Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][C:6]=1[C:7]([N:9]1[CH2:13][CH2:12][CH:11]([O:14]S(C)(=O)=O)[CH2:10]1)=[O:8])([CH3:3])[CH3:2].[CH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][C:28]=1O>>[CH:1]([O:4][C:5]1[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][C:6]=1[C:7]([N:9]1[CH2:13][CH2:12][CH:11]([O:14][C:29]2[CH:28]=[CH:27][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=2)[CH2:10]1)=[O:8])([CH3:3])[CH3:2]
Reactant: Oc1ccc2ccccc2c1
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCC(OS(C)(=O)=O)C1
Product: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCC(Oc2ccc3ccccc3c2)C1
Yield: 40 %

Procedure:
Prepared in analogy to Example 3(c) from rac-methanesulfonic acid 1-(2-isopropoxy-5-methanesulfonyl-benzoyl)-pyrrolidin-3-yl ester (Example 14(a)) and 2-naphthol. The crude material was purified by reversed phase HPLC (acetonitrile/water) to yield the title compound as an amorphous yellow solid (yield 40%). MS (m/e): 454.5 (M+H+, 100%).
Reaction SMILES: C([O:3][C:4]([CH:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH:23]=[CH:22][C:21](=[O:24])[CH2:20][CH2:19]3)=[C:14]([F:25])[CH:13]=2)[CH2:7]1)=O)C.[CH3:26][NH2:27]>CO>[CH3:26][NH:27][C:4]([C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH:23]=[CH:22][C:21](=[O:24])[CH2:20][CH2:19]3)=[C:14]([F:25])[CH:13]=2)[CH2:7]1)=[O:3]
Reactant: CN
Reactant: CCOC(=O)C1CN(c2ccc(N3C=CC(=O)CC3)c(F)c2)C(=O)O1
Solvent: CO
Product: CNC(=O)[C@H]1CN(c2ccc(N3C=CC(=O)CC3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 1 h
Yield: 52.9 %

Procedure:
To a stirred solution of 3-[4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxylic acid ethyl ester (EXAMPLE 69, within Step 6, 120 mg, 0.34 mmol) in MeOH (1 mL) is added MeNH2 (2 mL, 4.0 mmol, 2.0 M solution in MeOH). The reaction mixture is stirred for 1 h at room temperature. Solvent is removed and the residue purified by column chromatography (10% MeOH/CH2Cl2) to give the title compound as a pale yellow solid (60 mg, 52%), 1H NMR (300 MHz, DMSO) δ 8.39 (m, 1H), 7.65–7.38 (m, 4H), 5.06 (dd, 1H), 4.98 (d, 1H), 4.27 (t, 1H), 4.02 (dd, 1H), 3.87 (t, 2H), 2.65 (d, 3H); MS for C16H16FN3O4 m/z 334.5 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.C(N(CC)CC)C>O1CCOCC1>[Cl:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([N:13]2[CH2:14][CH2:15][N:10]([CH3:9])[CH2:11][CH2:12]2)[N:3]=1
Reactant: CN1CCNCC1
Reactant: Clc1cncc(Cl)n1
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CN1CCN(c2cncc(Cl)n2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To 2,6-dichloropyrazine (150 mg, 1.007 mmol) in 1,4-dioxane (1.0 mL) was added 1-methylpiperazine (121.0 mg, 0.13 mL, 1.208 mmol) followed by triethylamine (203.8 mg, 0.281 mL, 2.014 mmol). The reaction mixture was stirred at room temperature for 24 h then concentrated. Purification by flash column chromatography on silica gel using 100:5:1 EtOAc/MeOH/NH4OH (0 to 100%) in EtOAc provided the product. LCMS-ESI+ calc'd for C9H14ClN4 (M+H+): 213.1; Found: 213.2 (M+H+).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:23][CH:22]2[CH:18]([CH2:19][NH:20][CH2:21]2)[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C>C(#N)C.[NH4+].[Cl-]>[Cl:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([N:20]2[CH2:19][CH:18]3[CH2:17][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:23][CH:22]3[CH2:21]2)[N:7]=1
Reactant: CC(C)(C)OC(=O)N1CC2CNCC2C1
Reactant: Clc1ncnc(Cl)n1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CC2CN(c3ncnc(Cl)n3)CC2C1
Yield: 44.1 %

Procedure:
To a solution of 2,4-dichloro-1,3,5-triazine (150 mg, 0.953 mmol) in ACN(5 mL) was added a solution of Intermediate 15 (202 mg, 0.953 mmol) and DIPEA (0.33 mL, 1.91 mmol) in ACN (5 mL) at 0° C. dropwise. After 10 min the mixture was diluted with saturated aqueous NH4Cl solution. The aqueous layer was then extracted with DCM and the combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (Hexanes to 80% EtOAc/Hexanes) afforded the desired product as a white solid (137 mg, 44%). MS (ESI) mass calculated for C14H20ClN5O2, 325.13; m/z found, 326.1.
Reaction SMILES: [CH3:1][NH:2][C:3]1[C:4](=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:5]([N:7]1[CH2:14][CH2:13][CH2:12][C@H:8]1[C:9](O)=[O:10])=[O:6].C[O-].[Na+]>C(O)C>[CH3:1][N:2]1[C:3]2[CH:18]=[CH:17][CH:16]=[CH:15][C:4]=2[C:5](=[O:6])[N:7]2[CH2:14][CH2:13][CH2:12][CH:8]2[C:9]1=[O:10]
Reactant: CNc1ccccc1C(=O)N1CCC[C@H]1C(=O)O
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: CN1C(=O)C2CCCN2C(=O)c2ccccc21

Procedure:
Ten grams of the ethyl ester of 1-(N-methylanthraniloyl)proline is dissolved in 100 ml. of ethanol and 3.0 g. of sodium methylate is added. The reaction mixture is heated at reflux temperature for 8 hours and concentrated to remove the solvent. The residue is shaken with benzene and the benzene solution is washed twice with water and concentrated. The residue is purified by recrystallization from ethyl acetate.
Reaction SMILES: [C:1]([N:5]1[CH:9]=[C:8]([CH:10](O)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)/[C:7](=[N:18]/[C:19](=[O:29])[C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=2[O:27][CH3:28])/[S:6]1)([CH3:4])([CH3:3])[CH3:2].C([SiH](CC)CC)C.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]>>[F:40][C:39]([F:42])([F:41])[C:37]([OH:43])=[O:38].[CH2:10]([C:8]1=[CH:9][N:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[S:6]/[C:7]/1=[N:18]\[C:19](=[O:29])[C:20]1[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=1[O:27][CH3:28])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: COc1ccc(Cl)cc1C(=O)/N=c1\sn(C(C)(C)C)cc1C(O)c1ccccc1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Cl)cc1C(=O)/N=c1\sn(C(C)(C)C)cc1Cc1ccccc1
Temperature: 60 °C
Yield: 25 %

Procedure:
The product from Example 31 (20 mg, 0.05 mmol) in TFA (0.5 mL) was treated with triethylsilane (54 mg, 0.5 mmol). The mixture was heated at 60° C. for 12 hrs, solvent evaporated and the residue purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile: 0.1% aqueous trifluoroacetic acid over 8 minutes (10 minutes run time) at a flow rate of 40 mL/minute to afford 4.8 mg (25%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.61 (s, 9 H) 3.93 (s, 3 H) 4.18 (s, 2 H) 6.92 (d, J=8.90 Hz, 1 H) 7.20-7.28 (m, 1 H) 7.29-7.39 (m, 5 H) 7.78 (s, 1 H) 8.14 (d, J=2.76 Hz, 1 H); MS (DCI/NH4+) m/z 415 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]=1[CH:8]=O.[CH2:10]([O:12][C:13](=[O:26])[C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:16][CH:15]=1)[CH3:11].C(O)C.C([BH3-])#N.[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]=1[CH2:8][N:23]1[CH2:22][CH2:21][N:20]([C:17]2[CH:16]=[CH:15][C:14]([C:13]([O:12][CH2:10][CH3:11])=[O:26])=[CH:19][CH:18]=2)[CH2:25][CH2:24]1
Reactant: O=CC1=C(Br)CCCC1
Reactant: CCOC(=O)c1ccc(N2CCNCC2)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)c1ccc(N2CCN(CC3=C(Br)CCCC3)CC2)cc1

Procedure:
A 100 mL round bottom flask was charged with 2-bromocyclohex-1-enecarbaldehyde, (prepared as described by Arnold, A. et. al. Collect. Czech. Chem. Commun., 1961, 26, 3059-3073.), (42 mmol), 4-piperazin-1-yl-benzoic acid ethyl ester (42 mmol) and ethanol (50 ml). The mixture was stirred and sodium cyanoborohydride (42 mmol) was added. Acetic acid was used to adjust pH to 5-6. The reaction mixture was stirred under N2 at room temperature overnight. The reaction mixture was filtered and washed with ethanol. The filtered solid was discarded and the combined organic layers were concentrated under vacuum. The mixture was purified by silica gel chromatography eluting with 5-10% ethyl acetate in hexanes to provide the title compound.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23](=[O:35])CC3C4C(=CC=CC=4)N(C)C=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C(Cl)(=O)[O:37][CH2:38][C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=1>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23](=[O:35])[O:37][CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2]
Reactant: Cn1cc(CC(=O)N[C@@H]2CCCC[C@H]2N[C@H]2CCCN(c3ccc(C#N)cc3)C2)c2ccccc21
Reactant: COc1ccc(COC(=O)Cl)cc1
Product: COc1ccc(COC(=O)N[C@@H]2CCCC[C@H]2N[C@H]2CCCN(c3ccc(C#N)cc3)C2)cc1

Procedure:
4-Methoxybenzyl (1R,2R)-2-((S)-1-(4-cyanophenyl)piperidin-3-ylamino)cyclohexylcarbamate was synthesized using 4-((S)-3-((1R,2R)-2-aminocyclohexylamino)piperidin-1-yl)benzonitrile (from intermediate D, Example 10) (41 mg, 0.14 mmol) and 4-methoxybenzyl carbonochloridate (45.8 mg, 0.15 mmol) according to General Procedure H to give 28 mg (44%) of light brown solid. Anal. Calcd. for C27H34N4O3 m/z 462.3, found: 463.2 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.52 (d, J=8.7 Hz, 2H), 7.26 (d, J=8.2 Hz, 2H), 7.04 (d, J=8.77 Hz, 1H), 6.96 (d, J=8.9 Hz, 2H), 6.87 (d, J=8.2 Hz, 2H), 4.94 (m, 2H), 3.86 (m, 1H), 3.73 (s, 4H), 3.08 (m, 1H), 2.76 (m, 1H), 2.36 (m, 2H), 1.90 (m, 1H), 1.80 (m, 2H), 1.65 (m, 1H), 1.45 (m, 1H), 1.18 (m, 5H), 1.02 (m, 1H).
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:37]2([CH3:38])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:39])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23]C(OC2C=CC=CC=2)=O)[CH3:22])[CH2:12][C@@H:11]([OH:40])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[CH2:42]/[CH:43]=[CH:44]/[C:45]([CH2:49][CH3:50])([OH:48])[CH2:46][CH3:47].O1CCCC1.[OH-].[K+]>CO>[Si:1]([O:8][C@@H:9]1[C@@:37]2([CH3:38])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:39])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23][CH2:42]/[CH:43]=[CH:44]/[C:45]([CH2:49][CH3:50])([OH:48])[CH2:46][CH3:47])[CH3:22])[CH2:12][C@@H:11]([OH:40])[CH2:10]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: CCC(O)(/C=C/CBr)CC
Reactant: C[C@H](SC(=O)Oc1ccccc1)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCC(O)(/C=C/CS[C@@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)CC
Yield: 84.3 %

Procedure:
Under the same conditions as in Example 3, 1α-(tert-butyldimethylsilyloxy)-3β-hydroxy-20(S)-phenoxycarbonylthiopregna-5,7,16-triene (33.1 mg, 0.0570 mmol), (E)-6-bromo-3-ethyl-4-hexen-3-ol (47.4 mg, 0.229 mmol), tetrahydrofuran (0.5 ml) and 1M KOH solution in methanol (0.5 ml) were reacted and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×1, dichloromethane:ethyl acetate=5:1, developed twice) to give the title compound as a colorless oil (28.2 mg, 84%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:40])([C:33]2[N:34]([CH3:39])[C:35](S)=[N:36][CH:37]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH:13]=[C:12]3[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]#[C:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:22]=2)=[CH:4][CH:3]=1>C(O)C.[Ni]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:40])([C:33]2[N:34]([CH3:39])[CH:35]=[N:36][CH:37]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH:13]=[C:12]3[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]#[C:28][Si:29]([CH3:30])([CH3:31])[CH3:32])[CH:22]=2)=[CH:4][CH:3]=1
Reactant: Cn1c(C(O)(c2ccc(Cl)cc2)c2ccc3c(c2)c(-c2cccc(C#C[Si](C)(C)C)c2)cc(=O)n3C)cnc1S
Agent: [Ni]
Solvent: CCO
Product: Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(C#C[Si](C)(C)C)c1)cc(=O)n2C
Temperature: 25 °C
Yield: 81.7 %

Procedure:
6-[(4-Chloro-phenyl)-hydroxy-(2-mercapto-3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-4-(3-trimethylsilanylethynyl-phenyl)-1H-quinolin-2-one (5.0 g, 8.6 mMol) was dissolved in ethanol (40 mL) to which was added Raney™ nickel (ca. 10 g) and the reaction was heated to reflux. More RANEY™ nickel was added every 20 minutes until mass spectral analysis of the reaction showed that the starting material had been consumed. The reaction mixture was cooled to ambient temperature and filtered through CELITE™ (diatomaceous earth). The CELITE™ was washed with copious amounts of ethanol. The filtrates were combined and concentrated under vacuum to give 3.88 g of the titled compound.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[CH3:6][O:7][C:8]1([O:16][CH3:17])[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=[N:14][OH:15]>C(Cl)Cl>[Cl:4][CH:13]1[CH2:12][CH2:11][CH2:10][C:9](=[N:14][OH:15])[C:8]1([O:7][CH3:6])[O:16][CH3:17]
Reactant: COC1(OC)CCCCC1=NO
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Product: COC1(OC)C(=NO)CCCC1Cl

Procedure:
A solution of 1.66 parts sulfuryl chloride dissolved in 8 parts dry methylene chloride was added under a dry nitrogen atmosphere over a 15-minute period to a stirred solution of 1.73 parts 2,2-dimethoxycyclohexanone oxime dissolved in about 8 parts dry methylene chloride. After the addition was completed, the contents were stirred for an additional hour and then treated by the procedure in Example 1 to yield 1.5 parts of 3-chloro-2,2-dimethoxycyclohexanone oxime.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[CH:13]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[F:25][C:26]([F:31])([F:30])[CH:27]1[O:29][CH2:28]1.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C(#N)C>[N+:1]([C:4]1[CH:5]=[C:6]([N:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:23])([F:24])[CH:20]([F:21])[F:22])[CH:13]=2)[CH2:28][CH:27]([OH:29])[C:26]([F:31])([F:30])[F:25])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: FC(F)(F)C1CO1
Reactant: O=[N+]([O-])c1cccc(NCc2cccc(OC(F)(F)C(F)F)c2)c1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CC#N
Product: O=[N+]([O-])c1cccc(N(Cc2cccc(OC(F)(F)C(F)F)c2)CC(O)C(F)(F)F)c1
Temperature: 55 °C
Yield: 44.8 %

Procedure:
EX-528B) N-(3-nitrophenyl)-3-(1,1,2,2-tetrafluoroethoxy) benzene-methanamine (3.25 g, 9.44 mmol) from EX-528A and 1,1,1-trifluoro-2,3-epoxypropane (0.895 mL, 10.4 mmol) were dissolved in 15 mL of acetonitrile. Ytterbium (III) trifluoromethane-sulfonate (0.77 g, 1.24 mmol) was added, and the stirred solution was warmed to 55° C. for 48 hours. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane 1:10 to give 1.93 g (45%) of the desired 3-[(3-nitrophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a brown oil. HRMS calcd. for C18H16F7N2O4: 457.0998 [M+H]+, found: 457.1008. 1H NMR (CDCl3) 6 3.7 (dd, 1H), 3.9 (dd, 1H), 4.4 (m, 1H), 4.8 (m, 2H), 5.9 (tt, 1H), 7.0-7.2 (m, 4H), 7.3-7.4 (m, 2H), 7.6 (m, 2H).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18]([C:21]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([NH2:46])[CH:43]=[CH:44][CH:45]=2)=[N:8]1.[C:47](Cl)(=[O:52])[CH2:48][CH2:49][CH2:50][CH3:51].C(N(CC)CC)C>O1CCCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18]([C:21]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([NH:46][C:47](=[O:52])[CH2:48][CH2:49][CH2:50][CH3:51])[CH:43]=[CH:44][CH:45]=2)=[N:8]1
Reactant: CCCCC(=O)Cl
Reactant: Nc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCC(=O)Nc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenylamine (0.150 g, 0.248 mmol) in 2.5 mL of tetrahydrofuran was added pentanoyl chloride (0.060 g, 0.496 mmol), followed by triethyl amine (0.173 mL, 1.24 mmol). The reaction was stirred at room temperature for 2 hours. The reaction mixture was then partitioned between ethyl acetate and water. The crude material that was obtained from evaporation of the extracts was not purified further. (Yield not calculated) ES-MS (m/z) 687 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]([C:12]([OH:14])=[O:13])[NH2:11])[CH:6]=[CH:7][C:8]=1[OH:9].Cl.[CH3:16]O>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]([C:12]([O:14][CH3:16])=[O:13])[NH2:11])[CH:6]=[CH:7][C:8]=1[OH:9]
Reactant: CO
Reactant: COc1cc(C(N)C(=O)O)ccc1O
Agent: Cl
Product: COC(=O)C(N)c1ccc(O)c(OC)c1

Procedure:
A cooled suspension of 94 g. (0.476 mole) of 2-(3'-methoxy-4'hydroxyphenyl)glycine in 500 ml. of absolute methanol was gassed at a rapid rate with HCl for 20 minutes. At first a clear solution was obtained and then crystalline product separated in quantity. After 20 hours the methyl ester hydrochloride was filtered and washed sparingly with methanol; 99.6 g. after air drying. A cooled solution of the hydrochloride in 800 ml. of water was adjusted to pH 8 (NaOH) giving a crystalline precipitate of the ester free base; 81.3 g. The IR and NMR spectra were consistent.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH:4]([NH:11][C:12]([O:14][CH3:15])=[O:13])[CH2:5][CH2:6]C(F)(F)F.C(C1C(OC)=NC(CC[O:30][CH2:31][C:32]([F:35])([F:34])[F:33])C(OC)=N1)(C)C>>[CH3:1][O:2][C:3](=[O:16])[CH:4]([NH:11][C:12]([O:14][CH3:15])=[O:13])[CH2:5][CH2:6][O:30][CH2:31][C:32]([F:35])([F:34])[F:33]
Reactant: COC(=O)NC(CCC(F)(F)F)C(=O)OC
Reactant: COC1=NC(C(C)C)C(OC)=NC1CCOCC(F)(F)F
Product: COC(=O)NC(CCOCC(F)(F)F)C(=O)OC

Procedure:
This compound was made by the same procedure as 5,5,5-Trifluoro-2-methoxycarbonylamino-pentanoic acid methyl ester, using 2-Isopropyl-3,6-dimethoxy-5-[2-(2,2,2-trifluoro-ethoxy)-ethyl]-2,5-dihydropyrazine as the starting material. 1H-NMR: 400 MHz, (CDCl3) δ: 5.51-5.43 (br, 1H), 4.51-4.43 (m, 1H), 3.83-3.63 (m, 10H), 2.22-2.13 (m, 1H), 2.13-2.03 (m, 1H) ppm.
Reaction SMILES: [N:1]([C@H:4]([CH2:7][O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:5][OH:6])=[N+:2]=[N-:3].N1C=CC=CC=1.[O:31](S(C(F)(F)F)(=O)=O)[S:32]([C:35]([F:38])([F:37])[F:36])(=O)=[O:33]>C(Cl)Cl>[F:36][C:35]([F:38])([F:37])[S:32]([O:6][CH2:5][C@H:4]([N:1]=[N+:2]=[N-:3])[CH2:7][O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])(=[O:33])=[O:31]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CCCCCCCCCCCCCCCCOC[C@H](CO)N=[N+]=[N-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCCOC[C@H](COS(=O)(=O)C(F)(F)F)N=[N+]=[N-]
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of (S)-2-azido-3-(hexadecyloxy)propan-1-ol (1 eq) and pyridine (4 eq) in DCM (0.1 M) at 0° C., was added Tf2O (2 eq). The reaction was stirred at 0° C. for 1 hour and quenched by H2O. The aqueous phase was extracted with DCM. The combined organic phases were washed with H2O, and the aqueous phase was back extracted with DCM. The combined organic phases were washed with saturated NaHCO3 and brine, dried over anhydrous Na2SO4 and concentrated en vaccuo. The resulting crude was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-10% EtOAc/Hex to give (R)-2-azido-3-(hexadecyloxy)propyl trifluoromethanesulfonate.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([CH2:24][OH:25])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:26]([F:29])([F:28])[F:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:31][C:32](=[O:43])[C:33]#[C:34][C:35]1[CH:40]=[CH:39][C:38](CO)=[CH:37][CH:36]=1>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=1)[CH2:24][O:25][C:38]1[CH:39]=[CH:40][C:35]([C:34]#[C:33][C:32]([OH:43])=[O:31])=[CH:36][CH:37]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:26]([F:29])([F:27])[F:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: COC(=O)C#Cc1ccc(CO)cc1
Product: O=C(O)C#Cc1ccc(OCc2cccc(-c3c(Cc4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc1

Procedure:
The title compound was prepared from [3-(3-benzyl-8-trifluoromethyl-quinolin-4-yl)-phenyl]-methanol and (4-hydroxymethyl-phenyl)-propynoic acid methyl ester according to the procedure of Example 69. MS (ESI) m/z 538.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6].[C:12]1([CH2:18][CH2:19][CH2:20][CH2:21][OH:22])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH3:11][O:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[O:1][C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: COc1ccc(C=O)cc1O
Reactant: OCCCCc1ccccc1
Product: COc1ccc(C=O)cc1OC(=O)CCCc1ccccc1

Procedure:
Following the method of Example 64, the title compound was prepared from 3-hydroxy-4-methoxybenzaldehyde (ALDRICH) and 4-phenyl-1-butanol (Aldrich). M/z calculated for C18H20O3 : 284.1412. Found: 284.1435.
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]3)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(=O)([O-])O.[Na+].CS(C)=O.[Br:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1>O>[Br:27][C:28]1[CH:36]=[CH:35][C:31]([C:32]([N:4]2[CH2:5][CH2:6][N:1]([C:7]3[CH:8]=[C:9]4[C:14](=[CH:15][CH:16]=3)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]4)[CH2:2][CH2:3]2)=[O:33])=[CH:30][CH:29]=1
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: O=C1CCc2cc(N3CCNCC3)ccc2N1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: O=C1CCc2cc(N3CCN(C(=O)c4ccc(Br)cc4)CC3)ccc2N1
Yield: 17.2 %

Procedure:
6-(1-Piperazinyl)-3,4-dihydrocarbostyril (2.6 g) and 1 g of sodium hydrogencarbonate was added to 50 ml of dimethyl sulfoxide and the mixture was stirred with ice cooling while slowly adding dropwise 20 ml of dimethyl sulfoxide solution containing 3.2 g of 4-bromobenzoyl chloride. After completion of addition the reaction mixture was stirred at room temperature for 60 minutes. The reaction mixture was poured into a large amount of water and extracted with chloroform. The extract was washed with saturated sodium hydrogencarbonate solution and subsequently with water and dried over anhydrous sodium sulfate. Chloroform was distilled off and residual crystals were recrystallized from methanol-chloroform to give 0.8 g of 6-[4-(4-bromobenzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril, m.p. 233°-234.5° C., colorless granules.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[O:12][C:13]([C:17]([O:19]CC)=[O:18])=[C:14]([I:16])[N:15]=2)[C:8]([CH3:22])=[CH:7][N:6]=1)(=[O:3])[CH3:2].[Li+].[OH-]>C1COCC1.O>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[O:12][C:13]([C:17]([OH:19])=[O:18])=[C:14]([I:16])[N:15]=2)[C:8]([CH3:22])=[CH:7][N:6]=1)(=[O:3])[CH3:2]
Reactant: CCOC(=O)c1oc(-c2cc(NC(C)=O)ncc2C)nc1I
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)Nc1cc(-c2nc(I)c(C(=O)O)o2)c(C)cn1
Reaction time: 5 h
Yield: 80.7 %

Procedure:
To a solution of ethyl 2-(2-acetamido-5-methylpyridin-4-yl)-4-iodo-1,3-oxazole-5-carboxylate (33.0 g, 80.0 mmol) in THF (660 mL) was added an aqueous solution of LiOH (1M in water, 80 mL). The reaction mixture was allowed to stir for 5 h and then diluted with water. The organic solvent was removed by evaporation and the pH of the remaining aqueous solution was adjusted to 3-4. The mixture was filtered and the solid was collected, washed with water, and dried to give 2-(2-acetamido-5-methylpyridin-4-yl)-4-iodo-1,3-oxazole-5-carboxylic acid (25.0 g, 81%).