[6-(3-Methanesulfonyl-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine → 3-(3-{6-[2-(2-Chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxymethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride

HRID 2110667Notes

Reaction equation

HRID 2110667 reaction equation
CS(C1C=C(C2N=[C:15]([O:17]C)N=C(NCCC3C=CC(OC)=CC=3)C=2)C=CC=1)(=O)=O.[Cl:30]C1C=C(Cl)C=CC=1CCNC1N=C(OC)N=C(C2C=C(C=CC=2)OCC#N)C=1.[Cl:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([F:66])[C:61]=1[CH2:67][CH2:68][NH:69][C:70]1[N:75]=[C:74]([O:76][CH3:77])[N:73]=[C:72]([C:78]2[CH:79]=[C:80]([CH:87]=[CH:88][CH:89]=2)[O:81][CH2:82][C:83]([NH:85][OH:86])=[NH:84])[CH:71]=1>>[ClH:30].[Cl:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([F:66])[C:61]=1[CH2:67][CH2:68][NH:69][C:70]1[N:75]=[C:74]([O:76][CH3:77])[N:73]=[C:72]([C:78]2[CH:79]=[C:80]([CH:87]=[CH:88][CH:89]=2)[O:81][CH2:82][C:83]2[NH:84][C:15](=[O:17])[O:86][N:85]=2)[CH:71]=1

Participants

4

Reactant 3

HCID 11582363[6-(3-Methanesulfonyl-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amineHCID 57636062(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-acetonitrileHCID 178494233HCID 178494233, compound

Product 1

HCID 1363883013-(3-{6-[2-(2-Chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxymethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride

Procedure

By proceeding in a similar manner to Example 34(a) above but: (i) substituting (3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-acetonitrile [164 mg, Example 22(f)] for (3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-acetonitrile there is prepared 2-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-N-hydroxy-acetamidine (166 mg, 94%), (ii) substituting 2-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-N-hydroxy-acetamidine for 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl-phenoxy)-N-hydroxy-acetamidine, and (iii) subjecting the product to silica gel chromatography eluting with 0 to 7% MeOH in DCM there is prepared 3-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxymethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride [Example 34(c)] as a solid. LC/MS: RT=2.4 minutes, MS: 472 (M+H). 1H NMR (300 MHz, (CD3)2SO): □12.82 (1H, br s), 7.18-7.55 (7H, m), 6.6 (1H, s), 5.18 (2H, s), 4 (3H, s), 3.68 (2H, m), 3.08 (2H, m). IC50=0.3 nM

Workup

  1. washeluting with 0 to 7% MeOH in DCM
  2. customthere is prepared 3-(3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxymethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride [Example 34(c)] as a solid

Sources & evidence

ORD record
ord-990a63ada38342e39eed184806af9885
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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