Tert-Butylamine → N-tert-butyl-2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246775노트

반응식

HRID 246775 반응식
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[N:9]=[C:8]2[C:15]1[N:16]=[C:17]2[C:23]([C:24]([OH:26])=O)=[CH:22][NH:21][C:18]2=[N:19][CH:20]=1)(=[O:4])=[O:3].[CH3:27][C:28]([NH2:31])([CH3:30])[CH3:29].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:28]([NH:31][C:24]([C:23]1[C:17]2=[N:16][C:15]([C:8]3[C:7]4[C:11](=[CH:12][CH:13]=[C:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:6]=4)[N:10]([CH3:14])[N:9]=3)=[CH:20][N:19]=[C:18]2[NH:21][CH:22]=1)=[O:26])([CH3:30])([CH3:29])[CH3:27]

참가 물질

8

반응물 5

HCID 6385Tert-ButylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712795392-(5-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 71280042N-tert-butyl-2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide수율 8.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 2-(5-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (75 mg, 0.20 mmol), 2-methylpropan-2-amine (15 mg, 0.20 mmol), HOBt (108 mg, 0.80 mmol), EDCI (153 mg, 0.80 mmol) and DIPEA (103 mg, 0.80 mmol) in DMF (6 mL) was stirred at room temperature for 15 hours, then water (30 mL) was added, product extracted with EtOAc (3×30 mL), organics combined dried with sodium sulfate, filtered and concentrated under reduced pressure and residue 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: 30% methanol/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 50% methanol/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give N-tert-butyl-2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (7 mg, 8.1%) as a white solid. LCMS: (M+H)+=427; 1H NMR (300 MHz, CD3OD): δ 9.08 (s, 1H), 8.99 (s, 1H), 8.33 (s, 1H), 8.01 (d, 1H, J=8.7 Hz), 7.90 (d, 1H, J=8.7 Hz), 4.28 (s, 3H), 3.17 (s, 3H), 1.57 (s, 9H).

후처리

  1. extractionproduct extracted with EtOAc (3×30 mL)
  2. dry with materialorganics combined dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure and residue
  5. custompurified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  6. wait30% methanol/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 50% methanol/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.

출처 및 근거

ORD 기록
ord-43cdca4a3cfb446488c61363eaa850d2
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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