Water → N-(2-cyclopropylpropan-2-yl)-2-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246679노트

반응식

HRID 246679 반응식
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:11])[CH:9]=2)[C:4]([C:12]2[N:17]=[C:16]3[C:18]([C:21]([OH:23])=O)=[CH:19][NH:20][C:15]3=[N:14][CH:13]=2)=[N:3]1.Cl.[CH:25]1([C:28]([NH2:31])([CH3:30])[CH3:29])[CH2:27][CH2:26]1.CCN=C=NCCCN(C)C.O>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH:25]1([C:28]([NH:31][C:21]([C:18]2[C:16]3=[N:17][C:12]([C:4]4[C:5]5[C:10](=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=5)[N:2]([CH3:1])[N:3]=4)=[CH:13][N:14]=[C:15]3[NH:20][CH:19]=2)=[O:23])([CH3:30])[CH3:29])[CH2:27][CH2:26]1

참가 물질

7

반응물 4

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 677456142-Cyclopropylpropan-2-amine hydrochlorideHCID 712798782-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

생성물 1

HCID 71280122N-(2-cyclopropylpropan-2-yl)-2-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide수율 25%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

To a stirred mixture of 2-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (80 mg, 0.26 mmol) and 2-cyclopropylpropan-2-amine hydrochloride (53 mg, 0.39 mmol) in DMF (3 mL), was added EDCI (100 mg, 0.52 mmol) followed by DMAP (63 mg, 0.52 mmol). The mixture was stirred at room temperature for 16 hours, and then poured into water (5 mL) and filtered. The crude solid 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: 58% acetonitrile/42% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 88% acetonitrile/12% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give N-(2-cyclopropylpropan-2-yl)-2-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (25 mg, 25%) as a white solid. MS: (M+H)+=389; 1H NMR (300 MHz, DMSO): δ 9.10 (s, 1H), 8.39-8.36 (m, 2H), 7.97 (s, 1H), 7.55 (s, 1H), 7.08 (d, 1H, J=8.1 Hz), Hz), 4.16 (s, 3H), 2.52 (s, 3H), 1.59-1.53 (m, 1H), 1.25 (s, 6H), 0.47-0.43 (m, 4H).

후처리

  1. filtrationfiltered
  2. customThe crude solid was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait58% acetonitrile/42% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 88% acetonitrile/12% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

출처 및 근거

ORD 기록
ord-69a46fa712104ab58d74e2b81b9c80b4
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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