HCID 20745833, compound → HCID 22280082, compound

HRID 1591572Notes

Reaction equation

HRID 1591572 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][O:5][C:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[C:9]([S:16][CH2:17][C:18]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[O:20][N:19]=2)=[CH:8][CH:7]=1.COC(=O)COC1C2CCCCC=2C(S)=CC=1>>[F:32][C:29]([F:30])([F:31])[C:26]1[CH:27]=[CH:28][C:23]([C:21]2[O:20][N:19]=[C:18]([CH2:17][S:16][C:9]3[C:10]4[CH2:11][CH2:12][CH2:13][CH2:14][C:15]=4[C:6]([O:5][CH2:4][C:3]([OH:33])=[O:2])=[CH:7][CH:8]=3)[CH:22]=2)=[CH:24][CH:25]=1

Participants

3

Reactant 2

HCID 20745833HCID 20745833, compoundHCID 20827107HCID 20827107, compound2×

Product 1

HCID 22280082HCID 22280082, compound

Procedure

{4-[5-(4-trifluoromethyl-phenyl)-isoxazol-3-ylmethylsulfanyl]-5,6,7,8-tetrahydro-naphthalen-1-yloxy}-acetic acid methyl ester (compound 102A) The title compound was prepared in the manner analogous to Example 1F using (4-mercapto-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid methyl ester and the product from Example 42C; recrystallization from methanol afforded the title compound. MS m/z 478 (M+1). Step 2. {4-[5-(4-trifluoromethyl-phenyl)-isoxazol-3-ylmethylsulfanyl]-5,6,7,8-tetrahydro-naphthalen-1-yloxy}-acetic acid (compound 102) The title compound was prepared in the manner analogous to Example 1 using the product from Example 102A. mp 167-170° C.; 400 MHz 1H NMR (DMSO-d6) δ 8.01 (d, 2H, J=8 Hz), 7.83 (d, 2H, J=8.3 Hz), 7.14 (d, 2H, J=8.5 Hz), 7.07 (s, 1H), 6.58 (d, 2H, J=8.8 Hz), 4.56 (s, 2H), 4.07 (s, 2H), 2.64 (m, 2H), 2.53 (m, 2H), 1.60 (m, 4H); MS m/z 464 (M+1). The compounds of the present invention can also be prepared using combinatorial chemistry methods. In particular, compounds of Examples 103-134 were prepared using combinatorial chemistry analogous to that previously described in Examples 1-102. The combinatorial chemistry methods useful in the present invention include those where an activated alcohol is contacted with a thiol followed by saponification of the resulting ester to afford the desired products. Such methods can be illustrated by previously described Scheme 1 where compound D is an exemplary thiol, compound Y is an exemplary activated alcohol, and compound F is an exemplary desired product.

Workup

  1. customrecrystallization from methanol

Sources & evidence

ORD record
ord-040f4f9cc9374b8685341a1861d55296
Source dataset
uspto-grants-2007_11
Patent number
USRE039916E1

Reaction notes

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