Ammonium → HCID 71526356、化合物

HRID 1755389ノート

反応式

HRID 1755389 の反応式
[C:1]([CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[C:18]4[N:19]([CH:32]=[CH:33][N:34]=4)[N:20]=[C:21]([C:23]4[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=4)[C:26](O)=[O:27])[CH:22]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH4+].CC[N:38]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>O1CCOCC1.ClCCl>[C:1]([CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[C:18]4[N:19]([CH:32]=[CH:33][N:34]=4)[N:20]=[C:21]([C:23]4[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=4)[C:26]([NH2:38])=[O:27])[CH:22]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:6]1)([CH3:2])([CH3:4])[CH3:3]

参加物

8

反応物 5

HCID 223AmmoniumHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 71526353HCID 71526353、化合物

生成物 1

HCID 71526356HCID 71526356、化合物収率 24%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 3-(8-(6-(3-tert-butylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (25 mg, 0.106 mmol), 0.5 M ammonium in dioxane solution (2 mL), EDCI (43 mg, 0.22 mmol), HOBT (30 mg, 0.22 mmol), Et3N (23 mg, 0.22 mmol) and dichloromethane (2 mL) was stirred at room temperature for 16 h. The solution was concentrated in vacuo and purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give 3-(8-(6-(3-tert-butylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (6 mg, 24%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.79 (s, 1H), 8.91 (s, 1H), 8.47 (s, 1H), 8.31 (s, 1H), 8.16-8.02 (m, 3H), 7.79 (s, 1H), 7.63 (t, 1H, J=7.6 Hz), 7.52-7.47 (m, 2H), 6.72 (d, 1H, J=7.8 Hz), 6.11 (d, 1H, J=8.4 Hz), 3.72-3.66 (m, 1H), 3.52-3.40 (m, 2H), 3.12 (t, 1H, J=10.0 Hz), 2.13-1.94 (m, 2H), 1.78-1.74 (m, 1H), 0.86 (s, 9H). LC-MS: [M+H]+, 456, tR=1.72 min, HPLC: 99.11% at 214 nm, 99.64% at 254 nm, tR=4.22 min.

後処理

  1. concentrationThe solution was concentrated in vacuo
  2. custompurified by prep-HPLC (Gemini 5u C18 150×21.2 mm
  3. waitgradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min

出典と根拠

ORDレコード
ord-b063d71d1aa745dc8ccdb6d5cfad846d
出典データセット
uspto-grants-2015_10
特許番号
US09169259B2

反応ノート

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