Diisopropylethylamine → HCID 78319002, compound

HRID 527440Notes

Reaction equation

HRID 527440 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:17][CH3:18].C(N(C(C)C)CC)(C)C.[CH3:28][C:29]1[C:38]2[CH:37]=[N:36][C:35](S(C)=O)=[N:34][C:33]=2[N:32]([C:42]2[CH:43]=[C:44]([NH:48][C:49](=[O:52])[CH:50]=[CH2:51])[CH:45]=[CH:46][CH:47]=2)[C:31](=[O:53])[CH:30]=1>C(O)(C)(C)C.O1CCOCC1>[C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:35]3[N:36]=[CH:37][C:38]4[C:29]([CH3:28])=[CH:30][C:31](=[O:53])[N:32]([C:42]5[CH:43]=[C:44]([NH:48][C:49](=[O:52])[CH:50]=[CH2:51])[CH:45]=[CH:46][CH:47]=5)[C:33]=4[N:34]=3)=[C:3]([O:17][CH3:18])[CH:4]=2)[CH2:9][CH2:10]1)(=[O:16])[CH3:15]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 552327371-(4-(4-aMino-3-Methoxyphenyl)piperazin-1-yl)ethanoneHCID 86732024N-(3-(5-methyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

Product 1

HCID 78319002HCID 78319002, compoundYield 34.7%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 1-(4-(4-amino-3-methoxyphenyl)piperazin-1-yl)ethanone (20b; 351 mg, 1.40 mmol), diisopropylethylamine (0.41 mL, 2.34 mmol) and N-(3-(5-methyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (5b; 288 mg, 0.78 mmol) in tert-butanol (2 mL) and dioxane (1 mL) in a sealed glass tube was heated in an oil bath at 110° C. for 72 h. It was concentrated under reduced pressure. The brown residue was stirred in 5 mL of ether for 10 min. The liquid was decanted; the remaining solid was loaded on a silica gel column and eluted with 2-10% MeOH in DCM followed by 5% 2 M NH3 in MeOH in DCM to give the title compound (20) (150 mg, 34% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (1H, s), 8.81 (1H, s), 8.12 (1H, s), 7.88 (1H, d, J=8.0 Hz), 7.42-7.61 (2H, m), 7.28 (1H, d, J=9.0 Hz), 6.98 (1H, d, J=7.8 Hz), 6.56 (1H, m), 6.44 (1H, m), 6.33 (1H, s), 6.24 (1H, m), 6.04 (1H, br. s.), 5.75 (1H, m), 3.78 (3H, s), 3.56 (4H, m), 3.04 (2H, m), 2.97 (2H, m), 2.46 (3H, s), 2.03 (3H, s). m/z (ESI, +ve ion) 554.3 (M+H)+.

Workup

  1. concentrationIt was concentrated under reduced pressure
  2. customThe liquid was decanted
  3. washeluted with 2-10% MeOH in DCM

Sources & evidence

ORD record
ord-ab5776cc2393404e987c81e368a82ba6
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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