Trifluoroacetic acid → N-(2-Fluoro-4-iodo-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-(2-trifluoromethyl-phenyl)-propionamide

HRID 1433756Notes

Reaction equation

HRID 1433756 reaction equation
C(O[C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20]COC2CCCCO2)=[CH:15][CH:14]=1)[C:10]([OH:12])=O)=[O:7])(C)(C)C.C(OC(N[C@H:37]([C:41]1[CH:46]=[CH:45][C:44](OC[C@H]2COC(C)(C)O2)=[CH:43][CH:42]=1)[C:38](O)=O)=O)(C)(C)C.C(OC([NH:63][C@H](C1C=CC(OCC(OC)OCC)=CC=1)C(O)=O)=O)(C)(C)C.[F:82][C:83]([F:88])([F:87])C(O)=O.N[C@@H](CC1C=CC=CC=1C(F)(F)F)[C:91]([NH:93][C:94]1[CH:99]=[CH:98][C:97]([I:100])=[CH:96][C:95]=1[F:101])=[O:92].C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>>[F:101][C:95]1[CH:96]=[C:97]([I:100])[CH:98]=[CH:99][C:94]=1[NH:93][C:91](=[O:92])[CH:38]([N:63]1[C:10](=[O:12])[C@@H:9]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[NH:8][C:6]1=[O:7])[CH2:37][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][C:46]=1[C:83]([F:82])([F:87])[F:88]

Participants

9

Reactant 8

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 130500O-benzotriazol-1-yl-tetramethyluroniumHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67001404(R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acidHCID 68617730(R)-tert-butoxycarbonylamino-{4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-phenyl}-acetic acidHCID 68620547(S)-2-amino-N-(2-fluoro-4-iodo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionamideHCID 131727731(R)-tert-butoxycarbonylamino-[4-(methoxy-ethoxy-ethoxy)-phenyl]-acetic acid

Product 1

HCID 68619771N-(2-Fluoro-4-iodo-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-(2-trifluoromethyl-phenyl)-propionamide

Procedure

Prepared by the same method as described in example 4 except that (i) (S)-2-tert-butoxycarbonylamino-3-(2-trifluoromethyl-phenyl)-propionic acid was used in place of (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid in step 1, (ii) 2-fluoro-4-iodoaniline was used in place of 4-iodoaniline in step 2, (iii) the trifluoroacetic acid salt of (S)-2-amino-N-(2-fluoro-4-iodo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionamide was isolated in step 3 and used directly in step 4 with 1.0 equivalent of triethylamine and (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride as the coupling reagent in place of O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexaflurorophosphate, and (iv) after performing step 5, the diastereomers (resulting from racemization in step 2) of 2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-N-(2-fluoro-4-iodo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionamide were separated by chromatography over silica gel gradient eluted between 40 and 60% v/v ethyl acetate in hexane. The slower moving component was collected and after concentration in vacuo carried on to step 6.

Workup

  1. customPrepared by the same method
  2. customwas isolated in step 3
  3. customthe diastereomers (resulting from racemization in step 2) of 2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-N-(2-fluoro-4-iodo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionamide were separated by chromatography over silica gel gradient
  4. washeluted between 40 and 60% v/v ethyl acetate in hexane
  5. customwas collected
  6. concentrationafter concentration in vacuo

Sources & evidence

ORD record
ord-9108ec0a6c9144df88d56f161804bf72
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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