Aluminium lithium hydride → HCID 57947769, compound

HRID 340967Notes

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-16f1b4da909f44a4827f21b250aa44d9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895582B2

Reaction notes

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