Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC1C=CC(C[O:7][C:8](=[O:27])[CH2:9][C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH:11]=2)=CC=1.[OH-].[Na+]>C(O)C>[F:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:10]([CH2:9][C:8]([OH:27])=[O:7])=[CH:11]2)=[CH:21][CH:22]=1
Reactant: O=C(Cc1cn(Cc2ccc(F)cc2)c2ccccc12)OCc1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)Cc1cn(Cc2ccc(F)cc2)c2ccccc12

Procedure:
8.7 g (22.2 mMol) [1-(4-fluorobenzyl)indole-3-yl]acetic acid (4-fluorobenzyl)ester are dissolved in 50 ml ethanol. 110 ml 1N sodium hydroxide solution are added and the mixture heated for 1 hour at reflux. After cooling, the aqueous phase is washed with ether, acidulated with concentrated hydrochloric acid and the precipitate filtered.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[Se:19][C:18]([CH:20]=O)=[CH:17][CH:16]=3)=[C:11]([F:22])[CH:10]=2)=[CH:5][CH:4]=1)[CH3:2].CC(C)([O-])C.[K+].O.Cl.[CH2:31]1[CH2:35]O[CH2:33][CH2:32]1>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)CCC>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[Se:19][C:18]([CH:20]=[CH:35][CH2:31][CH2:32][CH3:33])=[CH:17][CH:16]=3)=[C:11]([F:22])[CH:10]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: C1CCOC1
Reactant: CCc1ccc(-c2ccc(-c3ccc(C=O)[se]3)c(F)c2)cc1
Agent: CC(C)(C)[O-]
Agent: CCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: O
Product: CCCC=Cc1ccc(-c2ccc(-c3ccc(CC)cc3)cc2F)[se]1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
22.0 g (54.5 mmol) of butyltriphenylphosphonium bromide are initially introduced together with 17.3 g (48.4 mmol) of 5-(4′-ethyl-3-fluorobiphenyl-4-yl)selenophene-2-carbaldehyde in 700 ml of THF, and a solution of 6.0 g (53.5 mmol) of potassium tert-butoxide in 100 ml of THF is added with ice-cooling. The mixture is stirred at RT for 3 h. Water and 2 N hydrochloric acid are added, and the batch is extracted with MTBE. The organic phase is washed with sat. sodium chloride soln. and dried using sodium sulfate. The solution is concentrated to dryness, and the residue is purified by column chromatography (SiO2, toluene). 2-(4′-Ethyl-3-fluorobiphenyl-4-yl)-5-(pent-1-enyl)selenophene is obtained as an orange solid.
Reaction SMILES: [F:1]C1C=CC2SC(C(O)=O)=CC=2C=1.F[C:15]1[CH:28]=[CH:27][C:18]2[S:19][C:20]([C:22]([S:24][CH2:25][CH3:26])=[S:23])=[CH:21][C:17]=2[CH:16]=1>>[F:1][C:16]1[C:17]2[CH:21]=[C:20]([C:22]([S:24][CH2:25][CH3:26])=[S:23])[S:19][C:18]=2[CH:27]=[CH:28][CH:15]=1
Reactant: O=C(O)c1cc2cc(F)ccc2s1
Reactant: CCSC(=S)c1cc2cc(F)ccc2s1
Product: CCSC(=S)c1cc2c(F)cccc2s1

Procedure:
The 5-fluoro-2-benzo[b]thiophenecarboxylic acid prepared above in A was converted to ethyl 5-fluoro-2-benzo[b]thiophenecarbodithioate (mp 91-92° C.) using the procedures described above in Examples 2(B)-2(D). NMR confirmed the structure as that of ethyl 5-fluoro-2-benzo[b]thiophenecarbodithioate.
Reaction SMILES: [F:1][C:2]1[CH:24]=[C:23]([CH:25]=[O:26])[CH:22]=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]=[CH:9][C:8]=1O)=[O:5].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:24]=[C:23]([CH:22]=[CH:21][C:3]=1[C:4]1[O:5][C:8]2[CH:9]=[CH:10][C:11]([S:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:12][C:7]=2[N:6]=1)[CH:25]=[O:26]
Reactant: O=Cc1ccc(C(=O)Nc2cc(Sc3ccccc3)ccc2O)c(F)c1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: Cc1ccccc1
Product: O=Cc1ccc(-c2nc3cc(Sc4ccccc4)ccc3o2)c(F)c1
Temperature: 130 °C

Procedure:
A mixture of 2-fluoro-4-formyl-N-(2-hydroxy-5-(phenylthio)phenyl)benzamide (0.180 g, 0.490 mmol) and pyridinium p-toluenesulfonate (0.123 g, 0.490 mmol) in 5.0 mL toluene was heated to 130° C. in a sealed tube for a total of 6 h. The reaction was cooled and was partitioned between 1N NaOH and EtOAc. The organic layer was washed 1× brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a solid that was purified by silica gel chromatography, 0-30-60% EtOAc/hexanes to give 3-fluoro-4-(5-(phenylthio)benzo[d]oxazol-2-yl)benzaldehyde as a yellow solid. MS (ESI) m/z: Calculated: 349.1; Observed: 350.0 (M++1).
Reaction SMILES: [C@@H:1]12[O:11][C@@H:2]1CC[C:5]1[C:10]2=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:12](Cl)(Cl)Cl>>[CH3:12][C@@:1]1([C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[O:11][CH2:2]1
Reactant: c1ccc2c(c1)CC[C@H]1O[C@@H]21
Reactant: ClC(Cl)Cl
Product: C[C@]1(c2ccccc2)CO1

Procedure:
(1S,2R)-3,4-Dihydronaphthalene oxide (Table 6, entry 5) Colorless oil, [α]25D=−38.8° (c 0.91, CHCl3).
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([Cl:10])=[CH:4][C:3]=1[SH:11].CN(C=O)C.C([O-])([O-])=O.[K+].[K+].Cl[CH2:24][C:25](=[O:31])[CH2:26][C:27]([O:29][CH3:30])=[O:28]>O>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([Cl:10])=[CH:4][C:3]=1[S:11][CH2:24][C:25](=[O:31])[CH2:26][C:27]([O:29][CH3:30])=[O:28]
Reactant: COC(=O)CC(=O)CCl
Reactant: COc1cc(Cl)cc(S)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CC(=O)CSc1cc(Cl)cc(OC)c1Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of 2,5-dichloro-3-methoxybenzenethiol (2.36 g) and DMF (dry) (60 mL) were added K2CO3 (1.72 g) and methyl 4-chloro-3-oxobutanoate (1.46 mL) at 0° C. The mixture was stirred at room temperature for 2 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed successively with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (3.37 g).
Reaction SMILES: [CH3:1][C:2]1[C:7]([OH:8])=[C:6]([CH2:9][OH:10])[C:5]([CH:11]=[CH2:12])=[CH:4][N:3]=1>[O-2].[O-2].[Mn+4].C(Cl)(Cl)Cl>[CH3:1][C:2]1[C:7]([OH:8])=[C:6]([CH:9]=[O:10])[C:5]([CH:11]=[CH2:12])=[CH:4][N:3]=1
Reactant: C=Cc1cnc(C)c(O)c1CO
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: C=Cc1cnc(C)c(O)c1C=O
Reaction time: 0.5 h

Procedure:
A solution of 10 g. of 2-methyl-3-hydroxy-4-hydroxymethyl-5-vinylpyridine in 300 ml. of hot chloroform was treated with 100 g. of manganese dioxide. After 1/2 hour of stirring, the mixture was filtered and the filtrate was evaporated to dryness to give 2-methyl-3-hydroxy-4-formyl-5-vinylpyridine.
Reaction SMILES: [O:1]1[C:13]2[C:4](=[CH:5][C:6]3[NH:10][C:9]([SH:11])=[N:8][C:7]=3[CH:12]=2)[O:3][CH2:2]1.Cl.Cl[CH2:16][C:17]1[C:22]([CH3:23])=[C:21]([O:24][CH2:25][CH3:26])[C:20]([CH3:27])=[CH:19][N:18]=1.[OH-].[Na+]>C(O)C.O>[CH2:25]([O:24][C:21]1[C:20]([CH3:27])=[CH:19][N:18]=[C:17]([CH2:16][S:11][C:9]2[NH:10][C:6]3[CH:5]=[C:4]4[O:3][CH2:2][O:1][C:13]4=[CH:12][C:7]=3[N:8]=2)[C:22]=1[CH3:23])[CH3:26]
Reactant: Sc1nc2cc3c(cc2[nH]1)OCO3
Reactant: CCOc1c(C)cnc(CCl)c1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCOc1c(C)cnc(CSc2nc3cc4c(cc3[nH]2)OCO4)c1C

Procedure:
5.82 g of 5H-1,3-dioxolo[4,5-f]benzimidazole-6-thiol were suspended in 200 ml of ethanol and the suspension was treated with 7.1 g 2-chloromethyl-4-ethoxy-3,5-dimethylpyridine hydrochloride while cooling with ice. Thereafter, a solution of 2.4 g of sodium hydroxide in 100 ml of water was added dropwise thereto, the mixture was left to boil at reflux overnight and subsequently evaporated to dryness in vacuo. The residue was dissolved in 500 ml of methylene chloride. The solution was washed firstly with 250 ml of 1.5N sodium hydroxide solution and then with 3×300 ml of water, dried over sodium sulfate and evaporated in vacuo. The product was purified on 150 g of silica gel using ethyl acetate/methylene chloride (1:1) as the elution agent. Crystallization from acetonitrile gave 6-[[(4-ethoxy-3,5-dimethyl-2-pyridyl)methyl]thio]-5H-1,3-dioxolo[4,5-f]benzimidazole of melting point 184°-185°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[C:9](OC(=O)C)(=[O:11])[CH3:10]>>[C:9]([NH:5][C:4]1[CH:6]=[CH:7][CH:8]=[C:2]([Cl:1])[CH:3]=1)(=[O:11])[CH3:10]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cccc(Cl)c1
Product: CC(=O)Nc1cccc(Cl)c1
Temperature: 90 °C
Reaction time: 4 h
Yield: 226.8 %

Procedure:
To 3-chloroaniline (10 g, 0.078 mol) was added portionwise acetic anhydride (32 g, 0.314 mol) in such a manner as to keep the temperature of the reaction mixture below 85° C. The reaction mixture was then stirred at 90° C. for 4 hours and then cooled to room temperature. The reaction mixture was then poured carefully into ice water, extracted with ethyl acetate and dried over sodium sulfate. The solvent was removed, yielding 30 g of N-acetyl-3-chloroaniline.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:35]=[C:34]3[C:30]([C:31]([NH:44][C:45](=[O:49])[CH2:46][CH2:47][CH3:48])=[N:32][N:33]3COCC[Si](C)(C)C)=[CH:29][CH:28]=2)=[CH:23][CH:22]=1.C(OCC)(=O)C>O1CCCC1>[CH3:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:35]=[C:34]3[C:30]([C:31]([NH:44][C:45](=[O:49])[CH2:46][CH2:47][CH3:48])=[N:32][NH:33]3)=[CH:29][CH:28]=2)=[CH:25][CH:26]=1
Reactant: CCCC(=O)Nc1nn(COCC[Si](C)(C)C)c2cc(-c3ccc(OC)cc3)ccc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCC(=O)Nc1n[nH]c2cc(-c3ccc(OC)cc3)ccc12
Temperature: 66 °C

Procedure:
13.6 cm3 of tetrabutylammonium fluoride as a 1M solution in tetrahydrofuran are added to 1 g of N-[6-(4-methoxyphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described previously, in 30 cm3 of tetrahydrofuran, and the reaction medium is then heated at about 66° C. for 19 hours. The heating is then stopped and 75 cm3 of ethyl acetate are added. This mixture is washed with 2×50 cm3 of saturated aqueous sodium hydrogen carbonate solution and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with an ethyl acetate/cyclohexane mixture (60/40 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 10 cm3 of diisopropyl ether, filtered and washed with 2×5 cm3 of diisopropyl ether and then with 2×5 cm3 of ethyl acetate; after drying (90 Pa; 50° C.), 500 mg of N-[6-(4-methoxyphenyl)-1H-indazol-3-yl]butanamide are obtained in the form of a white product melting at 210° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]2[N:9]=[C:10]([CH:12]([CH3:14])[CH3:13])[CH:11]=[C:7]2[C:6]([C:15]2[CH:16]=[CH:17][C:18](=[O:21])[NH:19][N:20]=2)=[CH:5][CH:4]=1>[Zn].C(O)(=O)C>[CH3:1][O:2][C:3]1[N:8]2[N:9]=[C:10]([CH:12]([CH3:14])[CH3:13])[CH:11]=[C:7]2[C:6]([C:15]2[CH2:16][CH2:17][C:18](=[O:21])[NH:19][N:20]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(-c2ccc(=O)[nH]n2)c2cc(C(C)C)nn12
Agent: [Zn]
Solvent: CC(=O)O
Product: COc1ccc(C2=NNC(=O)CC2)c2cc(C(C)C)nn12
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 35.3 %

Procedure:
A mixture of the compound of Example 276 (45 mg), zinc (52 mg) and acetic acid (1.6 mL) was stirred at 100° C. for 30 min. The insoluble material was removed by filtration and the filtrate was concentrated. A saturated sodium bicarbonate solution was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed sequentially with 0.1 mol/LEDTA disodium solution and saturated brine and dried over magnesium sulfate. The solvent was concentrated and the resulting residue was purified by silica gel column chromatography (methanol:ethyl acetate=1:9) to afford the title compound as a pale yellow oil (16 mg).
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].S(=O)(=O)(O)O.[OH:13][C@H:14]([CH3:27])[CH2:15][C:16]#[C:17][CH2:18][O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)(O)[O-].[Na+]>O>[C:1]([O:13][C@H:14]([CH3:27])[CH2:15][C:16]#[C:17][CH2:18][O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: C[C@@H](O)CC#CCOCc1ccccc1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: CC(=O)O[C@H](C)CC#CCOCc1ccccc1
Temperature: 60 °C
Yield: 98.2 %

Procedure:
Next, acetic anhydride (23.6 ml, 0.25 mole) and sulfuric acid (0.13 ml) were added to stirred 5-(R)-hydroxy-1-benzyloxy-2-hexyne (34 g, 0.17 mole), prepared above, at 25° C., and the reaction was heated to 60° C. for 20 hours. Water (100 ml) was added, followed by solid sodium bicarbonate (33 g, 0.40 mole) in portions. The reaction mixture was extracted with ethyl acetate (80 ml), the solvent dried (magnesium sulfate) and evaporated to afford 5-(R)-acetoxy-1-benzyloxy-2-hexyne (41.1 g, 99% yield) as a brown oil.
Reaction SMILES: NC1S[C:4]2[C:9](=[O:10])[NH:8][C:7]([NH2:11])=[N:6][C:5]=2[N:12]=1.NC1NC(=O)C=C(N)N=1.[Br:22]Br.C([O-])(=O)C.[Na+]>C(O)(=O)C>[NH2:11][C:7]1[NH:8][C:9](=[O:10])[C:4]([Br:22])=[C:5]([NH2:12])[N:6]=1
Reactant: BrBr
Reactant: Nc1nc2nc(N)sc2c(=O)[nH]1
Agent: CC(=O)[O-]
Agent: Nc1cc(=O)[nH]c(N)n1
Agent: [Na+]
Solvent: CC(=O)O
Product: Nc1nc(N)c(Br)c(=O)[nH]1

Procedure:
FIG. 21 shows the method of synthesis of 2,5-diamino-6H-thiazolo[4,5-d]pyrimidin-7-one 14. 2,6-diamino-3H-pyrimidin-4-one 1 was reacted with Br2 in the presence of sodium acetate and acetic acid to produce 2,6-diamino-5-bromopyrimidin-4-one 13. 2,6-diamino-5-bromopyrimidin-4-one 13 was then reacted with CN2SH4 in ethanol to produce 2,5-diamino-6H-thiazolo[4,5-d]pyrimidin-7-one 14.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=[O:15])[N:8]([CH2:16][CH2:17][CH2:18]Cl)[CH2:7][CH2:6]2.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH2:30][CH2:31][NH:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29].C(=O)([O-])[O-].[K+].[K+].C(Cl)(Cl)Cl.CO>ClC1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=[O:15])[N:8]([CH2:16][CH2:17][CH2:18][N:32]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:31][CH2:30][C:24]1[CH:25]=[CH:26][C:27]([O:28][CH3:29])=[C:22]([O:21][CH3:20])[CH:23]=1)[CH2:7][CH2:6]2
Reactant: COc1ccc(CCNCc2ccccc2)cc1OC
Reactant: COc1cc2c(cc1OC)C(=O)N(CCCCl)CC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Clc1ccccc1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COc1ccc(CCN(CCCN2CCc3cc(OC)c(OC)cc3C2=O)Cc2ccccc2)cc1OC

Procedure:
1-[6,7-Dimethoxy-3,4-dihydro-2H-isoquinolin-1-one-2-yl]-3-[N-benzyl-N-(2-(3,4-dimethoxy-phenyl)-ethyl)-amino]-propane was prepared analogous to Example 1 (b) by reacting 1-(6,7-dimethoxy-3,4-dihydro-2H-isoquinolin-1-one-2-yl)-3-chloropropane with N-(3,4-dimethoxy-phenylethyl)-N-benzyl-amine in chlorobenzene in the presence of potassium carbonate. Yield: 2.2 gm (69.8% of theory); Rf -value (chloroform/methanol = 19:1): 0.8.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].[C:10]1([CH2:16][CH2:17]O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH2:1]([N:3]([CH2:17][CH2:16][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCNc1ccccc1
Reactant: OCCc1ccccc1
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Solvent: O
Product: CCN(CCc1ccccc1)c1ccccc1
Temperature: 243 °C
Yield: 81 %

Procedure:
182 parts of N-ethylaniline, 244 parts of phenylethyl alcohol and 20 parts of triphenyl phosphite are mixed whilst stirring and next heated to an internal temperature of 206° C, at which the elimination of water commences. The mixture is then heated to an internal temperature of 243° C in the course of 20 hours. During this time, 25 parts of water have distilled off and the condensation has ended. The excess ethylaniline and the unconverted alcohol are then distilled off. 274 parts of N-ethyl-N-phenylethyl-aniline, corresponding to a yield of 81% of theory, distil at a boiling point of 160° C/5 mm Hg.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14](O)=[O:15])(=[O:11])=[O:10])=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=1.Cl.[CH2:26]([O:28][C:29](=[O:35])[C@H:30]([C@@H:32]([CH3:34])[OH:33])[NH2:31])[CH3:27].O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>>[CH2:26]([O:28][C:29](=[O:35])[CH:30]([NH:31][C:14](=[O:15])[C:13]1[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=1[S:9](=[O:11])(=[O:10])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[C:21]([F:22])([F:23])[F:24])[CH:32]([OH:33])[CH3:34])[CH3:27]
Reactant: CCOC(=O)[C@@H](N)[C@@H](C)O
Reactant: O=C(O)c1ccccc1S(=O)(=O)Nc1ccc(F)cc1C(F)(F)F
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)C(NC(=O)c1ccccc1S(=O)(=O)Nc1ccc(F)cc1C(F)(F)F)C(C)O

Procedure:
Under the conditions of Example 2(a), 3.633 g (10 mmol) of 2-[N-(4-Fluoro-2-trifluoromethylphenyl)sulfamoyl]benzoic acid, 1.736 g (10 mmol) of L-threonine ethyl ester hydrochloride, 1.531 g (10 mmol) of hydroxybenzotriazole, hydrate, as well as 1.012 g (10 mmol) of triethylamine and 2.063 g (10 mmol) of dicyclohexylcarbodiimide are reacted and worked up analogously. The crude product is chromatographed on silica gel. The title compound is eluted with ethyl acetate.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[C:17]([O:24][CH2:25][CH3:26])[CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[CH2:25]([O:24][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:16]=1[CH:15]=[C:14]([N:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)[CH:23]=[CH:22]2)[CH3:26]
Reactant: CCOc1cccc2ccc(N3CCN(Cc4ccccc4)CC3)cc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOc1cccc2ccc(N3CCNCC3)cc12

Procedure:
A solution of 24.9 g (0.072 mol) of 1-benzyl-4-(8-ethoxy-naphthalen-2-yl)-piperazine in 360 ml of ethanol is combined with 5 g of palladium on charcoal (10%) and stirred at a hydrogen pressure of 5 bar at ambient temperature. The catalyst is separated off, the filtrate is concentrated by evaporation and the residue is washed with diethylether.
Reaction SMILES: [F:1][C:2]1[C:18]([N+:19]([O-])=O)=[CH:17][CH:16]=[CH:15][C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]([O:13][CH3:14])=[O:12])=[O:5]>CO.[Pd]>[NH2:19][C:18]1[C:2]([F:1])=[C:3]([CH:15]=[CH:16][CH:17]=1)[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]([O:13][CH3:14])=[O:12])=[O:5]
Reactant: COC(=O)[C@@H]1CCCN1C(=O)c1cccc([N+](=O)[O-])c1F
Agent: [Pd]
Solvent: CO
Product: COC(=O)[C@@H]1CCCN1C(=O)c1cccc(N)c1F
Yield: 107 %

Procedure:
A solution of 25.0 g (0.08 mol, 1.0 eq) of methyl (S)-1-(2-fluoro-3-nitrobenzoyl)pyrrolidine-2-carboxylate in 250 ml of methanol in the presence of 7.0 g (28% by weight) of palladium on carbon at 10% was stirred under a hydrogen atmosphere at ambient temperature for 4 days. The reaction medium was filtered through celite and washed with 100 ml of methanol. The filtrate was evaporated. 22.80 g of methyl (S)-1-(3-amino-2-fluorobenzoyl)pyrrolidine-2-carboxylate were obtained in the form of a light oil. Quantitative yield.
Reaction SMILES: [CH:1]([Si:4]([CH:9]([CH3:11])[CH3:10])([CH:6]([CH3:8])[CH3:7])[SH:5])([CH3:3])[CH3:2].[H-].[Na+].Br[C:15]1[CH:16]=[C:17]([CH:23]=[CH:24][C:25]=1[CH3:26])[C:18]([O:20][CH2:21][CH3:22])=[O:19]>C1COCC1.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>[CH2:21]([O:20][C:18](=[O:19])[C:17]1[CH:23]=[CH:24][C:25]([CH3:26])=[C:15]([S:5][Si:4]([CH:1]([CH3:3])[CH3:2])([CH:6]([CH3:8])[CH3:7])[CH:9]([CH3:11])[CH3:10])[CH:16]=1)[CH3:22]
Reactant: CC(C)[Si](S)(C(C)C)C(C)C
Reactant: CCOC(=O)c1ccc(C)c(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)c1ccc(C)c(S[Si](C(C)C)(C(C)C)C(C)C)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a 0° C. stirred solution of triisopropylsilanethiol (14.28 mmol, 3.07 mL) in THF was added sodium hydride (14.28 mmol, 0.57 g of a 60 wt % dispersion in mineral oil). After 30 min, the mixture was added to a solution of ethyl 3-bromo-4-methylbenzoate (10.99 mmol, 2.67 g) at room temperature, followed by tetrakis(triphenylphosphine)palladium(0) (0.55 mmol, 0.64 g). The resulting mixture was warmed to reflux and stirred for 18 hours, then cooled to room temperature and subjected to standard aqueous workup to afford the title compound which was used crude in the next step.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[CH:5][C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:3]1.[Br:15]N1C(=O)CCC1=O>C(#N)C.[O-2].[O-2].[Mn+4]>[Br:15][C:5]1[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:3][N:2]([CH3:1])[C:6]=1[CH:7]=[O:8]
Reactant: Cn1nc(-c2ccccc2)cc1CO
Reactant: O=C1CCC(=O)N1Br
Agent: [Mn+4]
Agent: [O-2]
Solvent: CC#N
Product: Cn1nc(-c2ccccc2)c(Br)c1C=O
Temperature: 25 °C
Reaction time: 40 h
Yield: 63.5 %

Procedure:
A solution of (1-methyl-3-phenyl-1H-pyrazol-5-yl)methanol (1b) (340 mg, 1.81 mmol) and N-bromosuccinimide (338 mg, 1.90 mmol) in acetonitrile (30 mL) was stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuo. Water (10 mL) was added and the aqueous layer was extracted with ethyl acetate (2×12 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was taken in dichloromethane (5 mL) and manganese dioxide (1.57 g, 18.06 mmol) was added. The reaction mixture was stirred at room temperature for 40 hours, filtered over Celite®, and the filtrate was concentrated in vacuo. The residue was dissolved in a minimum of dichloromethane and purified thought a pad of silice, (cyclohexane/ethyl acetate 80/20), to provide 4-bromo-1-methyl-3-phenyl-1H-pyrazole-5-carbaldehyde (1c) (304 mg, 1.15 mmol, 63%).
Reaction SMILES: [CH3:1][C:2]([CH2:4][CH:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]=1[OH:23])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:3].C(=O)([O-])[O-].[Na+:28].[Na+].CC(C)=O.CC(=O)CC>O>[CH3:1][C:2]([CH2:4][CH:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]=1[O-:23])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[Na+:28]
Reactant: CC(=O)CC(c1ccccc1)c1c(O)c2ccccc2oc1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCC(C)=O
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)CC(c1ccccc1)c1c([O-])c2ccccc2oc1=O

Procedure:
Warfarin sodium is prepared by refluxing the pure warfarin acid with an excess of sodium carbonate in a polar solvent such as acetone or butanone, which may be either anhydrous or contain from about 1% to about 10% water. The unreacted sodium carbonate is preferably removed by filtration. The product is isolated by evaporating the solvent to dryness or by precipitating the salt by addition of a nonpolar solvent such as hexane, cyclohexane, heptane and the like, and filtering and drying the precipitate.