Diisopropylethylamine → HCID 68757534, compound

HRID 387566Notes

Reaction equation

HRID 387566 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[N:12]1([C:18]2[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]3[NH:26][N:27]=[CH:28][C:19]=23)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.[C:29]([O:33][C:34]([N:36]([CH:49]([CH3:51])[CH3:50])[CH2:37][C@H:38]([C:42]1[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=1)[C:39](O)=[O:40])=[O:35])([CH3:32])([CH3:31])[CH3:30].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:48][C:45]1[CH:46]=[CH:47][C:42]([C@H:38]([C:39]([N:15]2[CH2:16][CH2:17][N:12]([C:18]3[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]4[NH:26][N:27]=[CH:28][C:19]=34)[CH2:13][CH2:14]2)=[O:40])[CH2:37][N:36]([CH:49]([CH3:50])[CH3:51])[C:34](=[O:35])[O:33][C:29]([CH3:31])([CH3:30])[CH3:32])=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 68757503HCID 68757503, compound

Product 1

HCID 68757534HCID 68757534, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIEA (d 0.742; 0.102 mL, 0.585 mmol) was added to a solution of 4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile dihydrochloride (0.0661 g, 0.219 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.050 g, 0.146 mmol, see Example B) and TBTU (0.0564 g, 0.176 mmol) in DCM (1 mL) and stirred at room temperature for 18 hours. The mixture was directly loaded onto a silica column and purified by chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-cyano-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate as a solid. The solid was dissolved in DCM (1 mL), and TFA (0.2 mL) was added. The mixture was stirred at room temperature for 1 hour and concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give (S)-4-(4-(2-(4-chlorophenyl)-3-(isopropylamino)propanoyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile dihydrochloride (0.043 g, 56%). MS APCI (+) m/z 452.1 detected.

Workup

  1. custompurified by chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-52975eda96ca466c9c60c08049154b7a
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

Loading…