1,4-Dioxane → HCID 71553992, compound

HRID 571212Notes

Reaction equation

HRID 571212 reaction equation
C(OC([N:8]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([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]3[CH2:51][CH2:50]3)[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])[CH:17]=[CH:16]2)[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:18]1[C:19]2[C:15](=[CH:14][C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:21][CH:20]=2)[CH:16]=[CH:17]1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 89511939HCID 89511939, compound

Product 1

HCID 71553992HCID 71553992, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-4-(2-(2-(5-(N-(tert-butoxycarbonyl)methylsulfonamido)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (170 mg, 0.221 mmol) in DCM (10 ml), 4M HCl in dioxane (552 μl, 2.206 mmol) was added, and the mixture was reacted overnight at room temperature. The solvent was evaporated and the resulting crude was purified by preparative HPLC (Method 1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(methylsulfonamido)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (63 mg, 0.094 mmol, 43% yield). MS/ESI+ 670.09 [MH]+, [αD]=7.68, c=0.5 in DCM. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.27 (s, 1H) 8.51 (s, 2H) 7.42 (d, 1H) 7.29 (d, 1H) 7.13-7.22 (m, 2H) 7.02 (d, 1H) 7.02 (dd, 1H) 6.91 (dd, 1H) 7.05 (t, 1H) 6.44 (dd, 1H) 6.01 (dd, 1H) 5.21 (d, 1H) 5.06 (d, 1H) 3.87 (d, 2H) 3.41 (dd, 1H) 3.21 (dd, 1H) 2.87 (s, 3H) 1.13-1.32 (m, 1H) 0.50-0.71 (m, 2H) 0.22-0.48 (m, 2H)

Workup

  1. customthe mixture was reacted overnight at room temperature
  2. customThe solvent was evaporated
  3. customthe resulting crude was purified by preparative HPLC (Method 1)

Sources & evidence

ORD record
ord-85c9afe015ba4cfbba1886f16a30efee
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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