2,6-Dimethylaniline → HCID 57662956, compound

HRID 2402503Notes

Reaction equation

HRID 2402503 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]=[C:12]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=4)[N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH3:30][C:31]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:32]=1[NH2:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O.CC(N(C)C)=O>[CH3:30][C:31]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:32]=1[NH:33][C:25](=[O:26])[C:24]1[CH:23]=[CH:22][C:21]([NH:20][C:12]2[N:11]=[C:10]([C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][CH:2]=[CH:3]4)[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 68962,6-DimethylanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57663028HCID 57663028, compound

Product 1

HCID 57662956HCID 57662956, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

To a round bottomed flask containing 4-(4-(1H-indol-5-yl)quinazolin-2-ylamino)-benzoic acid (428 mg, 1.13 mmol) was added 2,6-dimethylaniline (137 mg, 1.13 mmol), HATU (428 mg, 1.13), Hunig's base (400 μL, 2.3 mmol), and dimethylacetamide (4 mL). The stirred mixture was heated to at 50° C. for 14 h, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with 5% aqueous lithium chloride and saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The crude material was purified by preparative reverse phase HPLC to afford N-(2,6-dimethylphenyl)-4-{[4-(1H-indol-5-yl)quinazolin-2-yl]amino}benzamide as a yellow solid (24 mg, 5%). 1H NMR (400 MHz, DMSO-d6): δ 11.45 (s, 1H), 10.23 (s, 1H), 9.60 (s, 1H), 8.19 (d, 2H), 8.02 (m, 4H), 7.83 (m, 2H), 7.62 (m, 2H), 7.51 (m, 1H), 7.41 (m, 1H), 7.13 (s, 3H), 6.63 (m, 1H), 2.20 (s, 6H). MS (EI) C31H25N5O: 484.2 (MH+).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic extracts were washed with 5% aqueous lithium chloride and saturated sodium chloride
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated on a rotary evaporator
  6. customThe crude material was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-c4be763c440f4b2ab84ede9b166e2619
Source dataset
uspto-grants-2014_08
Patent number
US08796294B2

Reaction notes

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