Dimethylamine → HCID 78318937, compound

HRID 527426Notes

Reaction equation

HRID 527426 reaction equation
Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N:13]2[C:18]3[N:19]=[C:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([N:30]5[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]5)=[CH:26][C:25]=4[O:37][CH3:38])[N:21]=[CH:22][C:17]=3[CH:16]=[CH:15][C:14]2=[O:39])[CH:8]=1)=[O:5].[CH3:40][NH:41][CH3:42]>>[CH3:40][N:41]([CH3:42])[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N:13]2[C:18]3[N:19]=[C:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([N:30]5[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]5)=[CH:26][C:25]=4[O:37][CH3:38])[N:21]=[CH:22][C:17]=3[CH:16]=[CH:15][C:14]2=[O:39])[CH:8]=1)=[O:5]

Participants

3

Reactant 2

HCID 674DimethylamineHCID 86732034HCID 86732034, compound

Product 1

HCID 78318937HCID 78318937, compoundYield 76.7%

Conditions

Temperature
50 °C

Procedure

3-Chloro-N-(3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)propanamide (57 mg, 0.086 mmol) was treated with dimethylamine (2.0 M in THF, 2.00 mL, 4.00 mmol) and stirred at 50° C. for 90 min then stirred at RT for 72 h. The reaction mixture was then purified by chromatography on silica gel on an ISCO Combiflash RF (24 g Redisep HP (Gold), using a gradient of 0-20% 2M NH3/MeOH in DCM) affording 3-(dimethylamino)-N-(3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)propanamide (44.6 mg, 0.066 mmol, 76% yield) as a yellow-orange amorphous foam. m/z (ESI, +ve ion) 557.0 (M+H)+. 1H NMR (400 MHz, MeOH-d4) δ ppm 8.71 (1H, s), 7.92 (1H, d, J=9.4 Hz), 7.57-7.61 (1H, m), 7.56 (1H, s), 7.44 (1H, d, J=7.8 Hz), 7.06 (1H, d, J=8.0 Hz), 6.58 (1H, d, J=2.5 Hz), 6.53 (1H, d, J=9.4 Hz): 6.12 (1H, br. s.), 3.88 (3H, s), 3.10-3.19 (4H, m), 2.77 (2H, q, J=6.7 Hz), 2.63-2.68 (4H, m), 2.57-2.62 (2H, m), 2.39 (3H, s), 2.33 (6H, s).

Workup

  1. stirringthen stirred at RT for 72 h
  2. customThe reaction mixture was then purified by chromatography on silica gel on an ISCO Combiflash RF (24 g Redisep HP (Gold)

Sources & evidence

ORD record
ord-6cf39df0792a4a41a3d20549263d062c
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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