Aniline → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-phenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246600

反応式

HRID 246600 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=O)=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[O:23])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712800962-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 712796492-(6-chloro-1-methyl-1H-indazol-3-yl)-N-phenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 29%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), aniline (0.05 g, 0.54 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature for 5 hours. And then HATU (0.114 g, 0.3 mmol) was added, the final reaction mixture was stirred for 15 hours. The solvent was removed under reduced pressure at 70° C. The residue was triturated with water and then purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 65% acetonitrile/35% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 72% acetonitrile/28% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-phenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 29%) as a white solid. MS: (M+H)+=403; 1H NMR (300 MHz, DMSO): δ 10.21 (s, 1H), 9.12 (s, 1H), 8.63-8.58 (m, 2H), 8.42 (brs, 2H), 8.04 (s, 1H), 7.83-7.80 (m, 2H), 7.49-7.43 (m, 2H), 7.30 (d, 1H, J=8.7 Hz), 7.17 (d, 1H, J=7.2 Hz), 4.21 (s, 3H).

後処理

  1. customthe final reaction mixture
  2. stirringwas stirred for 15 hours
  3. customThe solvent was removed under reduced pressure at 70° C
  4. customThe residue was triturated with water
  5. custompurified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  6. wait65% acetonitrile/35% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 72% acetonitrile/28% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

出典と根拠

ORDレコード
ord-58ec797298ba492a96a5a76568928180
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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