1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(2-cyclopropylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246613

反応式

HRID 246613 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.Cl.[CH:25]1([C:28]([NH2:31])([CH3:30])[CH3:29])[CH2:27][CH2:26]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.O>[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:31][C:28]([CH:25]5[CH2:27][CH2:26]5)([CH3:30])[CH3:29])=[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

9

反応物 5

HCID 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 677456142-Cyclopropylpropan-2-amine hydrochlorideHCID 712800962-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 712802402-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(2-cyclopropylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide収率 28%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒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), 2-cyclopropylpropan-2-amine hydrochloride (0.05 g, 0.37 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. Then HATU (0.114 g, 0.3 mmol) was added, the final reaction mixture was stirred for additional 15 hour. The mixture was poured into 30 mL of water with stirring. After 30 minutes, the mixture was filtered and the filter cake was 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: 35% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 65% acetonitrile/35% 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-(2-cyclopropylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 28%) as a yellow solid. MS: (M+H)+=409; 1H NMR (300 MHz, DMSO): δ 12.81 (s, 1H), 9.04 (s, 1H), 8.41-8.38 (m, 2H), 7.95-7.87 (m, 2H), 7.21 (d, 1H, J=7.2 Hz), 4.15 (s, 3H), 1.53-1.20 (m, 7H), 0.42 (brs, 4H).

後処理

  1. customthe final reaction mixture
  2. stirringwas stirred for additional 15 hour
  3. stirringwith stirring
  4. waitAfter 30 minutes
  5. filtrationthe mixture was filtered
  6. customthe filter cake was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  7. wait35% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 65% acetonitrile/35% 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-2e295972e92d497c9902574da0d6d279
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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