1H-Indole-2-carboxylic acid, 1-methyl- → HCID 16116975, compound

HRID 2355083Notes

Reaction equation

HRID 2355083 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([OH:13])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[NH2:47][C:48]1[CH:49]=[CH:50][C:51]([CH3:77])=[C:52]([CH:76]=1)[C:53]([NH:55][C:56]1[CH:57]=[N:58][C:59]([NH:62][C:63]2[CH:68]=[CH:67][C:66]([N:69]3[CH2:74][CH2:73][N:72]([CH3:75])[CH2:71][CH2:70]3)=[CH:65][CH:64]=2)=[N:60][CH:61]=1)=[O:54]>CN(C=O)C.CO.CS(C)=O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([NH:47][C:48]1[CH:49]=[CH:50][C:51]([CH3:77])=[C:52]([C:53](=[O:54])[NH:55][C:56]2[CH:57]=[N:58][C:59]([NH:62][C:63]3[CH:64]=[CH:65][C:66]([N:69]4[CH2:70][CH2:71][N:72]([CH3:75])[CH2:73][CH2:74]4)=[CH:67][CH:68]=3)=[N:60][CH:61]=2)[CH:76]=1)=[O:13]

Participants

7

Reactant 4

HCID 276951H-Indole-2-carboxylic acid, 1-methyl-HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16118190HCID 16118190, compound

Product 1

HCID 16116975HCID 16116975, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

In a 16×120 mm resealable pyrex tube, 1-methyl-1H-indole-2-carboxylic acid (0.11 g, 0.62 mmol), HATU (0.24 g, 0.62 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.17 ml, 0.96 mmol) were taken up in DMF (5 mL) and allowed to stir at rt for 30 min. 5-amino-2-methyl-N-(2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)benzamide 30 (0.200 g, 0.48 mmol) was added and the mixture was stirred at rt overnight. The crude reaction mixture was taken up in minimal MeOH/DMSO and purified by preparative HPLC (acidic Shimadzu: 15-85% (0.1% TFA in CH3CN) in H2O over 20 min). Clean fractions were combined and neutralized with saturated NaHCO3 then extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated to afford 1-methyl-N-(4-methyl-3-((2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)carbamoyl)phenyl)-1H-indole-2-carboxamide 31 as a tan solid. MS m/z found 575.2 [MH+]; calc. for C33H34N8O2=574.28.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. customThe crude reaction mixture
  3. custompurified by preparative HPLC (acidic Shimadzu: 15-85% (0.1% TFA in CH3CN) in H2O over 20 min)
  4. extractionthen extracted with CH2Cl2
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-5cf20c937a5c4258a16a3026cc29fba2
Source dataset
uspto-grants-2010_07
Patent number
US07754717B2

Reaction notes

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