Diisopropylethylamine → (R)-2-amino-4-(4-methylpiperazin-1-yl)-N-[1-(naphthalen-2-yl)ethyl]quinazoline-7-carboxamide

HRID 449340Notes

Reaction equation

HRID 449340 reaction equation
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[NH2:25][C:26]1[N:35]=[C:34]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[C:33]2[C:28](=[CH:29][C:30]([C:43](O)=[O:44])=[CH:31][CH:32]=2)[N:27]=1.C(N(CC)C(C)C)(C)C.[CH:55]1[C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH:58]=[CH:57][C:56]=1[C@H:65]([NH2:67])[CH3:66]>CN(C)C=O>[NH2:25][C:26]1[N:35]=[C:34]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[C:33]2[C:28](=[CH:29][C:30]([C:43]([NH:67][C@@H:65]([C:56]3[CH:57]=[CH:58][C:59]4[C:64](=[CH:63][CH:62]=[CH:61][CH:60]=4)[CH:55]=3)[CH3:66])=[O:44])=[CH:31][CH:32]=2)[N:27]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1798835(1R)-1-(naphthalen-2-yl)ethan-1-amineHCID 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 acid

Product 1

HCID 49779436(R)-2-amino-4-(4-methylpiperazin-1-yl)-N-[1-(naphthalen-2-yl)ethyl]quinazoline-7-carboxamideYield 48.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (40 mg, 0.1 mmol) was added to a solution of 2-amino-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxylic acid (20 mg, 0.07 mmol) in N,N-dimethylformamide (1 mL) and N,N-diisopropylethylamine (24 μL, 0.14 mmol). The reaction mixture was stirred for 10 minutes, and then (1R)-1-(2-naphthyl)ethanamine (24 mg, 0.14 mmol) was added. The crude reaction mixture stirred for 18 h. at r.t. and then was purified on RP-HPLC (pH=2) to afford the title product (15 mg, 27%) as a TFA salt as an off white amorphous solid. 1H NMR (300 MHz, DMSO): δ 1.52 (d, 3H), 2.82 (s, 3H), 3.22 (m, 2H), 3.65 (m, 4H), 4.65 (m, 2H), 5.32 (m, 1H), 7.44 (m, 2H), 7.54 (dd, 1H), 7.76-7.86 (m, 5H), 7.92 (d, 1H), 8.02 (d, 1H); Analytic LCMS (M+H)+: m/z=441.2.

Workup

  1. customThe crude reaction mixture
  2. stirringstirred for 18 h. at r.t.
  3. customwas purified on RP-HPLC (pH=2)

Sources & evidence

ORD record
ord-95d996f50f6c4466ad59236479d2bddb
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Reaction notes

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