1,4-Dioxane → HCID 86681631, compound

HRID 571218Notes

Reaction equation

HRID 571218 reaction equation
C(OC([N:8]([C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][N:17]2[CH2:22][C:23]([O:25][C@H:26]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH:44]([F:46])[F:45])=[C:39]([O:47][CH2:48][CH:49]2[CH2:51][CH2:50]2)[CH:38]=1)[CH2:27][C:28]1[C:33]([Cl:34])=[CH:32][N+:31]([O-:35])=[CH:30][C:29]=1[Cl:36])=[O:24])[S:9]([CH3:12])(=[O:11])=[O:10])=O)(C)(C)C.O1CCOCC1>C(Cl)Cl.Cl>[Cl:36][C:29]1[CH:30]=[N+:31]([O-:35])[CH:32]=[C:33]([Cl:34])[C:28]=1[CH2:27][C@@H:26]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH:44]([F:45])[F:46])=[C:39]([O:47][CH2:48][CH:49]2[CH2:51][CH2:50]2)[CH:38]=1)[O:25][C:23](=[O:24])[CH2:22][N:17]1[C:18]2[C:14](=[C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:21]=[CH:20][CH:19]=2)[CH:15]=[CH:16]1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 89512127HCID 89512127, compound

Product 1

HCID 86681631HCID 86681631, compoundYield 49.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (420 mg, 0.545 mmol) in DCM (10 ml), 4M HCl in dioxane (1.363 ml, 5.45 mmol) was added, and the mixture was stirred at room temperature overnight. The solvent was evaporated and the resulting crude was purified by HPLC preparative (Method 3) recovering (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-(methylsulfonamido)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (180 mg, 0.268 mmol, 49% yield). MS/ESI+ 670.09 [MH]+; [αD]=−14.56, c=0.5 in DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 9.51 (s, 1H) 8.52 (s, 2H) 7.24 (d, 1H) 7.16 (d, 1H) 6.96-7.12 (m, 4H) 6.92 (dd, 1H) 7.06 (t, 1H) 6.76 (d, 1H) 6.02 (dd, 1H) 5.22 (d, 1H) 5.05 (d, 1H) 3.89 (d, 2H) 3.41 (dd, 1H) 3.21 (dd, 1H) 2.95 (s, 3H) 1.10-1.33 (m, 1H) 0.51-0.69 (m, 2H) 0.27-0.44 (m, 2H).

Workup

  1. customThe solvent was evaporated
  2. customthe resulting crude was purified by HPLC preparative (Method 3)

Sources & evidence

ORD record
ord-cf783f45a3a748d49f7360055d6946f3
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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