Diisopropylethylamine → 2-amino-N-(3-(3-(3-cyanophenoxy)phenyl)-1-(dimethylamino)-1-oxopropan-2-yl)-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxamide

HRID 449511Notes

Reaction equation

HRID 449511 reaction equation
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.Cl.[NH2:26][CH:27]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([O:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[N:48])[CH:42]=2)[CH:35]=1)[C:28]([N:30]([CH3:32])[CH3:31])=[O:29].[NH2:49][C:50]1[N:59]=[C:58]([N:60]2[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]2)[C:57]2[C:52](=[CH:53][C:54]([C:67](O)=[O:68])=[CH:55][CH:56]=2)[N:51]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[NH2:49][C:50]1[N:59]=[C:58]([N:60]2[CH2:61][CH2:62][N:63]([CH3:66])[CH2:64][CH2:65]2)[C:57]2[C:52](=[CH:53][C:54]([C:67]([NH:26][CH:27]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([O:40][C:41]4[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[N:48])[CH:42]=4)[CH:35]=3)[C:28]([N:30]([CH3:32])[CH3:31])=[O:29])=[O:68])=[CH:55][CH:56]=2)[N:51]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594966492-Amino-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxylic acidHCID 675415352-amino-3-[3-(3-cyanophenoxy)phenyl]-N,N-dimethylpropanamide HCl salt

Product 1

HCID 497790352-amino-N-(3-(3-(3-cyanophenoxy)phenyl)-1-(dimethylamino)-1-oxopropan-2-yl)-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxamideYield 13.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.030 g, 0.078 mmol) was added to a solution of 2-amino-3-[3-(3-cyanophenoxy)phenyl]-N,N-dimethylpropanamide HCl salt (0.045 g) and 2-amino-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxylic acid (0.015 g, 0.052 mmol) in N,N-dimethylformamide (1.0 mL) with N,N-diisopropylethylamine (0.027 mL, 0.16 mmol) at r.t. The reaction was stirred for 1 h. The product was purified without workup by RP-HPLC (pH=2) to give the desired compound (0.004 g, 10%) as a white amorphous solid TFA salt. 1H NMR (400 MHz, DMSO): δ 7.98 (d, 1H), 7.79 (s, 1H), 7.68 (d, 1H), 7.45 (m, 2H), 7.25 (m, 2H), 7.14 (m, 2 h), 7.03 (s, 1H), 6.86 (d, 1H), 5.08 (m, 1H), 4.56 (m, 2H), 3.65 (m, 2H), 3.55 (m, 2H), 3.22 (m, 2H) 2.99 (m, 5H), 2.82 (s, 3H), 2.78 (s, 3H); Analytical LCMS (M+H)+: m/z=579.2.

Workup

  1. customThe product was purified without workup by RP-HPLC (pH=2)

Sources & evidence

ORD record
ord-56097c0cd6ce452888feda04babd315a
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Reaction notes

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