1,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → {(S)-6-[(R)-7-Fluoro-4-[2-(1,3,5-trimethyl-pyrazol-4-yl)-pyridin-3-yl]-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid

HRID 237724Notes

Reaction equation

HRID 237724 reaction equation
COC(=O)C[C@H]1C2C=CC(O[C@H]3C4C(=C(C5C(Br)=NC=CC=5)C=CC=4F)CC3)=CC=2OC1.CN1C(C)=C(B2OC(C)(C)C(C)(C)O2)C(C)=N1.BrC1C=CC(F)=C2C=1CC[C@H]2OC1C=CC2[C@H](CC(OC)=O)COC=2C=1.C[O:77][C:78](=[O:114])[CH2:79][C@H:80]1[C:84]2[CH:85]=[CH:86][C:87]([O:89][C@H:90]3[C:98]4[C:93](=[C:94]([C:100]5[C:101]([C:106]6[C:107]([CH3:113])=[N:108][N:109]([CH3:112])[C:110]=6[CH3:111])=[N:102][CH:103]=[CH:104][CH:105]=5)[CH:95]=[CH:96][C:97]=4[F:99])[CH2:92][CH2:91]3)=[CH:88][C:83]=2[O:82][CH2:81]1>>[F:99][C:97]1[CH:96]=[CH:95][C:94]([C:100]2[C:101]([C:106]3[C:107]([CH3:113])=[N:108][N:109]([CH3:112])[C:110]=3[CH3:111])=[N:102][CH:103]=[CH:104][CH:105]=2)=[C:93]2[C:98]=1[C@H:90]([O:89][C:87]1[CH:86]=[CH:85][C:84]3[C@H:80]([CH2:79][C:78]([OH:114])=[O:77])[CH2:81][O:82][C:83]=3[CH:88]=1)[CH2:91][CH2:92]2

Participants

5

Reactant 4

HCID 27953111,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86697103{(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl esterHCID 86697291{(S)-6-[(R)-4-(2-Bromo-pyridin-3-yl)-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl esterHCID 86697394{(S)-6-[(R)-7-fluoro-4-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-3-yl]-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Product 1

HCID 86697393{(S)-6-[(R)-7-Fluoro-4-[2-(1,3,5-trimethyl-pyrazol-4-yl)-pyridin-3-yl]-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid

Procedure

The methyl ester of the title compound is prepared from {(S)-6-[(R)-4-(2-bromo-pyridin-3-yl)-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester and 1,3,5-trimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole following a procedure analogous to that described in Step 5 of Intermediate 1. Saponification of the methyl ester, {(S)-6-[(R)-7-fluoro-4-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-3-yl]-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester, following a procedure analogous to that described for Example 4 gives the title compound; if the title compound does not precipitate from the aqueous solution, the crude title compound is purified by HPLC. LC (method 9): tR=0.88 min; Mass spectrum (ESI+): m/z=514 [M+H]+.

Sources & evidence

ORD record
ord-c7caf96a41a54e4e8ab17c26d4d13d95
Source dataset
uspto-grants-2014_02
Patent number
US08642585B2

Reaction notes

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