Hydrochloric Acid → HCID 86681644, compound

HRID 571224Notes

Reaction equation

HRID 571224 reaction equation
C(OC([N:8]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][C:23]([O:25][C@H:26]([C:37]2[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]=2)[CH2:27][C:28]2[C:33]([Cl:34])=[CH:32][N+:31]([O-:35])=[CH:30][C:29]=2[Cl:36])=[O:24])[CH:14]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=O)(C)(C)C.Cl.O1CCOCC1>C(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:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:14]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 89511671HCID 89511671, compound

Product 1

HCID 86681644HCID 86681644, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-4-(2-(2-(3-(N-(tert-butoxycarbonyl)methylsulfonamido)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (297 mg, 0.385 mmol) and 4N HCl in dioxane (2 ml, 8.00 mmol) in DCM (4 ml) was stirred at room temperature for 18 hours. The volatiles were removed under vacuum and the crude was purified by flash chromatography on silica gel (DCM:EtOAc=6:4) to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(methylsulfonamido)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (210 mg, 0.313 mmol, 81% yield). MS/ESI+ 670.36 [MH]+; [αD]=+7.7, c=0.6, MeOH; 1H NMR (300 MHz, DMSO-d6) δ ppm 9.18 (br. s., 1H), 8.51 (s, 2H), 7.67 (d, 1H), 7.29 (s, 1H), 7.04-7.20 (m, 4H), 7.02 (d, 1H), 6.91 (dd, 1H), 7.06 (t, 1H), 6.01 (dd, 1H), 5.23 (d, 1H), 5.06 (d, 1H), 3.85 (d, 2H), 3.42 (dd, 1H), 3.20 (dd, 1H), 2.86 (s, 3H), 1.08-1.31 (m, 1H), 0.54-0.68 (m, 2H), 0.30-0.48 (m, 2H))

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe crude was purified by flash chromatography on silica gel (DCM:EtOAc=6:4)

Sources & evidence

ORD record
ord-aa6e604b342b4c318361e9d9c126cc34
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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