Hydrochloric Acid → HCID 58010006, 화합물

HRID 2204584노트

반응식

HRID 2204584 반응식
S([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25](C(OCC5C6C=CC=CC=6C6C5=CC=CC=6)=O)[CH2:24]4)=[CH:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+].Cl.[C:49]([C:51]1([C:54]([OH:56])=O)[CH2:53][CH2:52]1)#[N:50].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O1CCOCC1.CN(C=O)C>[CH:13]1[C:14]2[N:19]3[C:20]([C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([C:54]([C:51]5([C:49]#[N:50])[CH2:53][CH2:52]5)=[O:56])[CH2:24]4)=[CH:21][N:22]=[C:18]3[CH:17]=[N:16][C:15]=2[NH:11][CH:12]=1

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 27332591-Cyanocyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58010039HCID 58010039, 화합물

생성물 1

HCID 58010006HCID 58010006, 화합물수율 9.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매2회

반응 조건

온도
100 °C

실험 절차

To a solution of (R)-(9H-fluoren-9-yl)methyl 3-(3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)piperidine-1-carboxylate (0.20 g, 0.32 mmol) in 1,4-dioxane (3 mL) was added aqueous NaOH (2 N, 0.97 mL, 1.9 mmol). The reaction mixture was heated at about 100° C. for about 3 h before it was allowed to cool to ambient temperature. The reaction was neutralized with 4N HCl in 1,4-dioxane (0.5 mL) and was concentrated under reduced pressure. To the residue was added MeCN (25 mL) before it was concentrated under reduced pressure. This procedure was repeated before the addition of 1-cyanocyclopropanecarboxylic acid (0.072 g, 0.65 mmol), HATU (0.111 g, 0.291 mmol) and DMF (2 mL) followed by DIEA (0.170 mL, 0.971 mmol). After stirring at room temperature for about 3 h, the reaction was partitioned between EtOAc (2×50 mL) and aqueous NaHCO3 (50 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude reaction was purified by RP-HPLC (Table 2, Method j). The combined product-containing fractions were concentrated under reduced pressure to remove MeCN and then lyophilized to give (R)-1-(3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)piperidine-1-carbonyl)cyclopropanecarbonitrile as a white solid (0.010 g, 9%): LC/MS (Table 2, Method a) Rt=1.67 min; MS m/z: 335 (M+H)+.

후처리

  1. temperatureto cool to ambient temperature
  2. concentrationwas concentrated under reduced pressure
  3. additionTo the residue was added MeCN (25 mL) before it
  4. concentrationwas concentrated under reduced pressure
  5. customthe reaction was partitioned between EtOAc (2×50 mL) and aqueous NaHCO3 (50 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude reaction
  10. customwas purified by RP-HPLC (Table 2, Method j)
  11. additionThe combined product-containing fractions
  12. concentrationwere concentrated under reduced pressure
  13. customto remove MeCN

출처 및 근거

ORD 기록
ord-4b858ae69b6b437a87d3332581493ef4
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365579B2

반응 노트

불러오는 중…