Dimethylformamide → 2-amino-N-[(1S)-1-cyano-2-(4-isopropoxyphenyl)ethyl]-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxamide

HRID 449482Notes

Reaction equation

HRID 449482 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]([OH:45])=O)=[CH:31][CH:32]=2)[N:27]=1.CN(C)C=O.C(N(CC)C(C)C)(C)C.[NH2:60][C@@H:61]([CH2:64][C:65]1[CH:70]=[CH:69][C:68]([O:71][CH:72]([CH3:74])[CH3:73])=[CH:67][CH:66]=1)[C:62]#[N:63]>>[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:60][C@H:61]([C:62]#[N:63])[CH2:64][C:65]3[CH:70]=[CH:69][C:68]([O:71][CH:72]([CH3:74])[CH3:73])=[CH:67][CH:66]=3)=[O:45])=[CH:31][CH:32]=2)[N:27]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59496533(2S)-2-amino-3-(4-isopropoxyphenyl)propanenitrileHCID 594966492-Amino-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxylic acid

Product 1

HCID 594967412-amino-N-[(1S)-1-cyano-2-(4-isopropoxyphenyl)ethyl]-4-(4-methylpiperazin-1-yl)quinazoline-7-carboxamideYield 12.1%

Procedure

N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (42 mg, 0.11 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 (2 mL, 20 mmol) and N,N-diisopropylethylamine (24 uL, 0.14 mmol). The reaction was stirred for 10 min., and the (2S)-2-amino-3-(4-isopropoxyphenyl)propanenitrile (28 mg, 0.14 mmol) was added. The reaction was stirred for 1 h. at r.t., and was purified by RP-HPLC (pH=2) to afford the desired product (4 mg, 10%) as a white solid TFA salt. Analytical LCMS (M+H)+: m/z=474.1.

Workup

  1. stirringThe reaction was stirred for 1 h. at r.t.
  2. customwas purified by RP-HPLC (pH=2)

Sources & evidence

ORD record
ord-406659184fdf4497a91ec61282183172
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Reaction notes

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