(2S,3R)-3-(benzyloxy)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)butanoic acid → (S)-N-(4-Cyclopropyl-2-fluoro-phenyl)-3-(4-fluoro-phenyl)-2-{(R)-4-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-propionamide

HRID 1433794노트

반응식

HRID 1433794 반응식
[CH2:1]([O:8][C@H](C)[C@H](NC(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)C(O)=O)C1C=CC=CC=1.N[C@H](C1C=CC(OC[C@H](O)CO)=CC=1)C(N[C@@H]([C@H](C1C=CC=CC=1)C)C(NC1C=CC(I)=CC=1Cl)=O)=O.C(O[C:75](=[O:99])[NH:76][C@H:77]([C:86](=[O:98])[NH:87][C:88]1[CH:93]=[CH:92][C:91]([CH:94]2[CH2:96][CH2:95]2)=[CH:90][C:89]=1[F:97])[CH2:78][C:79]1[CH:84]=[CH:83][C:82]([F:85])=[CH:81][CH:80]=1)(C)(C)C.C(O[C:105]([NH:107][C@H:108]([C:112]1[CH:117]=[CH:116][C:115]([O:118][CH2:119][C@H:120]2COC(C)(C)[O:121]2)=[CH:114][CH:113]=1)C(O)=O)=[O:106])(C)(C)C>NC(C1C=CC(OC(CO)CO)=CC=1)C(N[C@@H](CC1C=CC(F)=CC=1)C(NC1C=CC(C2CC2)=CC=1F)=O)=O>[CH:94]1([C:91]2[CH:92]=[CH:93][C:88]([NH:87][C:86](=[O:98])[C@@H:77]([N:76]3[C:75](=[O:99])[C@@H:108]([C:112]4[CH:113]=[CH:114][C:115]([O:118][CH:119]([CH2:120][OH:121])[CH2:1][OH:8])=[CH:116][CH:117]=4)[NH:107][C:105]3=[O:106])[CH2:78][C:79]3[CH:84]=[CH:83][C:82]([F:85])=[CH:81][CH:80]=3)=[C:89]([F:97])[CH:90]=2)[CH2:96][CH2:95]1

참가 물질

6

반응물 4

HCID 16213170(2S,3R)-3-(benzyloxy)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)butanoic acidHCID 67001404(R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acidHCID 68619453(S)-[1-(4-cyclopropyl-2-fluoro-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl esterHCID 69006543(2S,3S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide

생성물 1

HCID 17757740(S)-N-(4-Cyclopropyl-2-fluoro-phenyl)-3-(4-fluoro-phenyl)-2-{(R)-4-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-propionamide

시약·촉매·용매 1

HCID 68620559(S)-2-{2-amino-2-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-acetylamino}-N-(4-cyclopropyl-2-fluoro-phenyl)-3-(4-fluoro-phenyl)-propionamide용매

실험 절차

Prepared by the same method as described in example 3 except that (i) (S)-2-tert-butoxycarbonylamino-3-(4-fluoro-phenyl)-propionic acid was used in place of (2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyric acid in step 1, (ii) (S)-[1-(2-fluoro-4-iodo-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester was converted in to (S)-[1-(4-cyclopropyl-2-fluoro-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester after step 2 and prior to step 3 (using the conditions described below), (iii) (R)-tert-butoxycarbonylamino-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-acetic acid (prepared as described below) was used in place of (R)-tert-butoxycarbonylamino-{4-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-acetic acid in step 4, and (iv) the diol functionality contained in (S)-2-{2-amino-2-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-acetylamino}-N-(4-cyclopropyl-2-fluoro-phenyl)-3-(4-fluoro-phenyl)-propionamide was temporarily protected as the bis-trimethylsilyl ether during step 6 by the same method as described in example 114.

후처리

  1. customPrepared by the same method

출처 및 근거

ORD 기록
ord-2ae8f6a8246b46e6ad6ffb1f93afe452
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612212B2

반응 노트

불러오는 중…