1,2-Dichloroethane → HCID 86681737, compound

HRID 571324Notes

Reaction equation

HRID 571324 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].Cl.[O:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][N:37]([C:42]2[CH:55]=[CH:54][C:45]3[N:46]([CH2:50][C:51](O)=[O:52])[C:47](=[O:49])[O:48][C:44]=3[CH:43]=2)[S:38]([CH3:41])(=[O:40])=[O:39])[CH2:31][CH2:30]1.C(Cl)CCl.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[O:10][C:51](=[O:52])[CH2:50][N:46]1[C:45]2[CH:54]=[CH:55][C:42]([N:37]([CH2:36][CH2:35][N:32]3[CH2:33][CH2:34][O:29][CH2:30][CH2:31]3)[S:38]([CH3:41])(=[O:40])=[O:39])=[CH:43][C:44]=2[O:48][C:47]1=[O:49]

Participants

7

Reactant 4

HCID 111,2-Dichloroethane2×HCID 313Hydrochloric AcidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 86681738HCID 86681738, compound

Product 1

HCID 86681737HCID 86681737, compoundYield 37.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (281 mg, 0.669 mmol), 2-(6-(N-(2-morpholinoethyl)-methylsulfonamido)-2-oxobenzo[d]oxazol-3(2H)-yl)acetic acid hydrochloride (350 mg, 0.803 mmol), EDC (192 mg, 1.004 mmol) and DMAP (204 mg, 1.673 mmol) were dissolved in dry DCM (8 ml), and the mixture was reacted at room temperature for 5 hours. Additional EDC (128 mg, 0.669 mmol) and DMAP (82 mg, 0.669 mmol) were added, and the reaction was stirred at the same temperature overnight. Thus, the mixture was treated with 1N HCl (30 ml) and extracted with DCM (2×100 ml). The organic phase was washed with brine and dried over Na2SO4; the solvent was removed under reduced pressure and the resulting crude was purified by flash chromatography (DCM/MeOH 98/2 to 90/10) yielding (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(6-(N-(2-morpholinoethyl)methylsulfonamido)-2-oxobenzo[d]oxazol-3(2H)-yl)acetoxy)ethyl)pyridine 1-oxide (203 mg, 0.253 mmol, 37.8% yield, MS/ESI+ 801.15 [MH]+, [αD]=−20.63, c=0.505, DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.39 (s, 2H), 7.52 (d, 1H), 7.27 (dd, 1H), 7.22 (d, 1H), 7.20 (d, 1H), 7.11 (d, 1H), 6.97 (dd, 1H), 7.08 (t, 1H), 6.04 (dd, 1H), 4.86 (d, 1H), 4.72 (d, 1H), 3.94 (d, 2H), 3.74 (t, 2H), 3.46-3.57 (m, 4H), 3.38 (dd, 1H), 3.22 (dd, 1H), 3.09 (s, 3H), 2.22-2.44 (m, 6H), 1.16-1.31 (m, 1H), 0.50-0.66 (m, 2H), 0.28-0.46 (m, 2H).

Workup

  1. customthe mixture was reacted at room temperature for 5 hours
  2. extractionextracted with DCM (2×100 ml)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was removed under reduced pressure
  6. customthe resulting crude was purified by flash chromatography (DCM/MeOH 98/2 to 90/10)

Sources & evidence

ORD record
ord-e731898228224ec8b8eb28e13026faec
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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