1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(2-phenylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246588

반응식

HRID 246588 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[C:24]1([C:30]([NH2:33])([CH3:32])[CH3:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCN=C=NCCCN(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:33][C:30]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)([CH3:32])[CH3:31])=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 68509CumylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712800962-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 712798052-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(2-phenylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 18%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 2-phenylpropan-2-amine (0.05 g, 0.37 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), HATU (0.114 g, 0.3 mmol) and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF were stirred at room temperature overnight. The solvent was removed under reduced pressure at 70° C. The residue was triturated with 5 mL of water and then 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: 60% acetonitrile/40% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 80% acetonitrile/20% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(2-phenylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.017 g, 18%) as a yellow solid. MS: (M+H)+=445; 1H NMR (300 MHz, DMSO): δ 12.89 (s, 1H), 9.13 (s, 1H), 8.46-8.43 (m, 2H), 8.38-8.37 (m, 1H), 8.00 (s, 1H), 7.51-7.49 (m, 2H), 7.34-7.16 (m, 4H), 4.20 (s, 3H), 1.86 (s, 6H).

후처리

  1. customThe solvent was removed under reduced pressure at 70° C
  2. customThe residue was triturated with 5 mL of water
  3. custompurified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  4. wait60% acetonitrile/40% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 80% acetonitrile/20% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

출처 및 근거

ORD 기록
ord-2392f51f0015450abc2600fb6b938124
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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