Diisopropylethylamine → tert-butyl (3-(6-ethyl-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

HRID 527414Notes

Reaction equation

HRID 527414 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)[CH:7]=[CH:6][C:4]=1[NH2:5].[CH2:17]([C:19]1[C:31](=[O:32])[N:30]([C:33]2[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH:36]=[CH:37][CH:38]=2)[C:22]2[N:23]=[C:24](S(C)=O)[N:25]=[CH:26][C:21]=2[CH:20]=1)[CH3:18].CCN(C(C)C)C(C)C>C(O)CCC>[CH2:17]([C:19]1[C:31](=[O:32])[N:30]([C:33]2[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH:36]=[CH:37][CH:38]=2)[C:22]2[N:23]=[C:24]([NH:5][C:4]3[CH:6]=[CH:7][C:8]([N:10]4[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15]4)=[CH:9][C:3]=3[O:2][CH3:1])[N:25]=[CH:26][C:21]=2[CH:20]=1)[CH3:18]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 201362532-Methoxy-4-(4-methylpiperazin-1-yl)anilineHCID 86732026tert-butyl (3-(6-ethyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

Product 1

HCID 86732027tert-butyl (3-(6-ethyl-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamateYield 77.4%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
85 °C

Procedure

2-Methoxy-4-(4-methylpiperazin-1-yl)aniline (Combi-Blocks Inc, San Diego, Calif., catalog #: SS-3744; 386 mg, 1.75 mmol), tert-butyl (3-(6-ethyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (6a) (680 mg, 1.59 mmol) were treated with tort-butanol (10 mL) and DIEA (0.69 mL, 3.97 mmol) and heated to 85° C. for 14 h in a 250 mL round-bottomed flask with a reflux condenser. The reaction mixture was concentrated under reduced pressure (rotary evaporator) and the crude solid was purified by chromatography on a silica gel column (1-20% MeOH in DCM) affording tert-butyl (3-(6-ethyl-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (6b; 717 mg, 1.23 mmol, 77% yield) as a light brown film. m/z (ESI, +ve ion) 585.9 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure (rotary evaporator)
  2. customthe crude solid was purified by chromatography on a silica gel column (1-20% MeOH in DCM)

Sources & evidence

ORD record
ord-497f1f8a36b94079819e5d726c10f2ab
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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