Ammonium → HCID 71526356, 화합물

HRID 1755389노트

반응식

HRID 1755389 반응식
[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]

참가 물질

8

반응물 5

HCID 223AmmoniumHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 71526353HCID 71526353, 화합물

생성물 1

HCID 71526356HCID 71526356, 화합물수율 24%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b063d71d1aa745dc8ccdb6d5cfad846d
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169259B2

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