O-Phenylenediamine → HCID 44612630, compound

HRID 1645733Notes

Reaction equation

HRID 1645733 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[C:8]([O:10][CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:7]=[CH:6][N:5]2[C:19]=1[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]2[CH:35]=[CH:34][C:30]([C:31]([OH:33])=O)=[CH:29][CH:28]=2)[N:21]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:60]1([NH2:67])[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=1[NH2:66].CCN(C(C)C)C(C)C>CN(C=O)C.O.C(#N)C>[NH2:66][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][C:60]=1[NH:67][C:31](=[O:33])[C:30]1[CH:34]=[CH:35][C:27]([NH:26][C:22]2[N:21]=[C:20]([C:19]3[N:5]4[CH:6]=[CH:7][C:8]([O:10][CH2:11][CH2:12][N:13]5[CH2:18][CH2:17][O:16][CH2:15][CH2:14]5)=[CH:9][C:4]4=[N:3][C:2]=3[CH3:1])[CH:25]=[CH:24][N:23]=2)=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 7243O-Phenylenediamine2×HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 66772169HCID 66772169, compound

Product 1

HCID 44612630HCID 44612630, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a mixture of methyl 4-(4-(7-chloro-2-methylH-imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzoate (100 mg, 0.25 mmol), KOtBu (86 mg, 0.76 mmol) in NMP (2 mL), and 2-morpholin-4-yl-ethanol (0.16 mL, 1.3 mmol) were added and heated in a microwave (Emry's Optimizer) at 170° C. for 10 minutes. The reaction mixture was then diluted with water and acetonitrile and purified by preparative HPLC affording 4-{4-[2-methyl-7-(2-morpholin-4-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-benzoic acid after lyophilization. MS found for C25H26N6O4 as (M+H)+ 475.05. To the above carboxylic acid (59 mg, 0.124 mmol) in DMF (3 mL), were added HATU (71 mg, 0.186 mmol), 1,2-phenylenediamine (27 mg, 0.25 mmol), and DIPEA (0.07 mL, 0.372 mmol) and stirred at room temperature for 16 hours. Additional 1,2-phenylenediamine (50 mg, 0.46 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (0.2 mL) were added and stirred at room temperature for 4 hours. The reaction mixture was diluted with water and acetonitrile and directly purified by preparative HPLC affording the title compound, after lyophilization. MS found for C31H32N8O3 as (M+H)+ 565.08. 1H NMR (400 MHz, dmso-d6): δ 10.04 (brs, 1H); 9.62 (m, 2H); 8.61 (d, J=4.8 Hz, 1H); 7.92 (d, J=8.8 Hz, 2H); 7.84 (d, J=8.8 Hz, 2H); 7.23 (s, 1H); 7.15 (d, J=6.0 Hz, 2H); 6.98-6.69 (m, 5H); 4.51 (m, 2H); 3.74-3.38 (m, 10H); 2.62 (s, 3H).

Workup

  1. stirringstirred at room temperature for 4 hours
  2. customdirectly purified by preparative HPLC

Sources & evidence

ORD record
ord-bf68c7444da34ba5b661a0884a22b026
Source dataset
uspto-grants-2012_02
Patent number
US08124764B2

Reaction notes

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