1,2-Dichloroethane → HCID 178445681, compound

HRID 1992804Notes

Reaction equation

HRID 1992804 reaction equation
[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]([C:14]2[N:18]([CH2:19][C:20]3[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][N:21]=3)[N:17]=[C:16]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=3)[CH:15]=2)=[O:13])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.[NH2:47][C:48]1[NH:52][N:51]=[N:50][N:49]=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.C(OCC)(=O)C>[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]([C:14]2[N:18]([CH2:19][C:20]3[CH:28]=[CH:27][C:23]([C:24]([NH:47][C:48]4[NH:52][N:51]=[N:50][N:49]=4)=[O:26])=[CH:22][N:21]=3)[N:17]=[C:16]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=3)[CH:15]=2)=[O:13])[CH2:7][CH2:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 178445683HCID 178445683, compoundHCID 178509299HCID 178509299, compound

Product 1

HCID 178445681HCID 178445681, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the intermediate from example 8 step H (65 mg, 0.122 mmol) in DMF (2 mL) was added HOAt (25 mg, 0.184 mmol), amino tetrazole(32 mg, 0.36 mmol), DIEA (64 μL, 0.37 mmol) and EDC (36 mg, 0.184 mmol). The reaction was stirred at 50° C. for 18 hours. The reaction was diluted with ethyl acetate and washed with 1N HCl and saturated NaCl solution. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified on the Gilson reverse phase HPLC to give the title compound. 1H NMR (DMSO, 500 MHz): 9.12 (s, 1H), 8.4 (dd, J=2.0, 9.1 Hz, 2H), 8.18 (d, J=6.6 Hz, 1H), 8.03 (d, J=1.9 Hz, 1H), 7.83 (dd, J=1.9, 8.3 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.53 (s, 1H), 7.24 (d, J=8.2 Hz, 1H), 7.24 (d, J=8.2 Hz, 1H), 5.91 (s, 2H), 3.96 (bm, 1H), 1.83 (d, J=12.3 Hz, 2H), 1.48 (m, 3H), 1.28 (m, 2H), 0.98 (m, 1H), 0.82 (s, 9H). LC-MS=2.71 min; (M+H)=596.2.

Workup

  1. washwashed with 1N HCl and saturated NaCl solution
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on the Gilson reverse phase HPLC

Sources & evidence

ORD record
ord-c48423cc519c4064827e18c79e77baac
Source dataset
uspto-grants-2010_01
Patent number
US07649009B2

Reaction notes

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