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Sodium Carbonate → HCID 72548394, 화합물

HRID 2206433
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HRID 2206433 반응식
[Cl:1][C:2]1[C:3]([F:46])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:43]=[CH:42][C:34]([C:35]([O:37][CH2:38][C:39](O)=[O:40])=[O:36])=[CH:33][C:32]=2[O:44][CH3:45])=[O:29])[CH:5]=[CH:6][CH:7]=1.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.Cl.[NH2:81][C@@H:82]([CH2:93][CH2:94][C:95]([O:97][CH2:98][C:99]1[CH:104]=[CH:103][CH:102]=[CH:101][CH:100]=1)=[O:96])[C:83]([O:85][CH2:86][C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1)=[O:84].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[CH2:86]([O:85][C:83](=[O:84])[C@@H:82]([NH:81][C:39](=[O:40])[CH2:38][O:37][C:35](=[O:36])[C:34]1[CH:42]=[CH:43][C:31]([NH:30][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:46])[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10]2)=[O:29])=[C:32]([O:44][CH3:45])[CH:33]=1)[CH2:93][CH2:94][C:95]([O:97][CH2:98][C:99]1[CH:104]=[CH:103][CH:102]=[CH:101][CH:100]=1)=[O:96])[C:87]1[CH:88]=[CH:89][CH:90]=[CH:91][CH:92]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 5

HCID 10340Sodium CarbonateHCID 81531Diisopropylethylamine2회HCID 199613(S)-Dibenzyl 2-aminopentanedioate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 72548393HCID 72548393, 화합물

생성물 1

HCID 72548394
HCID 72548394, 화합물
수율 33%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

In a 20 mL round-bottomed flask, 2-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)-acetic acid (Example 69, 133 mg, 197 μmol), HATU (75.0 mg, 197 μmol) and Hunig's base (51.0 mg, 68.9 μL, 394 μmol) were combined with dry tetrahydrofuran (1 mL) to give an off-white suspension at room temperature. The mixture was stirred for 30 min and a solution of (S)-dibenzyl 2-aminopentanedioate hydrochloride (108 mg, 296 μmol) and Hunig's base (2 eq.) in dry tetrahydrofuran (1 mL) was added. After 1 h, the reaction mix was directly purified with reverse phase high-performance liquid chromatography to isolate the desired fraction, which was neutralized with saturated aqueous sodium carbonate solution, extracted with methylene chloride. The methylene chloride layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give (S)-2-[2-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-acetylamino]-pentanedioic acid dibenzyl ester (63 mg, 33% yield). LCMS (ES+) m/z calcd. for C52H51Cl2F2N4O9 [(M+H)+]: 983. found: 983.

후처리

  1. customto give an off-white suspension at room temperature
  2. waitAfter 1 h
  3. additionthe reaction mix
  4. customwas directly purified with reverse phase high-performance liquid chromatography
  5. customto isolate the desired fraction, which
  6. extractionextracted with methylene chloride
  7. washThe methylene chloride layer was washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-ec2f52d8374a4990be11fa1b8f11e8ca
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09371280B2

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