Diisopropylethylamine → (S)-N-methyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide

HRID 2097785노트

반응식

HRID 2097785 반응식
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][N:20]=4)[CH2:15][CH2:14]3)[CH:10]=[N:11][C:5]=2[N:4]2[CH2:28][CH2:29][CH2:30][C@@H:3]12.C[CH2:32][N:33](C(C)C)C(C)C.Cl.CN.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO>[CH3:32][NH:33][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][C:19]([N:16]2[CH2:17][CH2:18][N:13]([CH2:12][C:9]3[CH:10]=[N:11][C:5]4[N:4]5[CH2:28][CH2:29][CH2:30][C@H:3]5[C:2](=[O:1])[NH:7][C:6]=4[CH:8]=3)[CH2:14][CH2:15]2)=[N:20][CH:21]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58324509(S)-6-(4((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinic acid

생성물 1

HCID 58324370(S)-N-methyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide수율 51%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

(S)-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinic acid (100 mg, 0.245 mmol) was suspended in DMF (1.5 mL) and DIPEA (0.3 mL) was added followed by methylamine hydrochloride (27 mg, 0.400 mmol) and HATU (200 mg, 0.526 mmol). The reaction mixture was stirred at ambient temperature for 4 h and diluted with MeOH (2 mL). The solution was purified using HPCL (25-95% acetonitrile in water, NH4HCO3 buffered). The fractions were concentrated in vacuo and the resulting residue was crystallized with MeOH-water (1:5, 15 mL) to afford the title compound as an off-white solid (52.3 mg, 51%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.80-2.03 (m, 3 H) 2.09-2.25 (m, 1 H) 2.41 (br. s., 4 H) 2.74 (d, J=4.29 Hz, 3 H) 3.34-3.44 (m, 3 H) 3.46-3.64 (m, 5 H) 3.92-4.05 (m, 1 H) 6.82 (d, J=9.09 Hz, 1 H) 6.99 (d, 1 H) 6.93-7.04 (m, 1 H) 7.61 (s, 1 H) 7.91 (dd, J=8.97, 2.15 Hz, 1 H) 8.17-8.23 (m, 1H) 8.56 (d, J=1.77 Hz, 1 H) 10.44 (s, 1 H); [M+H] calc'd for C22H27N7O2, 422; found, 422.

후처리

  1. customThe solution was purified
  2. concentrationThe fractions were concentrated in vacuo
  3. customthe resulting residue was crystallized with MeOH-water (1:5, 15 mL)

출처 및 근거

ORD 기록
ord-5879e169db0f428bbb37cef2234329fd
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450323B2

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