1-Methylpiperazine → Tert-butyl (2-nitro-4-(4-methylpiperazine-1-carbonyl)phenyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-3-tert-butoxycarbonyl-1-methylureido)pyrimidin-4-yl)carbamate

HRID 58188Notes

Reaction equation

HRID 58188 reaction equation
CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.[C:41]([O:45][C:46]([N:48]([C:61]1[CH:66]=[C:65]([N:67]([CH3:90])[C:68]([N:70]([C:83]([O:85][C:86]([CH3:89])([CH3:88])[CH3:87])=[O:84])[C:71]2[C:76]([Cl:77])=[C:75]([O:78][CH3:79])[CH:74]=[C:73]([O:80][CH3:81])[C:72]=2[Cl:82])=[O:69])[N:64]=[CH:63][N:62]=1)[C:49]1[CH:57]=[CH:56][C:52]([C:53](O)=[O:54])=[CH:51][C:50]=1[N+:58]([O-:60])=[O:59])=[O:47])([CH3:44])([CH3:43])[CH3:42]>CN(C=O)C.O.CO.C(Cl)Cl>[N+:58]([C:50]1[CH:51]=[C:52]([C:53]([N:38]2[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]2)=[O:54])[CH:56]=[CH:57][C:49]=1[N:48]([C:61]1[CH:66]=[C:65]([N:67]([CH3:90])[C:68]([N:70]([C:71]2[C:76]([Cl:77])=[C:75]([O:78][CH3:79])[CH:74]=[C:73]([O:80][CH3:81])[C:72]=2[Cl:82])[C:83]([O:85][C:86]([CH3:87])([CH3:88])[CH3:89])=[O:84])=[O:69])[N:64]=[CH:63][N:62]=1)[C:46](=[O:47])[O:45][C:41]([CH3:44])([CH3:42])[CH3:43])([O-:60])=[O:59]

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 121317891HCID 121317891, compound

Product 1

HCID 121324200Tert-butyl (2-nitro-4-(4-methylpiperazine-1-carbonyl)phenyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-3-tert-butoxycarbonyl-1-methylureido)pyrimidin-4-yl)carbamateYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

DIPEA (0.3 mL, 1.62 mmol), HATU (0.515 g, 1.355 mmol) and N-methyl piperazine, 6 (0.09 mL, 0.813 mmol) were added to a solution of 4-((tert-butoxycarbonyl)(6-(3-(tert-butoxycarbonyl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-3-nitrobenzoic acid (0.4 g, 0.542 mmol) in DMF (5 mL) at 0° C. under argon atmosphere. The resulting reaction mixture was then allowed to warm to rt and stirred for 18 h. After completion of the reaction by TLC (MeOH:DCM 1:19), water was added to the reaction mixture. The precipitated crude solid was filtered, dried and purified by silica gel column chromatography to obtain the title compound (0.27 g, yield: 61%) as a solid. MS (ESI): 819.1 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. additionwas added to the reaction mixture
  3. customThe precipitated crude solid
  4. filtrationwas filtered
  5. customdried
  6. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-d730a7481b994dd1b89c28b6b4625599
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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