Cesium carbonate → 7-[4-(6-cyclopropylmethoxy-1-oxo-1H-isoquinolin-2-yl)-2-fluorophenyl]-2,7-diaza-spiro[4.4]nonane-2-carboxylic acid tert-butyl ester

HRID 69446Notes

Reaction equation

HRID 69446 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:32]=[CH:31][C:30]5[C:25](=[CH:26][CH:27]=[C:28]([OH:33])[CH:29]=5)[C:24]4=[O:34])=[CH:19][C:18]=3[F:35])[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:37][CH:38]1[CH2:40][CH2:39]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN1C(=O)CCC1>O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:32]=[CH:31][C:30]5[C:25](=[CH:26][CH:27]=[C:28]([O:33][CH2:37][CH:38]6[CH2:40][CH2:39]6)[CH:29]=5)[C:24]4=[O:34])=[CH:19][C:18]=3[F:35])[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 81503BromomethylcyclopropaneHCID 68991198HCID 68991198, compound

Product 1

HCID 689915857-[4-(6-cyclopropylmethoxy-1-oxo-1H-isoquinolin-2-yl)-2-fluorophenyl]-2,7-diaza-spiro[4.4]nonane-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 7-[2-fluoro-4-(6-hydroxy-1-oxo-1H-isoquinolin-2-yl)-phenyl]-2,7-diaza-spiro[4.4]nonane-2-carboxylic acid tert-butyl ester (250 mg), bromomethyl-cyclopropane (70 mg), cesium carbonate (170 mg) and NMP (5 mL) was heated for 4 hours at 60° C. The cooled reaction mixture was distributed between ethyl acetate and water. The organic phase was dried over magnesium sulfate and concentrated. The raw product was purified by preparative HPLC.

Workup

  1. customThe cooled reaction mixture
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe raw product was purified by preparative HPLC

Sources & evidence

ORD record
ord-d747d454e7e14b3c817af86d040ab60b
Source dataset
uspto-grants-2014_09
Patent number
US08822495B2

Reaction notes

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