Triethylamine → Pemrametostat

HRID 880340노트

반응식

HRID 880340 반응식
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C@H:12]([OH:24])[CH2:13][N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:9])[CH:3]=1.[NH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32](=[O:34])[CH3:33])[CH2:28][CH2:27]1.CCN(CC)CC>CC(O)C>[C:32]([N:29]1[CH2:30][CH2:31][CH:26]([NH:25][C:2]2[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C@H:12]([OH:24])[CH2:13][N:14]3[CH2:23][CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:15]3)=[O:9])[CH:3]=2)[CH2:27][CH2:28]1)(=[O:34])[CH3:33]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 49624771-(4-Aminopiperidin-1-yl)ethan-1-oneHCID 90241529(S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide

생성물 1

HCID 90241742Pemrametostat수율 130,573.398%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

The solution of (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide (190 g, 0.55 mmol) and 1-(4-aminopiperidin-1-yl)ethanone (78 g), Et3N (100 g, 1 mol) in i-PrOH (2000 mL) was stirred at 60° C. for 16 h, at which time LCMS showed completed conversion. The mixture was concentrated and the residue was purified by flash chromatography to give the crude product. Four batches were run in parallel and produced a combined crude product weight of 482 g. This crude was further purified on preparative HPLC to give the title compound (325 g, >98% purity, free base form). 1H NMR (400 MHz, MeOD-d4) 8.26 (s, 1H), 7.15-7.02 (m, 5H), 4.46 (m, 1H), 4.15-4.07 (m, 2H), 3.88 (m, 1H), 3.74 (s, 2H), 3.53 (m, 2H), 3.33 (m, 1H), 2.95-2.86 (m, 5H), 2.68 (m, 2H), 2.14-2.01 (m, 5H), 1.48-1.42 (m, 2H); LCMS (m/z): 453.3 [M+H]+

후처리

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by flash chromatography
  3. customto give the crude product
  4. customproduced a combined crude product weight of 482 g
  5. customThis crude was further purified on preparative HPLC

출처 및 근거

ORD 기록
ord-1c63cf638e364d7998a2a6c5d7a5b151
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993555B2

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