Diisopropylamine → HCID 178432477, 화합물

HRID 1909053

반응식

HRID 1909053 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](C2C=CC3N(CN(C)C)C=NC=3C=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[O:30][C:31](=O)[C:32]1[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[C:34]([C:40]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=[N:42][C:41]=2[CH3:50])[CH:33]=1.[Li+].C[CH:54]([N-:56][CH:57]([CH3:59])[CH3:58])C.C([NH:63]C(C)C)(C)C.[CH2:67]([Li])[CH2:68][CH2:69]C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]([C:68]2[CH:69]=[CH:59][C:57]3[NH:56][C:54]([C:31](=[O:30])[C:32]4[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[C:34]([C:40]5[C:49]6[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=6)[CH:43]=[N:42][C:41]=5[CH3:50])[CH:33]=4)=[N:63][C:58]=3[CH:67]=2)=[O:15])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 5

HCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamide2회HCID 665994174-(1-Dimethylaminomethyl-1H-benzoimidazole-5-carbonyl)-piperazine-1-carboxylic acid tert-butyl esterHCID 665996304-Cyano-3-(3-methyl-isoquinolin-4-yl)-benzoic acid methyl esterHCID 178418339Butyllithium

생성물 1

HCID 178432477HCID 178432477, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

To a stirring solution of 2 (76 mg, 0.195 mmol) and 4 (62 mg, 0.205 mmol, 1.05 eq) in THF (5 mL) at −78° C. was added freshly prepared 1M LDA dropwise (Prepared from Diisopropylamine and 2.5M n-Butyl Lithium in Hexanes). Upon addition of LDA, an orange color formed and stayed throughout the reaction. After 1.5 hr of stirring at −78° C. the reaction was quenched with 50% aqueous Acetic Acid (5 mL) and the reaction mixture warmed to room temperature. The reaction mixture was diluted with Ethyl Acetate (50 mL) and neutralized using 28-30% Ammonium Hydroxide (aq) until pH˜9. The aqueous layer was extracted one additional time with Ethyl Acetate and the combined organics washed with brine, dried (Na2SO4), and concentrated to a yellow crystalline solid. The crude mixture was purified using Biotage MPLC system (25S column size, 0-10% Methanol/CH2Cl2 over 70CV), giving title compound as an off white solid (60 mg, 0.100 mmol, 51%). 1H NMR (DMSO-d6, 400 MHz): δ 13.9 (s, 1H), δ 9.44 (s, 1H), δ 8.84-8.82 (d, 1H), δ 8.57 (s, 1H), δ 8.39-8.37 (d, 1H), δ 8.27-8.25 (d, 1H), δ 7.90 (bs, 1H), 7.79-7.64 (m, 3H), 7.50-7.35 (m, 1H), δ 7.30-7.28 (d, 1H), δ 3.70-3.30 (m, 8H), δ 2.46 (s, 3H), δ 1.41 (s, 9H); LRMS (m/z): 601 (M+H), 545

후처리

  1. customan orange color formed
  2. customstayed throughout the reaction
  3. customwas quenched with 50% aqueous Acetic Acid (5 mL)
  4. temperaturethe reaction mixture warmed to room temperature
  5. additionThe reaction mixture was diluted with Ethyl Acetate (50 mL)
  6. extractionThe aqueous layer was extracted one additional time with Ethyl Acetate
  7. washthe combined organics washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated to a yellow crystalline solid
  10. customThe crude mixture was purified

출처 및 근거

ORD 기록
ord-5055429c4eb64ff0b7f34e80a5d4b1ca
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598217B2

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