Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[C:9]([CH2:12][O:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[CH:16]=[C:17]([C:23](O)=[O:24])[NH:18]4)=[CH:10][O:11][C:7]=2[CH:6]=[C:5]([O:26][CH3:27])[CH:4]=1.Cl.Cl.Cl.[NH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH2:38][C@@H:39]([N:41]2[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]2)[CH3:40])[CH2:34][CH2:33]1>>[OH:47][CH:44]1[CH2:43][CH2:42][N:41]([C@@H:39]([CH3:40])[CH2:38][N:35]2[CH2:34][CH2:33][CH:32]([NH:31][C:23]([C:17]3[NH:18][C:19]4[C:15]([CH:16]=3)=[C:14]([O:13][CH2:12][C:9]3[C:8]5[C:3]([O:2][CH3:1])=[CH:4][C:5]([O:26][CH3:27])=[CH:6][C:7]=5[O:11][CH:10]=3)[CH:22]=[CH:21][CH:20]=4)=[O:24])[CH2:37][CH2:36]2)[CH2:46][CH2:45]1
Reactant: C[C@@H](CN1CCC(N)CC1)N1CCC(O)CC1
Reactant: COc1cc(OC)c2c(COc3cccc4[nH]c(C(=O)O)cc34)coc2c1
Agent: Cl
Product: COc1cc(OC)c2c(COc3cccc4[nH]c(C(=O)NC5CCN(C[C@H](C)N6CCC(O)CC6)CC5)cc34)coc2c1

Procedure:
This compound is synthesized analogously to example 1 from 4-(4,6-dimethoxy-benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid, 126 (see example 99) and amine 50.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([NH2:7])=[N:4][CH:3]=1.[Cl:8][C:9]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:10]=1[C:11](O)=[O:12].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O1CCCC1>[Cl:8][C:9]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:10]=1[C:11]([NH:7][C:5]1[S:6][C:2]([CH3:1])=[CH:3][N:4]=1)=[O:12]
Reactant: Cc1cnc(N)s1
Reactant: O=C(O)c1cc(Cl)ccc1Cl
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cc1cnc(NC(=O)c2cc(Cl)ccc2Cl)s1
Temperature: 22 °C
Reaction time: 14 h
Yield: 79.1 %

Procedure:
To a solution of 5-methylthiazole-2-amine (Aldrich, 1.0 g, 8.76 mmol) in tetrahydrofuran (10 mL) was added 2,5-dichlorobenzoic acid (Aldrich) (2.01 g, 10.51 mmol), triethylamine (2.93 mL, 21.02 mmol), and 1-propanephosphonic acid cyclic anhydride (Aldrich, 50% solution in ethyl acetate, 6.19 mL, 10.51 mmol). The reaction mixture was stirred at 22° C. for 14 h., cooled, and quenched with saturated aqueous NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (2×40 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 1.99 g of the title compound. MS (ESI+) m/z 287 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].Cl.Cl[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:14][C:15]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=2)=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: ClCc1ccc2ccccc2n1
Reactant: O=[N+]([O-])c1cc(O)ccc1Cl
Agent: Cl
Product: O=[N+]([O-])c1cc(OCc2ccc3ccccc3n2)ccc1Cl

Procedure:
A solution of 4-chloro-3-nitro-phenol was reacted with 2-Chloromethyl-quinoline hydrochloride salt using the conditions described in Example 10C to provide 2-(4-Chloro-3-nitro-phenoxymethyl)-quinoline which was treated sequentially using the procedures from Examples 10D and 10E to provide the title product.
Reaction SMILES: [Cl-].[Ca+2].[Cl-].[BH4-].[Na+].[Cl:6][C:7]1[N:12]=[C:11]([C:13](OC)=[O:14])[CH:10]=[CH:9][C:8]=1[C:17]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:18]=1[F:25].Cl.C(=O)([O-])O.[Na+]>C(O)C.C1COCC1>[Cl:6][C:7]1[N:12]=[C:11]([CH2:13][OH:14])[CH:10]=[CH:9][C:8]=1[C:17]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:18]=1[F:25]
Reactant: COC(=O)c1ccc(-c2cc(OC)ccc2F)c(Cl)n1
Agent: Cl
Agent: O=C([O-])O
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: CCO
Product: COc1ccc(F)c(-c2ccc(CO)nc2Cl)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 97.2 %

Procedure:
Under a nitrogen atmosphere, to a suspension of calcium chloride (12.3 g) in ethanol (100 mL) and THF (50 mL) was added sodium tetrahydroborate (2.62 g) at 0° C., and the mixture was stirred at 0° C. for 10 min. A solution of methyl 6-chloro-5-(2-fluoro-5-methoxyphenyl)picolinate (8.30 g) in ethanol (25 mL) and THF (50 mL) was added at room temperature and the mixture was stirred for 14 hr. 1N Hydrochloric acid was added to the reaction mixture, and the mixture was neutralized with aqueous sodium hydrogen carbonate solution. The reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (7.30 g) as a pale-gray amorphous solid.
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:11][C:12]=2[CH2:14]O)[CH:7]=[N:6]1)[CH:2]([CH3:4])[CH3:3].[CH3:21][O:22][C:23]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][N:29]=[CH:28]2)=[O:24]>>[CH3:21][O:22][C:23]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:7][C:8]1[CH:9]=[C:10]([O:16][C:17]([F:18])([F:20])[F:19])[CH:11]=[C:12]3[C:13]=1[N:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[N:6]=[CH:14]3)[N:29]=[CH:28]2)=[O:24]
Reactant: CC(C)Cn1ncc2cc(OC(F)(F)F)cc(CO)c21
Reactant: COC(=O)c1ccc2[nH]ncc2c1
Product: COC(=O)c1ccc2c(cnn2Cc2cc(OC(F)(F)F)cc3cnn(CC(C)C)c23)c1
Yield: 46 %

Procedure:
Compound 29 was prepared following general method 3A, using compound 21 as a starting material and 1H-indazole-5-carboxylic acid methyl ester as the heterocycle. Yield: 46%.
Reaction SMILES: Br[C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+].[NH:57]1[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:8][C:3]1[C:2]([N:57]2[CH2:62][CH2:61][O:60][CH2:59][CH2:58]2)=[CH:7][CH:6]=[CH:5][N:4]=1
Reactant: C1COCCN1
Reactant: Clc1ncccc1Br
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: Cc1ccccc1
Product: Clc1ncccc1N1CCOCC1
Temperature: 100 °C
Reaction time: 0.08 h

Procedure:
To a glass microwave vial was added 3-bromo-2-chloropyridine (0.5489 g, 2.85 mmol), Pd2(dba)3 (0.131 g, 0.143 mmol), xantphos (0.165 g, 0.285 mmol), and sodium tert-butoxide (0.524 mL, 4.28 mmol). The vial was capped and placed under vacuum for 5 minutes. Morpholine (0.248 mL, 2.85 mmol) and toluene (2 mL) were added. The reaction was allowed to stir at 100° C. Upon completion, the reaction was allowed to cool to room temperature. Solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (25M), eluting with a gradient of 10% to 80% EtOAc in hexane, to provide 4-(2-chloropyridin-3-yl)morpholine. MS: [M+H]=199.0.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([O:16][CH3:17])=[N:14][CH:15]=2)[N:7]([CH:20]([CH3:22])[CH3:21])[C:6]=1[CH:23]([C:25]1[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([F:33])[CH:26]=1)O)=[O:4].[NH2:34][C:35]1[CH:36]=[C:37]([Cl:43])[C:38](=[O:42])[N:39]([CH3:41])[CH:40]=1.C(OC(C1C=CN(C(C)C)C=1C(C1C=CC(C#N)=CC=1)O)=O)C.ClC1C=C(C=CC=1F)N>>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([O:16][CH3:17])=[N:14][CH:15]=2)[N:7]([CH:20]([CH3:22])[CH3:21])[C:6]=1[CH:23]([NH:34][C:35]1[CH:36]=[C:37]([Cl:43])[C:38](=[O:42])[N:39]([CH3:41])[CH:40]=1)[C:25]1[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([F:33])[CH:26]=1)=[O:4]
Reactant: Cn1cc(N)cc(Cl)c1=O
Reactant: COC(=O)c1cc(-c2cnc(OC)nc2OC)n(C(C)C)c1C(O)c1ccc(C#N)c(F)c1
Agent: CCOC(=O)c1ccn(C(C)C)c1C(O)c1ccc(C#N)cc1
Agent: Nc1ccc(F)c(Cl)c1
Product: COC(=O)c1cc(-c2cnc(OC)nc2OC)n(C(C)C)c1C(Nc1cc(Cl)c(=O)n(C)c1)c1ccc(C#N)c(F)c1

Procedure:
The title compound was prepared in analogy to the procedures described for Step H2 and Step H3 but 2-[(4-cyano-3-fluoro-phenyl)-hydroxy-methyl]-5-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester (Step 195.2) and 5-amino-3-chloro-1-methyl-1H-pyridin-2-one (Step E5) were used instead of 2-[(4-cyano-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester and 3-chloro-4-fluoroaniline respectively. The title compound was obtained as a blue solid. tR: 1.10 min (HPLC 3); ESI-MS: tR=1.07 min, [M+H]+ 595/597 (LC-MS 1); TLC: Rf=0.29 (EtOAc).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[N:11]3[N:17]=[CH:18][C:19]([C:20]([OH:22])=O)=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.O[NH:24][C:25](=[NH:36])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([S:32](=[O:35])(=[O:34])[NH2:33])[CH:27]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[N:11]3[N:17]=[CH:18][C:19]([C:20]4[O:22][N:36]=[C:25]([C:26]5[CH:27]=[C:28]([S:32]([NH2:33])(=[O:34])=[O:35])[CH:29]=[CH:30][CH:31]=5)[N:24]=4)=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: O=C(O)c1cnn2c(C3CC3)cc(-c3ccc(Cl)cc3)nc12
Reactant: N=C(NO)c1cccc(S(N)(=O)=O)c1
Product: NS(=O)(=O)c1cccc(-c2noc(-c3cnn4c(C5CC5)cc(-c5ccc(Cl)cc5)nc34)n2)c1

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.28) (157 mg, 0.5 mmol) and N-hydroxy-3-sulfamoyl-benzamidine [CAS-No. 9000-88-7] (161 mg, 0.75 mmol) according to general procedure II. Obtained after purification by column chromatography (dichloromethane/MeOH/NH4OH) and crystallization (dichloromethane) as an off-white solid (113 mg, 46%). MS (EI) 492.1 [(M)+]; mp 285° C.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.Br[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[S:27][C:26]([N:28]([CH3:39])[CH:29]3[CH2:34][C:33]([CH3:36])([CH3:35])[NH:32][C:31]([CH3:38])([CH3:37])[CH2:30]3)=[N:25][N:24]=2)=[C:19]([Cl:40])[CH:18]=1.C([O-])([O-])=O.[Na+].[Na+].CO>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CS(C)=O>[Cl:40][C:19]1[CH:18]=[C:17]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)[CH:22]=[CH:21][C:20]=1[C:23]1[S:27][C:26]([N:28]([CH3:39])[CH:29]2[CH2:34][C:33]([CH3:35])([CH3:36])[NH:32][C:31]([CH3:38])([CH3:37])[CH2:30]2)=[N:25][N:24]=1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: CN(c1nnc(-c2ccc(Br)cc2Cl)s1)C1CC(C)(C)NC(C)(C)C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CS(C)=O
Solvent: CO
Product: CN(c1nnc(-c2ccc(-c3cnn(C)c3)cc2Cl)s1)C1CC(C)(C)NC(C)(C)C1
Temperature: 80 °C
Yield: 55.1 %

Procedure:
To a stirred solution of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (129 mg, 0.620 mmol) and 5-(4-bromo-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (250 mg, 0.563 mmol) in dioxane (4 mL) was added Pd(PPh3)4 (33 mg, 0.028 mmol), followed by a solution of Na2CO3 (179 mg, 1.69 mmol) in water (1 mL). The reaction mixture was purged with nitrogen, sealed, and heated at 80° C. for an hour under microwave irradiation. The reaction mixture was diluted with EtOAc (50 mL) and washed with saturated NaHCO3(aq) (25 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to afford the crude product as a brown solid. The crude material was taken up in a 2:1 mixture of MeOH:DMSO (4.5 mL), passed through a syringe filter, and purified by UV-directed preparative HPLC under basic conditions (5 mM NH4OH), collecting at 335 nm to afford the title compound as a white solid (138 mg, 55% yield). LC-MS: Rt 0.90 min; MS m/z 445.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.32 (s, 1H), 8.02 (s, 1H), 7.99 (d, J=8.08 Hz, 1H), 7.84 (d, J=1.52 Hz, 1H), 7.67 (dd, J=8.08, 1.52 Hz, 1H), 4.36 (tt, J=12.44, 3.47 Hz, 1H), 3.88 (s, 3H), 3.01 (s, 3H), 1.62 (dd, J=11.87, 3.28 Hz, 2H), 1.43 (t, J=12.13 Hz, 2H), 1.28 (br. s., 1H), 1.21 (s, 6H), 1.09 (s, 6H). LC-MS: Rt 1.84 mins; MS m/z 444.8 M+ [Method B].
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][N:11]=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C:13](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][N:11]([CH3:13])[NH:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: Brc1ccc(-c2nnn[nH]2)cc1
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: O
Product: CN1NN=C(c2ccc(Br)cc2)N1

Procedure:
4-Bromophenyltetrazole (225 mg; 1.0 mmol) and potassium carbonate (140 mg; 1.0 mmol) are dissolved in dimethylformamide (3 mL), and a solution of methyliodide (140 mg; 1.0 mmol) in dimethylformamide (1 mL) is added dropwise under stirring. After 2 hours reaction time at room temperature methyliodide (28 mg; 0.2 mmol) is added and the mixture is stirred further for 90 minutes. The reaction is then diluted with water (4 mL), the precipitated white solid is filtered off and is rinsed once with water. After drying under high vacuum the desired product is obtained as a 95:5 mixture of regioisomers (188 mg; 0.79 mmol).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:32][CH3:33])=[C:7]([S:9]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[S:27]([CH3:30])(=[O:29])=[O:28])=[CH:17][C:16]=2[OH:31])(=[O:11])=[O:10])[CH:8]=1)#[N:2].C(N(CC)C(C)C)(C)C.Br[CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46].O>CN(C)C=O>[CH2:48]([O:47][C:45](=[O:46])[CH2:44][O:31][C:16]1[CH:17]=[C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[S:27]([CH3:30])(=[O:28])=[O:29])[CH:19]=[CH:20][C:15]=1[CH2:14][CH2:13][NH:12][S:9]([C:7]1[CH:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=1[O:32][CH3:33])(=[O:10])=[O:11])[CH3:49]
Reactant: CCOC(=O)CBr
Reactant: COc1ccc(C#N)cc1S(=O)(=O)NCCc1ccc(-c2ccccc2S(C)(=O)=O)cc1O
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)COc1cc(-c2ccccc2S(C)(=O)=O)ccc1CCNS(=O)(=O)c1cc(C#N)ccc1OC
Temperature: 50 °C
Reaction time: 15 h

Procedure:
To a solution of 5.72 g of 5-cyano-N-[2-(3-hydroxy-2′-methanesulfonylbiphenyl-4-yl)ethyl]-2-methoxybenzenesulfonamide in 57 mL of N,N-dimethylformamide were added 2.46 mL of N,N-diisopropylethylamine and 1.37 mL of ethyl bromoacetate. After being stirred at 50° C. for 15 hours, and the reaction mixture was poured into 100 mL of water, and extracted with a mixture of 150 mL of ethyl acetate and 20 mL of toluene. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: ethyl acetate-hexane) to give 2.96 g of ethyl[4-[2-(5-cyano-2-methoxybenzenesulfonylamino)ethyl]-2′-methanesulfonylbiphenyl-3-yloxy]acetate as an amorphous material.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[F:13][C:14]([F:27])([F:26])[O:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>>[F:27][C:14]([F:13])([F:26])[O:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:1][C:2]2[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=2)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: CCOC(=O)Cc1csc(N)n1
Reactant: O=S(=O)(Cl)c1ccc(OC(F)(F)F)cc1
Product: CCOC(=O)Cc1csc(NS(=O)(=O)c2ccc(OC(F)(F)F)cc2)n1

Procedure:
The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 4-(trifluoromethoxy)benzenesulfonyl chloride as described in the synthetic METHOD B to give a white solid (29.1 mg) with purity >90%. MS (pos) m/z 411.1.
Reaction SMILES: CCCC[Sn]([O:14][Sn:15]([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:16][CH2:17][CH2:18][CH3:19])(CCCC)CCCC.[CH2:28]([N:32]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:33][CH2:34]O)[CH2:29][CH2:30][CH3:31].O>C1C=CC=CC=1>[CH2:24]([Sn:15]([O:14][CH2:34][CH2:33][N:32]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:28][CH2:29][CH2:30][CH3:31])([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:25][CH2:26][CH3:27]
Reactant: CCCCN(CCO)CCCC
Reactant: CCCC[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)CCCC
Solvent: O
Solvent: c1ccccc1
Product: CCCCN(CCCC)CCO[Sn](CCCC)(CCCC)CCCC

Procedure:
N,N-Dibutylaminoethyl Tributylstannyl Ether is prepared from 59.6 gm (0.1 mole) bis(tributyltin) oxide and 34.6 gm (0.2 mole) N,N-dibutylethanolamine in 200 ml benzene. This is stirred and heated to reflux in a system that contains a Dean-Starke tube. After 30 minutes water began to collect in the Dean-Starke tube and after refluxing for a period of 22 hours a total of 1.8 ml of water (theory 1.8 ml) had collected. A rotating evaporator is used to remove the benzene and to provide 95.1 gm of red-orange liquid. This is fractionated at reduced pressure with collection at 163°-166° C. at 0.7 mm of 73.1 gm of yellow liquid (Percent yield - 79). Infrared spectral analysis shows this to be the desired ether.
Reaction SMILES: [NH2:1][CH:2]([C:5]([O:7][CH3:8])=[O:6])[CH2:3][OH:4].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>C(Cl)Cl.C(N(CC)CC)C>[OH:4][CH2:3][CH:2]([NH:1][S:17]([C:14]1[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[CH:16][CH:15]=1)(=[O:19])=[O:18])[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)C(N)CO
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C(CO)NS(=O)(=O)c1ccc(OC)cc1
Temperature: 0 °C
Reaction time: 48 h
Yield: 53.8 %

Procedure:
To a mixture of D,L-serine, methyl ester (5.0 g, 32.14 mmol) and triethylamine (15.7 ml, 0.012 mmol) in methylene chloride (100 ml), cooled to 0° C., was added, in portions, 4-methoxybenzenesulfonyl chloride (6.64 g, 32.14 mmol). The mixture was then stirred under argon at room temperature for 48 hours. The reaction was diluted with methylene chloride (100 ml), washed with water (60 ml), 2N citric acid (60 ml), saturated sodium chloride (60 ml), and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give a solid. Crystallization from ethyl acetate gave 5.0 g (54%) of the product as white crystals, mp 92-94° C.
Reaction SMILES: [CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[Li]CCCC.[F:12][CH2:13][C:14](OCC)=[O:15].B(F)(F)F.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[F:12][CH2:13][C:14](=[O:15])[C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1]
Reactant: CCOC(=O)CF
Reactant: C#C[Si](C)(C)C
Agent: FB(F)F
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C[Si](C)(C)C#CC(=O)CF
Reaction time: 0.67 h
Yield: 85.2 %

Procedure:
49.1 g (499 mmol) of trimethylsilyl acetylene was dissolved in 250 mL of anhydrous tetrahydrofuran, and the inner temperature was lowered to about −55° C., and then 210 mL (525 mmol) of 2.5 M n-BuLi in n-hexane was added thereto over about 25 minutes with maintaining the inner temperature below −30° C. After stirring for about 40 minutes, 52.9 g (499 mmol) of ethyl fluoroacetate was added to the reaction mixture over 5 minutes with maintaining the inner temperature below −25° C., and then 74.4 g (524 mmol) of BF3.OEt was added thereto over 15 minutes with maintaining the inner temperature −55° C. to −65° C. After finishing the addition, the reaction mixture was stirred at 20° C. for 2 hours, and 250 mL of 10% ammonium chloride aqueous solution was added thereto to finish the reaction. The organic layer was separated, and the aqueous layer was extracted with 200 mL of ethylacetate. The combined organic phase was washed with 250 mL of brine, and concentrated under reduced pressure. The residue was distilled under vacuum at 10 mbar and 68° C. to give the compound of formula (9) (67.3 g, 85%) as clear oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C@@H:4]([O:15][CH2:16][CH3:17])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[CH2:13][CH3:14].Cl[CH2:20][C:21]1[N:22]=[C:23]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[O:24][C:25]=1[CH3:26].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>>[CH3:1][O:2][C:3](=[O:18])[C@@H:4]([O:15][CH2:16][CH3:17])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:20][C:21]2[N:22]=[C:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH3:33])[O:24][C:25]=2[CH3:26])=[CH:8][C:7]=1[CH2:13][CH3:14]
Reactant: CCO[C@@H](Cc1ccc(O)cc1CC)C(=O)OC
Reactant: Cc1ccccc1-c1nc(CCl)c(C)o1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Product: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3C)oc2C)cc1CC)C(=O)OC

Procedure:
In analogy to the procedure described in example 1 f], (2S)-2-ethoxy-3-(2-ethyl-4-hydroxy-phenyl)-propionic acid methyl ester (example 8 g]) was reacted with 4-chloromethyl-5-methyl-2-o-tolyl-oxazole (example 1 e]) in the presence of cesium carbonate and potassium iodide to yield (S)-2-ethoxy-3-[2-ethyl-4-(5-methyl-2-o-tolyl-oxazol-4-ylmethoxy)-phenyl]-propionic acid methyl ester as colorless liquid.
Reaction SMILES: F[C:2]1([O:9][C:10]#[C:11][CH3:12])[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][CH2:3]1.[F:13]C1C=C(O)C=C(F)C=1>>[F:8][C:6]1[CH:7]=[C:2]([O:9][CH2:10][C:11]#[CH:12])[CH:3]=[C:4]([F:13])[CH:5]=1
Reactant: Oc1cc(F)cc(F)c1
Reactant: CC#COC1(F)C=C(F)C=CC1
Product: C#CCOc1cc(F)cc(F)c1
Yield: 67 %

Procedure:
This compound was prepared analogously to 2,4-difluoro-2-propynyloxybenzene but using 3,5-difluoro-phenol (14 g, 107 mmol) to give 1,3-difluoro-5-prop-2-ynyloxy-benzene 12 g (67%).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13])[CH:8]=O)([CH3:4])([CH3:3])[CH3:2].[CH3:18][N:19]([CH3:27])[N:20]1[C:24](=[O:25])[CH2:23][S:22][C:21]1=[S:26]>>[CH3:4][C:1]([C:5]1[CH:6]=[C:7]([CH:8]=[C:23]2[S:22][C:21](=[S:26])[N:20]([N:19]([CH3:27])[CH3:18])[C:24]2=[O:25])[CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13])([CH3:2])[CH3:3]
Reactant: CN(C)N1C(=O)CSC1=S
Reactant: CC(C)(C)c1cc(C=O)cc(C(C)(C)C)c1O
Product: CN(C)N1C(=O)C(=Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)SC1=S
Yield: 65 %

Procedure:
The title compound was prepared in 65% yield from 3,5-di-tert-butyl-4-hydroxybenzaldehyde and N-dimethylaminorhodanine following the procedure of Example 1.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH3:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH:20][CH2:21][CH2:22][CH2:23]CCCCC>>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: C=CCCCCCCCC
Reactant: CCCCCCCCC=CCCCCCCCC
Product: C=CCCCCCCCCCCCCCCCCCCCCC
Reaction time: 0.08 h

Procedure:
Example 1 was repeated, with the difference that 20 ml. of 1-decene was utilized in place of 9-octadecene. Within 5 minutes, 4.8% by weight of tricosene was formed and within 30 minutes, 5.7% by weight of tricosene was obtained.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[O:7][CH2:8][C:9]([CH3:12])([CH3:11])[N:10]=2)=[CH:2]1.C([Li])(CC)C.[C:18]1([C:23](Cl)=[O:24])[S:22][CH:21]=[CH:20][CH:19]=1.CO>CCOCC.O1CCCC1>[C:18]1([C:23]([C:2]2[S:1][CH:5]=[CH:4][C:3]=2[C:6]2[O:7][CH2:8][C:9]([CH3:12])([CH3:11])[N:10]=2)=[O:24])[S:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)c1cccs1
Reactant: CC1(C)COC(c2ccsc2)=N1
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CO
Product: CC1(C)COC(c2ccsc2C(=O)c2cccs2)=N1
Reaction time: 1 h
Yield: 87.1 %

Procedure:
2.0 g of 2-(3-thienyl)-4,4-dimethyloxazoline was dissolved in 50 ml of ether, and 10 ml of s-butyllithium (1.3M, cyclohexane solution) was added dropwise thereto at -70° C. The solution was stirred for 1 hour. The reaction solution was added dropwise to a solution of 2.4 g of 2-thenoyl chloride in 50 ml of tetrahydrofuran at -78° C., and the solution was stirred for 30 minutes. Thereafter, 1 ml of methanol was added to the solution, and the reaction solution was concentrated. After adding water thereto, the solution was extracted with chloroform. The chloroform layer was dried and concentrated, and the residue was purified by silica gel chromatography to obtain 2.8 g of 2-(2-thenoyl)-3-(4,4-dimethyl-2-oxazoline-2-yl)thiophene.