1,4-diazepane-1-carbaldehyde → HCID 86652278, compound

HRID 1409205Notes

Reaction equation

HRID 1409205 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[N:25]1([CH:32]=[O:33])[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>CN(C=O)C.CS(C)=O.CO>[CH:32]([N:25]1[CH2:31][CH2:30][CH2:29][N:28]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:27][CH2:26]1)=[O:33]

Participants

6

Reactant 2

HCID 70066561,4-diazepane-1-carbaldehydeHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 86652278HCID 86652278, compoundYield 77.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 86 mg, 0.25 mmol) and 1,4-diazepane-1-carbaldehyde (97 mg, 0.75 mmol) in DMF (1.0 mL) was stirred at 100° C. for 2 h. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC (25-35% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (84.4 mg, 77%). 1H NMR (DMSO-d6) δ: 10.86 (s, 1H), [1:1 ratio of rotamers: 8.09 (s, 1H); 7.93 (s, 1H)], 7.98 (d, J=8.3 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.14 (d, J=2.8 Hz, 1H), 6.16 (s, 1H), 4.25-4.39 (m, 3H), 3.55-3.71 (m, 4H), 3.46-3.54 (m, 1H), 2.37 (s, 3H), 1.97-2.09 (m, 1H), 1.86-1.97 (m, 1H), 1.45 (s, 6H); ESI-MS: m/z 437.3 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (25-35% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-616cc23b0bd34905ae82e2bf222ef922
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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