1,2-Dichloroethane → HCID 71547044, compound

HRID 571233Notes

Reaction equation

HRID 571233 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH2:10][N:9]([CH2:16][C:17]([OH:19])=[O:18])[CH2:8][CH2:7]2.C(Cl)CCl.[Cl:24][C:25]1[CH:26]=[N+:27]([O-:50])[CH:28]=[C:29]([Cl:49])[C:30]=1[CH2:31][C@@H:32]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]2[CH2:48][CH2:47]2)[CH:35]=1)O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:24][C:25]1[CH:26]=[N+:27]([O-:50])[CH:28]=[C:29]([Cl:49])[C:30]=1[CH2:31][C@@H:32]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]2[CH2:48][CH2:47]2)[CH:35]=1)[O:18][C:17](=[O:19])[CH2:16][N:9]1[CH2:8][CH2:7][C:6]2[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([O:3][CH3:2])[CH:5]=2)[CH2:10]1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 45599134HCID 45599134, compoundHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 71547044HCID 71547044, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetic acid hydrochloride (822 mg, 2.86 mmol) in anhydrous DCM (30 ml), DMAP (523 mg, 4.28 mmol) and EDC (712 mg, 3.71 mmol) were added. The mixture was stirred at room temperature for 1 hour and then (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (1.200 g, 2.86 mmol) was added. The mixture was stirred at room temperature for 48 hours, then diluted with DCM and washed with 1N HCl, dried over Na2SO4 and evaporated. The desired product was first purified by flash chromatography on silica gel (DCM:MeOH 10:0.2) followed by preparative HPLC (Method 2). The title compound was obtained (1.354 g, 73% yield). MS/ESI+ 653.18 [MH]+; [αD]=−43.91, c=0.69 in MeOH); 1H NMR (300 MHz, DMSO-d6) δ ppm 8.60 (s, 2H) 7.20 (d, 1H) 7.13 (d, 1H) 7.01 (dd, 1H) 7.07 (t, 1H) 6.64 (s, 1H) 6.58 (s, 1H) 6.10 (dd, 1H) 3.81-3.99 (m, 2H) 3.70 (s, 3H) 3.71 (s, 3H) 3.35-3.56 (m, 4H) 3.19-3.28 (m, 2H) 2.57-2.81 (m, 4H) 1.11-1.34 (m, 1H) 0.49-0.67 (m, 2H) 0.16-0.44 (m, 2H).

Workup

  1. additionwere added
  2. stirringThe mixture was stirred at room temperature for 48 hours
  3. washwashed with 1N HCl
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe desired product was first purified by flash chromatography on silica gel (DCM:MeOH 10:0.2)

Sources & evidence

ORD record
ord-8d2eca35b3d948b7848684746a2d4cad
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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