2-Amino-2-methyl-1-propanol → 2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246646ノート

反応式

HRID 246646 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:20](O)=[O:21])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[NH2:23][C:24]([CH3:28])([CH3:27])[CH2:25][OH:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:20]([NH:23][C:24]([CH3:28])([CH3:27])[CH2:25][OH:26])=[O:21])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 118072-Amino-2-methyl-1-propanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712803892-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

生成物 1

HCID 712798692-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide収率 3.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 2-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (140 mg, 0.446 mmol), 2-amino-2-methylpropan-1-ol (48 mg, 0.536 mmol), EDCI (256 mg, 1.338 mmol), HOBt (181 mg, 1.338 mmol) and DIPEA (173 mg, 1.338 mmol) in dry DMF (5 mL) was stirred for 16 hours at room temperature. Water (5 mL) was added and the formed precipitate was separated by filtration, then 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 are: 35% acetonitrile/65% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min) to afford 2-(6-chloro-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (6 mg, 3%) as a white solid. LCMS: (M+H)+=385; 1H NMR (300 MHz, DMSO+D2O): δ 9.09 (s, 1H), 8.52 (d, 1H, J=8.4 Hz), 8.31 (s, 1H), 7.72 (s, 1H), 7.25 (d, 1H, J=9.0 Hz), 3.59 (s, 2H), 1.41 (s, 6H).

後処理

  1. customthe formed precipitate was separated by filtration
  2. customwas purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait35% acetonitrile/65% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min

出典と根拠

ORDレコード
ord-6ef945dcc079487a8681827e9161edb4
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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