Diisopropylethylamine → (8-Bromo-5-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-((1R,2R)-2-phenyl-cyclopropyl)-methanone
Reaction equation
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[Br:45][C:46]1[CH:47]=[CH:48][C:49]([F:56])=[C:50]2[C:55]=1[CH2:54][NH:53][CH2:52][CH2:51]2>C(Cl)Cl.O>[Br:45][C:46]1[CH:47]=[CH:48][C:49]([F:56])=[C:50]2[C:55]=1[CH2:54][N:53]([C:10]([C@@H:8]1[CH2:9][C@H:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:12])[CH2:52][CH2:51]2Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of (1R,2R)-2-phenyl-cyclopropanecarboxylic acid (389 mg, 2.4 mmol, 1.2 eq.) in DCM (10 mL), DIPEA (1.37 ml, 8 mmol, 4.0 eq.) and TBTU (771 mg, 2.4 mmol, 1.2 eq.) were added in sequence. The resulting solution was stirred at r.t. for 30 minutes. Then 8-bromo-5-fluoro-1,2,3,4-tetrahydro-isoquinoline hydrochloride (533 mg, 2.0 mmol, 1.0 eq.) was added and the resulting mixture was stirred at r.t. for 18 hours. The reaction mixture was poured in water (50 mL). The mixture was extracted with DCM (2×30 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 30 fractions of 45 mL, Heptane to Heptane+50% AcOEt) to yield the title compound as a yellow oil.
Workup
- stirringthe resulting mixture was stirred at r.t. for 18 hours
- extractionThe mixture was extracted with DCM (2×30 mL)
- dry with materialphases were dried over MgSO4
- concentrationconcentrated in vacuo
- customThe residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 30 fractions of 45 mL, Heptane to Heptane+50% AcOEt)
Sources & evidence
- ORD record
- ord-6c3e4846abf14749afee70754d8ec99f
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09255090B2
Reaction notes
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