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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-(4-Fluoro-2-methyl-phenylamino)-1,6-dimethyl-7-{3-[(1-methyl-1-oxo-phosphinan-4-yl)carbonylamino]-propenyl}-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

HRID 1863914
ノート
印刷プレビュー

反応式

HRID 1863914 の反応式
[NH2:1][CH2:2][CH:3]=[CH:4][C:5]1[NH:6][C:7](=[O:29])[C:8]2[C:9]3[N:18]([CH3:19])[C:17]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=4[CH3:28])=[N:16][C:10]=3[CH:11]=[CH:12][C:13]=2[C:14]=1[CH3:15].[CH3:30][P:31]1(=[O:40])[CH2:36][CH2:35][CH:34]([C:37](O)=[O:38])[CH2:33][CH2:32]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(N(CC)CC)C.CN(C)C=O>[F:27][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:17]2[N:18]([CH3:19])[C:9]3[C:8]4[C:7](=[O:29])[NH:6][C:5]([CH:4]=[CH:3][CH2:2][NH:1][C:37]([CH:34]5[CH2:35][CH2:36][P:31]([CH3:30])(=[O:40])[CH2:32][CH2:33]5)=[O:38])=[C:14]([CH3:15])[C:13]=4[CH:12]=[CH:11][C:10]=3[N:16]=2)=[C:22]([CH3:28])[CH:23]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579733021-Methyl-1-oxo-1lambda5-phosphinane-4-carboxylic acidHCID 668324547-(3-Amino-propenyl)-2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

生成物 1

HCID 668326372-(4-Fluoro-2-methyl-phenylamino)-1,6-dimethyl-7-{3-[(1-methyl-1-oxo-phosphinan-4-yl)carbonylamino]-propenyl}-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one
収率 26%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8471Triethylamine溶媒2 回

実験手順

To scintillation vial with a magnetic stir-bar was added 7-(3-amino-propenyl)-2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (68 mg, 173 mmol), followed by dimethylformamide (DMF) (1.0 mL) and triethylamine (TEA) (0.25 mL). To a separate scintillation vial was added 1-methyl-1-oxo-1λ5-phosphinane-4-carboxylic acid (130 mg, 0.74 mmol, mixture of cis/trans isomers), HATU (300 mg, 0.79 mmol), and DMF (2.0 mL), followed by TEA (0.25 mL). The solution was sonicated until most of the solids were dissolved. A solution of the activated ester (1.0 mL, or roughly half) was transferred to the solution of amine and stirred for 2.5 hours at room temperature, after which time the starting material was completely consumed as determined by LC-MS. The reaction mixture was quenched by addition of water (0.5 mL), then acidified with TFA. The mixture was filtered (syringe membrane filter) and purified directly by reverse-phase HPLC to provide 2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-7-{3-[(1-methyl-1-oxo-phosphinan-4-yl)carbonylamino]-propenyl}-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (24.9 mg, 26%) as a mixture of cis/trans isomers. 1H NMR (400 MHz, d6-DMSO) δ 11.12 (s, 1H), 10.55 (s, 1H), 8.21-8.17 (m, 1H), 7.74 (d, J=8.6Hz, 1H), 7.69 (d, J=8.6Hz, 1H), 7.55 (dd, J1=5.9 Hz, J2=9.0 Hz, 1H), 7.27 (td, J1=2.7 Hz, J2=8.6 Hz, 1H), 6.66 (d, J=15 Hz, 1H), 6.55-6.49 (m, 1H), 4.18 (s, 3H), 3.92 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 2.35-2.30 (m, 1H), 2.08-1.90 (m, 6H), 1.78-1.65 (m, 2H), 1.52-1.47 (m, 3H); ESMS m/z: found, 550 (M+1)+.

後処理

  1. customThe solution was sonicated until most of the solids
  2. dissolutionwere dissolved
  3. customafter which time the starting material was completely consumed
  4. customThe reaction mixture was quenched by addition of water (0.5 mL)
  5. filtrationThe mixture was filtered
  6. filtration(syringe membrane filter)
  7. custompurified directly by reverse-phase HPLC

出典と根拠

ORDレコード
ord-c9f816cb25aa4c77924cee028c4428fc
出典データセット
uspto-grants-2009_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07625880B2

反応ノート

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