Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 59344942、化合物

HRID 19156ノート

反応式

HRID 19156 の反応式
[Li+].[CH3:2][N:3]([CH3:26])[C:4]1[C:5]([F:25])=[C:6]([CH:22]=[CH:23][CH:24]=1)[O:7][C:8]1[CH2:12][N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14]([O-])=[O:15])[C:10](=[O:21])[CH:9]=1.[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH2:39])=[N:35]2)[CH2:30][O:29]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH:39][C:14](=[O:15])[C@@H:13]([N:11]3[CH2:12][C:8]([O:7][C:6]4[CH:22]=[CH:23][CH:24]=[C:4]([N:3]([CH3:2])[CH3:26])[C:5]=4[F:25])=[CH:9][C:10]3=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[N:35]2)[CH2:30][O:29]1

参加物

5

反応物 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 67504629(s)-2-[4-(3-Dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid lithium salt

生成物 1

HCID 59344942HCID 59344942、化合物収率 51.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid lithium salt (0.257 g, 0.73 mmol) in N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.160 g, 0.81 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.91 g, 4.32 mmol). The mixture was stirred at room temperature overnight and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with a saturated sodium chloride solution and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 10% to 75% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.200 g, 51%) as a yellow solid: HR-ES-MS m/z calculated for C27H36FN5O5 [M+H]+ 530.2773, observed 530.2771, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.25 (s, 3H), 1.31 (d, J=3.0 Hz, 3H), 1.38-1.50 (m, 1H), 1.50-1.65 (m, 1H), 1.69-1.85 (m, 1H), 2.82 (s, 6H), 3.74 (dd, J=8.3, 5.9 Hz, 1H), 4.01 (dd, J=8.5, 6.3 Hz, 1H), 4.04-4.15 (m, 2H), 4.20 (d, J=18.4 Hz, 1H), 4.29-4.43 (m, 1H), 4.58 (d, J=18.4 Hz, 1H), 4.86 (s, 1H), 4.87-4.95 (m, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.79-6.98 (m, 2H), 7.12 (t, J=8.5 Hz, 1H), 7.61 (br. s., 1H), 10.80 (s, 1H).

後処理

  1. customthe solvents were evaporated
  2. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  3. customthe organic layer separated
  4. washThe organic layer was washed with a saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customThe solvents were evaporated
  7. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 10% to 75% ethyl acetate/hexanes) which

出典と根拠

ORDレコード
ord-03edb212b591483080725095a1f7a2f7
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

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