Tetrahydrofuran → (R)-methyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)propanoate

HRID 468765Notes

Reaction equation

HRID 468765 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.O1CCCC1.C[CH2:24][O:25][C:26]([C@@H:28](O)[CH3:29])=[O:27].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(OCC)(=O)C>[CH:15]1([C:13]([NH:12][C:7]2[N:8]=[CH:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([O:1][C@H:28]([CH3:29])[C:26]([O:25][CH3:24])=[O:27])[CH:11]=3)=[O:14])[CH2:16][CH2:17]1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 92831(L)-ethyl lactate2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 67975011N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 68095268(R)-methyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)propanoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide (68.7 mg, 0.301 mmol) in tetrahydrofuran (3.0 mL, 37 mmol) was added ethyl L-(−)-lactate (44 uL, 0.39 mmol) and triphenylphosphine (108.4 mg, 0.4133 mmol), followed by dropwise addition of diethyl azodicarboxylate (62 uL, 0.39 mmol). The resulting mixture was stirred at room temperature for 1 hour, and then ethyl L-(−)-lactate (13 uL, 0.11 mmol) and diethyl azodicarboxylate (19 uL, 0.12 mmol) were added. After an additional 2.5 hours, the reaction mixture was poured into ethyl acetate, washed with water and brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude material was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-80% ethyl acetate in heptanes) to provide a quantitative yield of (R)-methyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)propanoate. LCMS (ESI): M+H=329.2.

Workup

  1. waitAfter an additional 2.5 hours
  2. washwashed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude material was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-80% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-591c1d57833d4b7c90d87b03069b444d
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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