Lithium borohydride → N-(adamantan-1-ylmethyl)-2-(hydroxymethyl)pyrazolo[1,5-a]pyridine-4-carboxamide

HRID 2039778Notes

Reaction equation

[Li+].[BH4-].C([O:5][C:6]([C:8]1[CH:30]=[C:11]2[C:12]([C:16](=[O:29])[NH:17][CH2:18][C:19]34[CH2:28][CH:23]5[CH2:24][CH:25]([CH2:27][CH:21]([CH2:22]5)[CH2:20]3)[CH2:26]4)=[CH:13][CH:14]=[CH:15][N:10]2[N:9]=1)=O)C>C1COCC1>[C:19]12([CH2:18][NH:17][C:16]([C:12]3[C:11]4[N:10]([N:9]=[C:8]([CH2:6][OH:5])[CH:30]=4)[CH:15]=[CH:14][CH:13]=3)=[O:29])[CH2:26][CH:25]3[CH2:27][CH:21]([CH2:22][CH:23]([CH2:24]3)[CH2:28]1)[CH2:20]2

Participants

Conditions

Temperature: 50 °C

Procedure

A 2.0 M solution of LiBH4 in THF (5.8 mL) is added dropwise to a solution of 4-[(adamantan-1-ylmethyl)carbamoyl]pyrazolo[1,5-a]pyridine-2-carboxylic acid ethyl ester (2.01 g, 5.27 mmol) and THF (50 mL) at 0° C. under N2. After 10 min, the ice bath is removed. After 3 h, additional 2.0 M solution of LiBH4 in THF (2.0 mL) is added. After 4 h, sat. aq. NH4Cl is added dropwise. The volatiles are removed under reduced pressure. H2O (20 mL) is added and the solids are collected by filtration. The solids are slurried in MeOH (75 mL) and warmed to 50° C. for 4 h. The volatiles are removed under reduced pressure to afford the title compound as a light tan solid. 1H NMR (300 MHz, CDCl3) δ: 8.58 (ddd, 1H), 7.56 (dd, 1H), 6.92 (t, 1H), 6.90 (s, 1H), 4.80 (s, 2H), 3.12 (s, 2H), 1.96-2.04 (m, 3H), 1.62-1.84 (m, 12H). LC-MS m/z (M+H+): 340.3; RT=1.27 min.

Workup

customthe ice bath is removed
waitAfter 3 h
additionadditional 2.0 M solution of LiBH4 in THF (2.0 mL) is added
waitAfter 4 h
additionsat. aq. NH4Cl is added dropwise
customThe volatiles are removed under reduced pressure
additionH2O (20 mL) is added
filtrationthe solids are collected by filtration
customThe volatiles are removed under reduced pressure

Sources & evidence

ORD record: ord-73f9a11f921d490380cfd79e9d2e3e7b
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580812B2

Reaction notes

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