Tetrahydrofuran → HCID 66654007, compound

HRID 2036242Notes

Reaction equation

HRID 2036242 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@H:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([OH:32])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(O[N:41]1[N:49]=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.NN.C1COCC1>CN(C=O)C.C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@H:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([NH:41][NH2:49])=[O:32])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66654114HCID 66654114, compound

Product 1

HCID 66654007HCID 66654007, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1-(2-carboxymethoxy-5-chloro-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (165 mg, 0.36 mmol, 1.0 eq.) in DMF (0.9 mL), TBTU (138 mg, 0.43 mmol, 1.2 eq.) and DIPEA (0.19 mL, 1.08 mmol, 3.0 eq.) were added in sequence. The resulting reaction mixture was stirred at r.t. for 15 min. Then 1M hydrazine in anhydrous THF (1.99 mL, 1.99 mmol, 5.6 eq.) was added at 0° C. (exothermic). The resulting mixture was stirred at r.t. for 18 hours. The reaction mixture was diluted with DCM and then washed with sat. aq. NaHCO3 soln. The aq. phase was extracted once with DCM. The comb. org. phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, basic conditions) and evaporated to give the desired product as a brown foam.

Workup

  1. customThe resulting reaction mixture
  2. stirringThe resulting mixture was stirred at r.t. for 18 hours
  3. washwashed with sat. aq. NaHCO3 soln
  4. extractionThe aq. phase was extracted once with DCM
  5. dry with materialphases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep
  9. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, basic conditions) and evaporated

Sources & evidence

ORD record
ord-6c868df8387f4d6db614fbc0f0197ded
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

Loading…