Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclobutyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246573

반응식

HRID 246573 반응식
[F: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.CN(C(ON1N=[N:39][C:34]2[CH:35]=[CH:36][CH:37]=N[C:33]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CC1(N)CCC1>CN(C=O)C>[F: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:39][C:34]5([CH3:33])[CH2:37][CH2:36][CH2:35]5)=[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

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14988399(1-Methylcyclobutyl)amineHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 712799512-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclobutyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 13.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (59 mg, 0.19 mmol), HATU (91.20 mmol, 0.24 mmol) and DIPEA (49 mg, 0.38 mmol) in 6 mL of DMF, 1-methylcyclobutanamine (21.00 mg, 0.25 mmol) was added in one portion at room temperature and the reaction mixture was stirred for 16 hours. The solvent was evaporated at 80° C. under reduced pressure and the residue 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: 48% acetonitrile/52% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclobutyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (10 mg, 13.7%) as an off-white solid. MS: (M+H)+=379; 1H NMR (300 MHz, DMSO): δ 12.82 (s, 1H), 9.10 (s, 1H), 8.47-8.38 (m, 2H), 8.24 (s, 1H), 7.70 (d, 1H, J=8.7 Hz), 7.17 (t, 1H, J=9.2 Hz), 4.15 (s, 3H), 2.54-2.45 (m, 2H), 2.15-2.13 (m, 2H), 1.96-1.88 (m, 2H), 1.62 (s, 3H).

후처리

  1. customThe solvent was evaporated at 80° C. under reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait48% acetonitrile/52% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

출처 및 근거

ORD 기록
ord-f1956236cfac4415ac093ff83ff27d61
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

연결된 노트

불러오는 중…