77753dbe4486ae78e9327f6311a7
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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