(S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-(tetrahydro-2H-pyran-4-ylcarbamoyl)isoquinolin-3-yl)ethylcarbamate → (S)-3-(1-aminoethyl)-8-chloro-N-(tetrahydro-2H-pyran-4-yl)isoquinoline-1-carboxamide

HRID 518269Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([C:12](=[O:20])[NH:13][CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[N:9][C:8]([C@@H:21]([NH:23]C(=O)OCC1C3C=CC=CC=3C3C1=CC=CC=3)[CH3:22])=[CH:7]2>N1CCOCC1>[NH2:23][C@H:21]([C:8]1[N:9]=[C:10]([C:12]([NH:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:20])[C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[CH:3][C:2]=2[Cl:1])[CH3:22]

Participants

Conditions

Temperature: 45 °C

Procedure

(S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-(tetrahydro-2H-pyran-4-ylcarbamoyl)isoquinolin-3-yl)ethylcarbamate (351) (20.0 g, 36.0 mmol, 1.0 eq) was suspended in morpholine (200 mL), and then stirred at 40-50° C. for 1 h. The reaction mixture was concentrated in vacuo and then 1,4-dioxane (200 mL) was added to the residue. The mixture was concentrated in vacuo. The operation was repeated for 3-4 times. The residue was purified by flash column chromatography on silica gel (2-10% MeOH-DCM) to afford (S)-3-(1-aminoethyl)-8-chloro-N-(tetrahydro-2H-pyran-4-yl)isoquinoline-1-carboxamide (352).

Workup

concentrationThe reaction mixture was concentrated in vacuo
addition1,4-dioxane (200 mL) was added to the residue
concentrationThe mixture was concentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (2-10% MeOH-DCM)

Sources & evidence

ORD record: ord-5d67c3ba02374b94a7d609af491d3fa9
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115141B2

Reaction notes

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