(R)-tert-butoxycarbonylamino-{4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-phenyl}-acetic acid → (2S,3S)-N-(2-Fluoro-4-iodo-phenyl)-2-{(R)-4-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-butyramide

HRID 1433764Notes

Reaction equation

HRID 1433764 reaction equation
C(OC(N[C@H](C1C=CC(OCCOC2CCCCO2)=CC=1)C(O)=O)=O)(C)(C)C.C(OC(N[C@H](C1C=CC(OCC(OC)OCC)=CC=1)C(O)=O)=O)(C)(C)C.[O:55]=[C:56]1[NH:60][C@H:59]([C:61]2[CH:66]=[CH:65][C:64]([O:67][CH:68]([CH2:75][O:76][Si](C)(C)C)[CH2:69][O:70][Si](C)(C)C)=[CH:63][CH:62]=2)[C:58](=[O:81])[N:57]1[C@@H:82]([C@H:94]([C:96]1[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=1)[CH3:95])[C:83]([NH:85][C:86]1[CH:91]=[CH:90][C:89]([I:92])=[CH:88][C:87]=1[F:93])=[O:84]>N[C@H](C1C=CC(OC(CO)CO)=CC=1)C(N[C@@H]([C@H](C1C=CC=CC=1)C)C(NC1C=CC(I)=CC=1F)=O)=O>[F:93][C:87]1[CH:88]=[C:89]([I:92])[CH:90]=[CH:91][C:86]=1[NH:85][C:83](=[O:84])[C@@H:82]([N:57]1[C:58](=[O:81])[C@@H:59]([C:61]2[CH:62]=[CH:63][C:64]([O:67][CH:68]([CH2:69][OH:70])[CH2:75][OH:76])=[CH:65][CH:66]=2)[NH:60][C:56]1=[O:55])[C@H:94]([C:96]1[CH:97]=[CH:98][CH:99]=[CH:100][CH:101]=1)[CH3:95]

Participants

5

Reactant 3

HCID 68617730(R)-tert-butoxycarbonylamino-{4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-phenyl}-acetic acid2×HCID 69009549(2S,3S)-2-{(R)-2,5-dioxo-4-[4-(2-trimethylsilanyloxy-1-trimethylsilanyloxymethyl-ethoxy)-phenyl]-imidazolidin-1-yl}-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramideHCID 131727731(R)-tert-butoxycarbonylamino-[4-(methoxy-ethoxy-ethoxy)-phenyl]-acetic acid

Product 1

HCID 57935132(2S,3S)-N-(2-Fluoro-4-iodo-phenyl)-2-{(R)-4-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-butyramide

Reagents, catalysts & solvents 1

HCID 68618945(2S,3S)-2-{(R)-2-amino-2-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-acetylamino}-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramideSolvent

Procedure

Prepared by the same method as described in example 1 except that (i) 2-fluoro-4-iodoaniline was used in place of 4-bromoaniline in step 2, (ii) (R)-tert-butoxycarbonylamino-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-acetic acid (prepared as described in example 160) was used in place of (R)-tert-butoxycarbonylamino-(4-methoxy-phenyl)-acetic acid in step 4, (iii) the diol functionality contained in (2S,3S)-2-{(R)-2-amino-2-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-acetylamino}-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramide was temporarily protected as the bis-trimethylsilyl ether (performed as described in example 114) prior to performing step 6, and (iv) acid catalyzed hydrolysis of (2S,3S)-2-{(R)-2,5-dioxo-4-[4-(2-trimethylsilanyloxy-1-trimethylsilanyloxymethyl-ethoxy)-phenyl]-imidazolidin-1-yl}-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramide was performed as described in example 114 prior to purification and isolation of (2S,3S)—N-(2-fluoro-4-iodo-phenyl)-2-{(R)-4-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-butyramide in step 6.

Workup

  1. customPrepared by the same method
  2. customto purification and isolation of (2S,3S)—N-(2-fluoro-4-iodo-phenyl)-2-{(R)-4-[4-(2-hydroxy-1-hydroxymethyl-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-butyramide in step 6

Sources & evidence

ORD record
ord-f6d837ca738440bb97f0dc19896dc8b5
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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