Hydrochloric Acid → HCID 68630764, compound

HRID 1893633Notes

Reaction equation

HRID 1893633 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:29]([CH3:32])([CH3:31])[CH3:30])[C:10]([N:12]1[CH2:16][CH:15]([OH:17])[CH2:14][CH:13]1[C:18]([NH:20][C:21]1([C:26]([OH:28])=[O:27])[CH2:23][CH:22]1[CH2:24][CH3:25])=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Cl[C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[C:42]([O:50][CH2:51][CH3:52])[N:41]=1.Cl>CS(C)=O>[C:1]([O:5][C:6]([NH:8][CH:9]([C:29]([CH3:31])([CH3:30])[CH3:32])[C:10]([N:12]1[CH2:16][CH:15]([O:17][C:40]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=[C:42]([O:50][CH2:51][CH3:52])[N:41]=2)[CH2:14][CH:13]1[C:18]([NH:20][C:21]1([C:26]([OH:28])=[O:27])[CH2:23][CH:22]1[CH2:24][CH3:25])=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 574451481-Chloro-3-ethoxyisoquinolineHCID 68616376HCID 68616376, compound

Product 1

HCID 68630764HCID 68630764, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1-{[1-(2-tert-Butoxycarbonylamino-3,3-dimethylbutyryl)-4-hydroxypyrrolidine-2-carbonyl]-amino}-2-ethyl-cyclopropanecarboxylic acid (See Example 33), 0.21 g, 0.46 mmol) was diluted in DMSO (4 mL) and treated with potassium tert-butoxide (0.26 g, 2.3 mmol) at rt for 30 min. 1-Chloro-3-ethoxyisoquinoline (0.100 g, 0.48 mmol) was added and the solution allowed to age overnight. Icewater was added, followed by 1M HCl until the solution reaches pH 3. Extraction with EtOAc was followed by washing of the combined organics with brine and drying over anhydrous Na2SO4 prior to concentration in vacuo. The resulting residue was purified by preparatory HPLC to produce 0.127 g (42%) of 1-{[1-(2-tert-Butoxycarbonylamino-3,3-dimethyl-butyryl)-4-(3-ethoxy-isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-ethyl-cyclopropanecarboxylic acid as a white solid. LCMS found 626.90 [M+].

Workup

  1. customallowed to age overnight
  2. additionIcewater was added
  3. extractionExtraction with EtOAc
  4. washby washing of the combined organics with brine
  5. dry with materialdrying over anhydrous Na2SO4
  6. concentrationto concentration in vacuo
  7. customThe resulting residue was purified by preparatory HPLC

Sources & evidence

ORD record
ord-fd41db2c406a4b8fa0d5658aaff2fb97
Source dataset
uspto-grants-2013_08
Patent number
US08513186B2

Reaction notes

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