Triethylamine → (S)-N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-6-methylquinazoline-2-carboxamide
Reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([OH:14])=O)[N:6]=[CH:5]2.[N:15]1[N:16]=[CH:17][N:18]2[CH:23]=[CH:22][N:21]=[C:20]([N:24]3[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25]3)[C:19]=12.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CS(C)=O>[N:15]1[N:16]=[CH:17][N:18]2[CH:23]=[CH:22][N:21]=[C:20]([N:24]3[CH2:28][CH2:27][C@H:26]([NH:29][C:12]([C:7]4[N:6]=[CH:5][C:4]5[C:9](=[CH:10][CH:11]=[C:2]([CH3:1])[CH:3]=5)[N:8]=4)=[O:14])[CH2:25]3)[C:19]=12Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 6-methylquinazoline-2-carboxylic acid (0.040 g, 0.21 mmol, 1.2 eq) and (S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine (0.49 g, 0.18 mmol, 1 eq) in 1 mL of DMSO was added triethylamine (0.10 mL, 0.7 mmol, 4 eq) and HATU (0.075 g, 0.20 mmol, 1.1 eq). After stirring for 1 h at room temperature, the mixture was concentrated and purified by HPLC to afford (S)—N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-6-methylquinazoline-2-carboxamide (0.028 g, 0.07 mmol, 42%). 1H NMR (400 MHz, DMSO) δ 9.62 (s, 1 H), 9.31 (t, J=3.9 Hz, 1 H), 8.08-8.00 (m, 2 H), 8.00-7.92 (m, 1 H), 7.85 (d, J=5.1 Hz, 1 H), 7.29 (d, J=5.0 Hz, 1 H), 4.82-4.70 (m, 1 H), 4.70-3.60 (br, 4 H), 2.56 (s, 3H), 2.40-2.20 (br, 2 H); MS: (ES) m/z calculated for C19H18N8O [M+H]+ 375.2, found 375.
Workup
- concentrationthe mixture was concentrated
- custompurified by HPLC
Sources & evidence
- ORD record
- ord-b9ea2a0335fa4083a405525a1b34f011
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09169261B2
Reaction notes
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