Diisopropylethylamine → Methyl 4-{3-[({[2-amino-4-(4-methylpiperazin-1-yl)quinazolin-7-yl]carbonyl}amino)methyl]phenoxy}benzoate

HRID 449517Notes

Reaction equation

HRID 449517 reaction equation
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.Cl.[NH2:26][CH2:27][C:28]1[CH:29]=[C:30]([CH:42]=[CH:43][CH:44]=1)[O:31][C:32]1[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=1.[NH2:45][C:46]1[N:55]=[C:54]([N:56]2[CH2:61][CH2:60][N:59]([CH3:62])[CH2:58][CH2:57]2)[C:53]2[C:48](=[CH:49][C:50]([C:63](O)=[O:64])=[CH:51][CH:52]=2)[N:47]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[NH2:45][C:46]1[N:55]=[C:54]([N:56]2[CH2:57][CH2:58][N:59]([CH3:62])[CH2:60][CH2:61]2)[C:53]2[C:48](=[CH:49][C:50]([C:63]([NH:26][CH2:27][C:28]3[CH:29]=[C:30]([CH:42]=[CH:43][CH:44]=3)[O:31][C:32]3[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=3)=[O:64])=[CH:51][CH:52]=2)[N:47]=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 67541602Methyl 4-[3-(aminomethyl)phenoxy]benzoate-hcl

Product 1

HCID 59496728Methyl 4-{3-[({[2-amino-4-(4-methylpiperazin-1-yl)quinazolin-7-yl]carbonyl}amino)methyl]phenoxy}benzoateYield 73%

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 methyl 4-[3-(aminomethyl)phenoxy]benzoate-HCl (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=10) to give the desired product (0.020 g, 50%) as a white amorphous solid. 1H NMR (400 MHz, DMSO): δ 9.16 (m, 1H), 7.89 (d, 2H), 7.70 (m, 2H), 7.36 (m, 2H), 7.14 (d, 1H), 6.99 (d, 2H), 6.95 (m, 2H), 6.39 (bs, 2H), 4.44 (d, 2H), 3.75 (s, 3H), 3.50 (bs, 4H), 3.29 (s, 4H), 2.18 (s, 3H); Analytical LCMS (M+H)+: m/z=527.0.

Workup

  1. customThe product was purified without workup by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-fe5e9e5d694f43308d21f781ebcb93a3
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Reaction notes

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