1,2-Dichloroethane → HCID 90331702, 화합물

HRID 1752942

반응식

HRID 1752942 반응식
[NH2:1][C@H:2]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=2[F:23])=[CH:12][CH:11]=1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[P:24]([CH2:28][CH2:29][C:30](O)=[O:31])([OH:27])([OH:26])=[O:25].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:22][C:20]1[CH:19]=[CH:18][C:17]([F:23])=[C:16]([C:13]2[CH:14]=[CH:15][C:10]([CH2:9][C@@H:2]([NH:1][C:30](=[O:31])[CH2:29][CH2:28][P:24](=[O:25])([OH:27])[OH:26])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:11][CH:12]=2)[CH:21]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 16823-Phosphonopropionic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59607661HCID 59607661, 화합물

생성물 1

HCID 90331702HCID 90331702, 화합물수율 11.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(R)-ethyl 3-amino-4-(5′-chloro-2′-fluoro-[1,1-biphenyl]-4-yl)butanoate (114 mg, 0.306 mmol), 3-phosphonoproprionic acid (47.2 mg, 0.306 mmol), EDC (58.7 mg, 0.306 mmol) and HOBT (46.9 mg, 0.306 mmol) were mostly dissolved in DMF (1 mL), and DIPEA (0.321 mL, 1.837 mmol) was added. The reaction mixture was stirred and heated at 70° C. approximately 18 hours, then filtered and purified by HPLC: 30-80% ACN/H2O 0.1% TFA, 40 mL/min over 15 min 30×100 Sunfire C18, product elutes approximately 5.5-8 min. A mixed fraction was repurified on a 20-55% gradient over 20 min, and product eluted ˜12.5-13 min. The fractions were evaporated to dryness to afford (R)-(3-((1-(5′-chloro-2′-fluoro-[1,1-biphenyl]-4-yl)-4-ethoxy-4-oxobutan-2-yl)amino)-3-oxopropyl)phosphonic acid (17 mg) LCMS (ES+) C21H24ClFNO6P: Calc.: 471.1; Found: 472.0[M+H]+.

후처리

  1. temperatureheated at 70° C. approximately 18 hours
  2. filtrationfiltered
  3. custompurified by HPLC
  4. customA mixed fraction was repurified on a 20-55% gradient over 20 min
  5. washproduct eluted ˜12.5-13 min
  6. customThe fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-0bb2365961004c3b8ad64fa1862f09ee
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163040B2

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