HCID 86681727, compound → HCID 86681726, compound

HRID 571317Notes

Reaction equation

HRID 571317 reaction equation
C(OC([N:8]([CH2:57][CH2:58][O:59][CH3:60])[CH2:9][CH2:10][N:11]([C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[C:21](=[O:25])[N:20]([CH2:26][C:27]([O:29][C@H:30]([C:41]1[CH:46]=[CH:45][C:44]([O:47][CH:48]([F:50])[F:49])=[C:43]([O:51][CH2:52][CH:53]3[CH2:55][CH2:54]3)[CH:42]=1)[CH2:31][C:32]1[C:37]([Cl:38])=[CH:36][N+:35]([O-:39])=[CH:34][C:33]=1[Cl:40])=[O:28])[C:19]2=[O:56])[S:12]([CH3:15])(=[O:14])=[O:13])=O)(C)(C)C>C(Cl)Cl.Cl.O1CCOCC1>[Cl:40][C:33]1[CH:34]=[N+:35]([O-:39])[CH:36]=[C:37]([Cl:38])[C:32]=1[CH2:31][C@@H:30]([C:41]1[CH:46]=[CH:45][C:44]([O:47][CH:48]([F:49])[F:50])=[C:43]([O:51][CH2:52][CH:53]2[CH2:54][CH2:55]2)[CH:42]=1)[O:29][C:27](=[O:28])[CH2:26][N:20]1[C:19](=[O:56])[C:18]2[C:22](=[CH:23][CH:24]=[C:16]([N:11]([CH2:10][CH2:9][NH:8][CH2:57][CH2:58][O:59][CH3:60])[S:12]([CH3:15])(=[O:13])=[O:14])[CH:17]=2)[C:21]1=[O:25]

Participants

5

Reactant 1

HCID 86681727HCID 86681727, compound

Product 1

HCID 86681726HCID 86681726, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (S)-4-(2-(2-(5-(N-(2-(tert-butoxycarbonyl(2-methoxyethyl)amino)ethyl)methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.078 g, 0.086 mmol) in dry DCM (3 ml), 4M HCl in dioxane (0.103 ml, 0.412 mmol) was added, and the mixture was stirred for at room temperature overnight. Additional 4M HCl in dioxane (0.086 ml, 0.344 ml) was added, and the reaction was stirred at the same temperature for 72 hours. The mixture was washed with aqueous sat. NaHCO3; the organic phase was dried over sodium sulfate and the solvent was removed affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N-(2-(2-methoxyethylamino)ethyl)methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide as a yellow solid (54.72 mg, 0.068 mmol, 79% yield, MS/ESI+ 801.13 [MH]+, [αD]=−20.82, c=0.512, MeOH). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.43 (s, 2H), 7.98 (s, 1H), 7.96 (dd, 1H), 7.90 (dd, 1H), 7.19 (d, 1H), 7.09 (d, 1H), 6.97 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.43 (s, 2H), 3.91-4.02 (m, 2H), 3.86 (t, 2H), 3.39 (dd, 1H), 3.30 (t, 2H), 3.23 (dd, 1H), 3.19 (s, 3H), 3.13 (s, 3H), 2.56-2.67 (m, 4H), 1.05-1.38 (m, 1H), 0.48-0.69 (m, 2H), 0.27-0.48 (m, 2H).

Workup

  1. stirringthe reaction was stirred at the same temperature for 72 hours
  2. washThe mixture was washed with aqueous sat. NaHCO3
  3. dry with materialthe organic phase was dried over sodium sulfate
  4. customthe solvent was removed

Sources & evidence

ORD record
ord-f1e3d91ca59c405d9a3b453cf206012c
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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