Methylamine → (R)-2-(2-(2,4-Dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-N,4-dimethylpentanamide

HRID 2092870노트

반응식

HRID 2092870 반응식
[CH3:1][O:2][C:3]1[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:4]=1[CH2:5][N:6]1[CH2:14][C:13]2[C:12]([F:15])=[C:11]([NH:16][C@H:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:18](O)=[O:19])[N:10]=[C:9]([C:25]3[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=3)[C:8]=2[C:7]1=[O:31].Cl.CN.C[CH2:42][N:43](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN.CCN=C=NCCCN(C)C.Cl.C1C=C2N=NN(O)C2=CC=1.O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:4]=1[CH2:5][N:6]1[CH2:14][C:13]2[C:12]([F:15])=[C:11]([NH:16][C@H:17]([CH2:21][CH:22]([CH3:23])[CH3:24])[C:18]([NH:43][CH3:42])=[O:19])[N:10]=[C:9]([C:25]3[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=3)[C:8]=2[C:7]1=[O:31]

참가 물질

9

반응물 7

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochloride2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58317621(R)-2-(2-(2,4-Dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanoic acid

생성물 1

HCID 67238387(R)-2-(2-(2,4-Dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-N,4-dimethylpentanamide수율 95%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

A solution of (R)-2-(2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanoic acid (48 mg, 0.094 mmol), methylamine hydrochloride (31.7 mg, 0.469 mmol) and DIPEA (49.2 μL, 0.281 mmol) in DMF (1 mL) was stirred at RT for 10 min. HATU (71.4 mg, 0.188 mmol) was added and the mixture was stirred at RT for 1 h, after which HPLC showed about 80% starting material remained. Additional methylamine (58.4 μL, 0.469 mmol, 33% in EtOH) was added, which resulted in little conversion of the starting material. The solvent was stripped off and the residue was dissolved in DMF (1 mL). To this solution was added EDCI hydrochloride (54.0 mg, 0.281 mmol), HOBT monohydrate (43.1 mg, 0.281 mmol), and methylamine hydrochloride (31.7 mg, 0.469 mmol). The reaction mixture was heated to 60° C. for 4 h. HPLC subsequently showed the reaction mixture contained 95% of desired product. The reaction mixture was allowed to cool to RT. Water (50 mL) was added and the mixture was extracted with DCM (3×50 mL). The organic layers were collected, dried over Na2SO4, filtered, and the solvent was stripped to dryness via rotary evaporation to yield the title compound, which was used without further purification. [M+H] calc'd for C27H33FN6O4, 525. found, 525.

후처리

  1. customwhich resulted in little conversion of the starting material
  2. temperatureThe reaction mixture was heated to 60° C. for 4 h

출처 및 근거

ORD 기록
ord-0cc9bdc960064949a31464d73b875687
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440689B2

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