Cesium carbonate → HCID 66653612, compound

HRID 2036202Notes

Reaction equation

HRID 2036202 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].CNC1CCCCC1NC.[CH2:22]([O:29][C:30]([N:32]1[CH2:41][CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]1[C:42]1[CH:47]=[C:46](Br)[CH:45]=[CH:44][C:43]=1[O:49][CH2:50][C:51]([O:53]CC)=[O:52])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C.[Cu]I>[CH2:22]([O:29][C:30]([N:32]1[CH2:41][CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]1[C:42]1[CH:47]=[C:46]([N:1]2[CH:5]=[CH:4][N:3]=[N:2]2)[CH:45]=[CH:44][C:43]=1[O:49][CH2:50][C:51]([OH:53])=[O:52])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[CH2:22]([O:29][C:30]([N:32]1[CH2:41][CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]1[C:42]1[CH:47]=[C:46]([N:2]2[N:3]=[CH:4][CH:5]=[N:1]2)[CH:45]=[CH:44][C:43]=1[O:49][CH2:50][C:51]([OH:53])=[O:52])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 5510741-N,2-N-dimethylcyclohexane-1,2-diamineHCID 66654234HCID 66654234, compoundHCID 178418936HCID 178418936, compound

Product 2

HCID 66653612HCID 66653612, compoundHCID 66654170HCID 66654170, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

1H-1,2,3-triazole (23 μL, 0.400 mmol, 2.00 eq.), copper (I) iodide (1.9 mg, 0.010 mmol, 0.05 eq.), cesium carbonate (130. mg, 0.400 mmol, 2.00 eq.) and N,N′-dimethyl-cyclohexane-1,2-diamine (7 μL, 0.040 mmol, 0.20 eq.) were added at r.t. to a solution of (±)-1-(5-bromo-2-ethoxycarbonylmethoxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (105 mg, 0.200 mmol, 1.00 eq.) in DMF (0.1 mL) in a microwave tube. The tube was flushed with N2, sealed, and heated to 120° C. for 60 hours. The reaction mixture was diluted with water and washed with AcOEt. The remaining aqueous phase was acidified with 1N aq. HCl and extracted with AcOEt (3×). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The crude residue, redissolved in DMF (1.2 mL), was purified by prep. HPLC (column: Atlantis, 19×50 mm, 5 um, UV/MS, acidic conditions) to give (±)-1-(2-carboxymethoxy-5-[1,2,3]triazol-1-yl-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (LC-MS 1FA: tR=0.75 min; [M+H]+=485.2) and (±)-1-(2-carboxymethoxy-5-[1,2,3]triazol-2-yl-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (LC-MS 1FA: tR=0.85 min; [M+H]+=485.1).

Workup

  1. customThe tube was flushed with N2
  2. customsealed
  3. additionThe reaction mixture was diluted with water
  4. washwashed with AcOEt
  5. extractionextracted with AcOEt (3×)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude residue, redissolved in DMF (1.2 mL)
  10. customwas purified by prep

Sources & evidence

ORD record
ord-ab7fadb5c2944b388f361edb3310997c
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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