Aluminium lithium hydride → HCID 57947769, compound

HRID 409829Notes

Reaction equation

[F:1][C:2]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:3]=1[CH2:4][NH:5][C:6](=[O:31])[N:7]([C@H:9]([CH2:16][O:17][C:18](=[O:30])[NH:19][C:20]1[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:10][CH2:11][C:12](OC)=[O:13])[CH3:8].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:29]=[C:20]([NH:19][C:18](=[O:30])[O:17][CH2:16][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]2[CH:32]=[CH:33][CH:34]=[C:35]([F:36])[C:2]=2[F:1])=[O:31])[CH2:10][CH2:11][CH2:12][OH:13])[N:21]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (S)-methyl 4-(3-(2,3-difluorobenzyl)-1-methylureido)-5-(isoquinolin-3-ylcarbamoyloxy)pentanoate (1.0 g, 2.0 mmol) in THF (10 mL) was added LAH (2.0 M in THF, 1.5 mL, 3.0 mmol) at 0° C. and stirred at 0° C. for 20 min. The mixture was quenched with H2O (0.12 mL), NaOH (3 N, 0.12 mL), and H2O (0.36 mL) and the resulting suspension was stirred at RT for 30 min and filtered. The filtrate was concentrated and the residue was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-5-hydroxypentyl isoquinolin-3-ylcarbamate (0.52 g, 55%). LRMS (M+H+) m/z 473.2.

Workup

customThe mixture was quenched with H2O (0.12 mL), NaOH (3 N, 0.12 mL), and H2O (0.36 mL)
stirringthe resulting suspension was stirred at RT for 30 min
filtrationfiltered
concentrationThe filtrate was concentrated
customthe residue was purified on silica gel column
additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record: ord-70f256a1297f4525af80ead73465628a
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759374B2

Reaction notes

Loading…