Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH3:3][C@@H:4]([OH:8])[C@H:5]([OH:7])[CH3:6].F[C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[C:12]([C:18]([F:21])([F:20])[F:19])[CH:11]=1>C1COCC1>[CH3:3][C@H:4]([O:8][C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[C:12]([C:18]([F:19])([F:21])[F:20])[CH:11]=1)[C@@H:5]([O:7][C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[C:12]([C:18]([F:21])([F:20])[F:19])[CH:11]=1)[CH3:6]
Reactant: N#Cc1ccc(F)cc1C(F)(F)F
Reactant: C[C@@H](O)[C@@H](C)O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C[C@H](Oc1ccc(C#N)c(C(F)(F)F)c1)[C@H](C)Oc1ccc(C#N)c(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
The NaH was suspended in 15 ml of dry THF at 0° C. under N2 gas, then (2R,3R)-2,3-butanediol (0.23 g, 2.46 mmol) was added, this mixture was stirred at 0° C. under N2 for 10 min before adding 4-fluoro-2-(trifluoromethyl)-benzonitrile (1.0 g, 5.18 mmol) The reaction mixture was stirred at 0° C. for 2 hours, then RT(room temperature) for 1 hour. It was quenched with 50 ml of distilled water, extracted with ethyl acetate (3×30 ml), the organic layer was washed with saturated NaHCO3 (three times), the solvent was removed to yield the crude product, it was purified by silica gel column with hexane:ethyl acetate=5:1 as the elute.
Reaction SMILES: C[O:2][C:3](=[O:43])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2([C:34](=[O:42])[NH:35][CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:16][CH2:15][N:14]([C:17](=[O:33])[CH:18]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)[CH2:13][CH2:12]2)=[CH:6][CH:5]=1.[OH-].[Na+]>C1COCC1.CO>[C:29]([O:28][C:26]([NH:25][C@@H:18]([CH2:19][C:20]1[S:21][CH:22]=[CH:23][CH:24]=1)[C:17]([N:14]1[CH2:15][CH2:16][C:11]([CH2:10][C:7]2[CH:6]=[CH:5][C:4]([C:3]([OH:43])=[O:2])=[CH:9][CH:8]=2)([C:34](=[O:42])[NH:35][CH:36]2[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]2)[CH2:12][CH2:13]1)=[O:33])=[O:27])([CH3:32])([CH3:30])[CH3:31]
Reactant: COC(=O)c1ccc(CC2(C(=O)NC3CCCCC3)CCN(C(=O)C(Cc3cccs3)NC(=O)OC(C)(C)C)CC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H](Cc1cccs1)C(=O)N1CCC(Cc2ccc(C(=O)O)cc2)(C(=O)NC2CCCCC2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-[1-(2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl)-4-cyclohexylcarbamoyl-piperidin-4-ylmethyl]-benzoic acid methyl ester (4.46 mmol; 2.73 g) in THF (30 mL) and methanol (10 mL) was added a 1M solution of sodium hydroxide (6.69 mmol; 6.69 mL) and the resulting mixture was stirred overnight at room temperature. The resulting mixture was then evaporated and water (20 mL) was added. A 1N hydrochloric acid solution (10 mL) was added dropwise. A precipitate formed that was separated via filtration to yield 4-[1-(2-(S)-tert-butoxycarbonylamino-3-thiophen-2-yl-propionyl)-4-cyclohexylcarbamoyl-piperidin-4-ylmethyl]-benzoic acid after drying. MS (ESI) m/z 598.23 [M+H]+.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[F:28]>>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:10]3[N:9]4[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]4=[C:7]([CH3:16])[C:6]=3[CH:5]=[C:4]([F:17])[CH:3]=2)=[CH:21][C:20]=1[F:28]
Reactant: OB(O)c1ccc(Cl)c(F)c1
Reactant: Cc1c2n(c3c(Br)cc(F)cc13)CCNC2=O
Product: Cc1c2n(c3c(-c4ccc(Cl)c(F)c4)cc(F)cc13)CCNC2=O

Procedure:
The title compound, white solid (57 mg, 66%), MS (ISP) m/z=347.5 [(M+H)+], mp 216° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-fluoro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 14) (74.3 mg, 0.25 mmol) and commercially available 4-chloro-3-fluoro-phenylboronic acid (56.7 mg, 0.325 mmol).
Reaction SMILES: [H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C:4]1=[O:12].Cl[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:18][CH2:17]1>CN(C=O)C>[C:23]1([CH2:22][N:19]2[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][N:3]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH2:5][C:4]3=[O:12])[CH2:17][CH2:18]2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: ClCCN1CCN(Cc2ccccc2)CC1
Reactant: O=C1Cc2ccccc2N1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1Cc2ccccc2N1CCN1CCN(Cc2ccccc2)CC1
Temperature: 80 °C
Yield: 39 %

Procedure:
Sodium hydride (80% dispersion in mineral oil, 250 mg) was added to a solution of 1,3-dihydro-2H-indol-2-one (1.12 g) in dry DMF (5 ml at 0° C. The mixture was allowed to warm to room temperature and after 50 minutes a solution of 1-(2-chloroethyl)-4-(phenylmethyl)piperazine (2.02 g) in dry DMF (6 ml) was added. The reaction mixture was then heated at 80° C. for 2 hours and then evaporated to dryness under reduced pressure. The residue was purified by flash chromatography on silica gel to afford the title compound (1.1 g, 40%) as an oil.
Reaction SMILES: [CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.O[C:7]1[CH:8]=[C:9]([CH:14]=[C:15]([N:17]2[CH2:21][CH2:20][CH2:19][C:18]2=[O:22])[CH:16]=1)[C:10]([O:12][CH3:13])=[O:11]>>[CH:1]1([O:5][C:7]2[CH:8]=[C:9]([CH:14]=[C:15]([N:17]3[CH2:21][CH2:20][CH2:19][C:18]3=[O:22])[CH:16]=2)[C:10]([O:12][CH3:13])=[O:11])[CH2:4][CH2:3][CH2:2]1
Reactant: OC1CCC1
Reactant: COC(=O)c1cc(O)cc(N2CCCC2=O)c1
Product: COC(=O)c1cc(OC2CCC2)cc(N2CCCC2=O)c1

Procedure:
Prepared in an analogous manner to D14 (first part of synthesis) from cyclobutanol and methyl 3-hydroxy-5-(2-oxopyrrolidin-1-yl)-benzoate (D41).
Reaction SMILES: C(O[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]C)(=O)C(C)=C.C(OCCCCCCCC)(=O)C(C)=C>>[CH3:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH3:7]
Reactant: C=C(C)C(=O)OCCCCCCCCCCCC
Agent: C=C(C)C(=O)OCCCCCCCC
Product: CCCCCCCCCCC

Procedure:
Black-colored colorant particles having a polystyrene core and a polypyrrole shell were produced and the surfaces thereof were hydrophobized in the same manner as in Example 10 except that the dodecyl methacrylate used for the hydrophobization was replaced by octyl methacrylate (manufactured by Tokyo Chemical Industry Co., Ltd.). The resultant is subjected to a centrifugation and a solvent substitution, to thereby obtain an undecane dispersion [12A] of black-colored colorant particles having a polystyrene core and a polypyrrole shell. The particle concentration of the undecane dispersion [12A] was adjusted to 20% by mass, to thereby obtain a black ink [12B] as an ink for an EW element.
Reaction SMILES: [F:1][C:2]1[C:21]([I:22])=[CH:20][C:5]2[C:6]3[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][C:7]=3[CH:16]3[CH2:19][CH:18]([C:4]=2[CH:3]=1)[CH2:17]3.[C:23](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[F:1][C:2]1[C:21]([I:22])=[CH:20][C:5]2[C:6]3[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]([CH3:23])[C:7]=3[CH:16]3[CH2:19][CH:18]([C:4]=2[CH:3]=1)[CH2:17]3
Reactant: CCOC(=O)c1nc2c([nH]1)C1CC(C1)c1cc(F)c(I)cc1-2
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CCOC(=O)c1nc2c(n1C)C1CC(C1)c1cc(F)c(I)cc1-2
Temperature: 40 °C
Yield: 94.1 %

Procedure:
To a pressure tube containing a solution of ethyl 8-fluoro-9-iodo-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate (400 mg at 69% purity) in N,N-dimethylformamide (0.5 mL) was introduced potassium carbonate (134 mg, 0.97 mmol) and methyl iodide (207 mg, 1.46 mol). The pressure tube was closed under an atmosphere of nitrogen and the reaction mixture warmed to 40° C. for 2.5 hr and room temperature for 12 hr. After concentrating the reaction mixture in vacuo, the residue was suspended in ethyl acetate (30 mL) and washed with saturated aqueous sodium bicarbonate (2×10 m), water (2×10 ml) and brine (10 mL). The organic extract was dried over sodium sulfate, filtered and evaporated in vacuo to furnish the crude title compound (389 mg of 77% purity LCMS-UV215) as an orange-brown sticky solid which was used for the next step without further purification. For characterisation purposes, some of the crude product was taken and suspended in ethyl acetate by sonnication and the product, an off-white solid, collected by filtration: 1H NMR (500 MHz, CDCl3) δ 1.48 (t, J=7.09 Hz, 3H), 1.69-1.74 (m, 2H), 2.92-3.00 (m, 2H), 3.50 (td, J=7.57, 3.78 Hz, 1H), 3.56 (td, J=8.35, 3.78 Hz, 1H), 3.94 (s, 3H), 4.46 (q, J=7.15 Hz, 2H), 6.79 (d, J=8.83 Hz, 1H), 8.83 (d, J=6.62 Hz, 1H); M+1=427.
Reaction SMILES: [Cl:1][C:2]1[C:3](F)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH2:10]([C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=1[S:22](=[O:36])(=[O:35])[NH:23][CH2:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH3:34])[N:29]=[CH:28]2)[C:15]([O:17][CH3:18])=[O:16])[CH3:11]>>[Cl:1][C:2]1[C:3]([N:23]([CH2:24][C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([CH3:34])[N:29]=[CH:28]3)[S:22]([C:21]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=2[CH2:10][CH3:11])(=[O:36])=[O:35])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CCc1cc(C(=O)OC)ccc1S(=O)(=O)NCc1ccc2c(cnn2C)c1
Reactant: Fc1ncc(Cl)cc1Cl
Product: CCc1cc(C(=O)OC)ccc1S(=O)(=O)N(Cc1ccc2c(cnn2C)c1)c1ncc(Cl)cc1Cl

Procedure:
The titled compound was prepared according to the procedure described in step-2 of Example 1 from 3,5-dichloro-2-fluoropyridine and methyl 3-ethyl-4-(N-((1-methyl-1H-indazol-5-yl)methyl)sulfamoyl)benzoate (step-2 of Example 4).
Reaction SMILES: [N+:1]([C:4]1[CH:22]=[CH:21][C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:10]=2)=[CH:6][CH:5]=1)([O-])=O.[Cl-].[NH4+].C(O)C.CN(C)C=O>[Fe].O>[C:15]1([C:11]2[CH:10]=[C:9]([O:8][C:7]3[CH:6]=[CH:5][C:4]([NH2:1])=[CH:22][CH:21]=3)[CH:14]=[CH:13][N:12]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ccnc(-c3ccccc3)c2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCO
Product: Nc1ccc(Oc2ccnc(-c3ccccc3)c2)cc1
Yield: 104.6 %

Procedure:
4-(4-nitrophenoxy)-2-phenylpyridine (490 mg), iron powder (1 g), ammonium chloride (2 g), ethanol (10 ml), dimethylformamide (10 ml) and water (5 ml) were stirred at 100° C. for 10 minutes. The mixture was filtered with celite, water was added to the filtrate, and extraction was performed with ethyl acetate. The organic layer was washed 5 times with water, and then the solvent was distilled off under reduced pressure to obtain 4-(2-phenylpyridin-4-yl)oxyaniline (460 mg) as a brown oil.
Reaction SMILES: [C:1]([O:4][CH:5]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([OH:13])=O)[C:6]1=[O:14])(=[O:3])[CH3:2].[CH3:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH:18]([CH3:22])[N:17]1[CH2:23][CH2:24][NH2:25]>O1CCCC1>[CH3:15][C@H:16]1[CH2:21][CH2:20][CH2:19][C@@H:18]([CH3:22])[N:17]1[CH2:23][CH2:24][NH:25][C:11](=[O:13])[CH2:10][N:7]1[CH2:8][CH2:9][CH:5]([O:4][C:1](=[O:3])[CH3:2])[C:6]1=[O:14]
Reactant: CC1CCCC(C)N1CCN
Reactant: CC(=O)OC1CCN(CC(=O)O)C1=O
Solvent: C1CCOC1
Product: CC(=O)OC1CCN(CC(=O)NCCN2[C@H](C)CCC[C@@H]2C)C1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.0 g of (R/S)-2-(3-acetoxy-2-oxo-1-pyrrolidinyl)acetic acid is placed in 15 ml of absolute tetrahydrofuran, whereupon 0.89 g of N,N'-carbonyldiimidazole is added in one portion. The mixture is stirred at room temperature until the gas evolution is complete. Thereafter, 0.86 g of 94.7% cis-(2-(2,6-dimethyl-1-piperidinyl)ethylamine is added and the mixture is left to stand overnight at room temperature and then evaporated. The residue is chromatographed on 60 g of aluminum oxide (activity grade III, neutral). The (R/S)-cis-N-[2-(2,6-dimethyl-1-piperidinyl)ethyl]-2-(3-acetoxy-2-oxo-1-pyrrolidinyl)acetamide which is eluted with methylene chloride has a melting point of 121°-122° after trituration with diethyl ether.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[NH2:5].[CH2:17]([O:24][CH2:25][C@H:26]([NH:30]C(OC(C)(C)C)=O)[C:27](O)=[O:28])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[NH2:30][C@@H:26]([CH2:25][O:24][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:27]([NH:5][C:4]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[C:2]([Cl:1])[CH:3]=1)=[O:28]
Reactant: Nc1ccc(Oc2ccc(Cl)cc2)c(Cl)c1
Reactant: CC(C)(C)OC(=O)N[C@@H](COCc1ccccc1)C(=O)O
Product: N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(Cl)cc2)c(Cl)c1
Yield: 89 %

Procedure:
Proceeding as in Reference 5, but substituting 3-chloro-4-(4-chlorophenoxy)aniline and (S)-3-(benzyloxy)-2-(tert-butoxycarbonylamino)propanoic acid, gave (S)-2-amino-3-(benzyloxy)-N-(3-chloro-4-(4-chlorophenoxy)phenyl)propanamide (80 mg, 89%).
Reaction SMILES: [CH:1]1([CH:7]=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:9][CH2:10][CH:11]([CH2:14][OH:15])[CH2:12][OH:13]>>[CH:1]1([CH2:7][NH:9][CH2:10][CH:11]([CH2:14][OH:15])[CH2:12][OH:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=CC1CCCCC1
Reactant: NCC(CO)CO
Product: OCC(CO)CNCC1CCCCC1

Procedure:
In a manner similar to Preparation 8, react cyclohexanecarboxaldehyde with 2-aminomethyl-1,3-propanediol to obtain the title compound.
Reaction SMILES: [F:1][CH2:2][C:3]1[C:4]([C:9]([O:11]C)=O)=[N:5][CH:6]=[CH:7][N:8]=1.[CH2:13]([C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][C:23]=1[C:24]([O:33][CH3:34])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])[NH2:20])[CH:14]([CH3:16])[CH3:15].C[O-].[Na+].Cl>CO>[CH2:13]([C:17]1[CH:18]=[C:19]([NH:20][C:9]([C:4]2[C:3]([CH2:2][F:1])=[N:8][CH:7]=[CH:6][N:5]=2)=[O:11])[CH:21]=[CH:22][C:23]=1[C:24]([O:33][CH3:34])([C:25]([F:28])([F:26])[F:27])[C:29]([F:30])([F:31])[F:32])[CH:14]([CH3:16])[CH3:15]
Reactant: COC(c1ccc(N)cc1CC(C)C)(C(F)(F)F)C(F)(F)F
Reactant: COC(=O)c1nccnc1CF
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COC(c1ccc(NC(=O)c2nccnc2CF)cc1CC(C)C)(C(F)(F)F)C(F)(F)F
Temperature: 60 °C
Yield: 66.3 %

Procedure:
Methyl 3-fluoromethylpyrazine-2-carboxylate (390 mg, 2.29 mmol) and 3-isobutyl-4-[1-methoxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]aniline (750 mg, 2.29 mmol) were stirred, followed by adding a 28% by weight methanol solution of sodium methoxide (4.4 g, 22.9 mmol), heating at 60° C. for 3 hours while stirring, pouring into a diluted HCl solution, extracting with ethyl acetate and washing with water. The reaction solution was dried over magnesium sulfate, and concentrated under reduced pressure, and then the residue was purified by using silica gel chromatography (hexane:ethyl acetate=3:1) to obtain 0.71 g of the desired compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[S:12][C:11]([CH:13]=[CH:14][C:15]([OH:17])=O)=[CH:10][CH:9]=1.[NH:18]1[CH2:23][CH2:22][NH:21][CH2:20][C:19]1=[O:24]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[S:12][C:11]([CH:13]=[CH:14][C:15]([N:21]2[CH2:22][CH2:23][NH:18][C:19](=[O:24])[CH2:20]2)=[O:17])=[CH:10][CH:9]=1
Reactant: O=C1CNCCN1
Reactant: O=C(O)C=Cc1ccc(-c2ccccc2F)s1
Product: O=C1CN(C(=O)C=Cc2ccc(-c3ccccc3F)s2)CCN1

Procedure:
The compound was prepared analogously to Example 4(b) using 150 mg (0.6 mmol) of 3-[5-(2-fluoro-phenyl)-thiophen-2-yl]-acrylic acid and 54.2 mg (0.54 mmol) of piperazin-2-one. Yield: 109 mg.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[K+].[CH:14]([B-](F)(F)F)=[CH2:15]>C(O)CC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:14]([C:2]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[CH2:15]
Reactant: COC(=O)c1ccc(C)cc1Br
Reactant: C=C[B-](F)(F)F
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [K+]
Solvent: CCCO
Product: C=Cc1cc(C)ccc1C(=O)OC
Temperature: 100 °C
Yield: 61.3 %

Procedure:
A mixture of methyl 2-bromo-4-methylbenzoate (1.06 g, 4.63 mmol), vinyltrifluoroborate potassium salt (621 mg, 4.63 mmol), Pd(dppf)Cl2 (203 mg, 0.28 mmol) and TEA (1.40 g, 13.89 mmol) in n-PrOH (11 mL) was purged with nitrogen, and heated to 100° C. for 2 h. It was then cooled to room temperature and filtered, the filtrate was extracted with ethyl acetate twice. Organic extract was concentrated and purified by flash column chromatograph to give 500 mg of the title compound (60%). 1H NMR (400 MHz, CDCl3): δ 2.40 (3H, s), 3.88 (3H, s), 5.33 (1H, dd, J=1.2 Hz, 10.8 Hz), 5.62 (1H, dd, J=1.2 Hz, 17.6 Hz), 7.12 (1H, d, J=8.0 Hz), 7.37 (1H, s), 7.48 (1H, dd, J=10.8 Hz, 17.6 Hz), 7.80 (1H, d, J=8.0 Hz).
Reaction SMILES: [Na].N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[NH4+].ClCCCS([O-])(=O)=O.[Na+].[C:33]1([P:39]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:40][CH2:41][CH2:42][S:43]([O-:46])(=[O:45])=[O:44])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[Na+].[Cl-].[Na+].FC(F)(F)C(O)=O>O1CCCC1>[C:47]1([P:39]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:40][CH2:41][CH2:42][S:43]([OH:46])(=[O:45])=[O:44])[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1
Reactant: O=S(=O)([O-])CCCP(c1ccccc1)c1ccccc1
Agent: N
Agent: O=S(=O)([O-])CCCCl
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: O=S(=O)(O)CCCP(c1ccccc1)c1ccccc1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
The compound 3-(diphenylphosphino)propanesulfonic acid was produced by the following procedure. To a solution of 3.8 g of sodium in 500 ml of liquid ammonia in a stirred reaction vessel maintained at -78° C. by cooling, 21.8 g of triphenylphosphine was added. After 30 minutes, 4.3 g of ammonium chloride was added and after an additional 30 minutes, 15 g of sodium 3-chloropropanesulfonate was added. The cooling was stopped and 400 ml of tetrahydrofuran was added to the reaction mixture. After the ammonia was evaporated, the mixture was refluxed for some time and then evaporated. The residue thereby obtained was washed with hot ethanol and the product was dried in vacuo to yield a mixture of sodium 3-(diphenylphosphino)propanesulfonate and sodium chloride. The mixture was treated with aqueous trifluoroacetic acid to afford the 3-(diphenylphosphino)propanesulfonic acid.
Reaction SMILES: [CH3:1][C:2]1[C:3]2[CH:10]=[C:9]([N+:11]([O-])=O)[CH:8]=[CH:7][C:4]=2[S:5][CH:6]=1>CO.[Pd]>[CH3:1][C:2]1[C:3]2[CH:10]=[C:9]([NH2:11])[CH:8]=[CH:7][C:4]=2[S:5][CH:6]=1
Reactant: Cc1csc2ccc([N+](=O)[O-])cc12
Agent: [Pd]
Solvent: CO
Product: Cc1csc2ccc(N)cc12
Reaction time: 8.5 h
Yield: 38.6 %

Procedure:
To a solution of 3-methyl-5-nitro-benzo[b]thiophene [18] (95 mg, 0.492 mmol) in methanol (20 mL) was added 5% palladium on carbon (20 mg) and the mixture was stirred under 1 atm H2 for 8.5h. The mixture was filtered through celite and the filtrate evaporated. The residue was passed through a silica plug to afford 3-methyl-benzo[b]thiophen-5-ylamine as a dark orange solid (31 mg, 39%), single spot at Rf 0.31 (4:1 hexane:ethyl acetate). 1H NMR (CDCl3): δ 7.60 (1H, d, J=8.4 Hz), 7.02 (1H, s), 7.00 (1H, d, J=2.2 Hz), 6.79 (1H, dd, J=8.4, 2.2 Hz), 2.37 (3H, s).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:12][NH:13][CH:14]=O.C(NC(C)C)(C)C.P(Cl)(Cl)(Cl)=O.C(=O)([O-])O.[Na+]>ClCCl>[Cl:1][C:2]1[C:7]([C:8]([F:10])([F:11])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:12][N+:13]#[C-:14]
Reactant: O=CNCc1cccc(C(F)(F)F)c1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(C)NC(C)C
Solvent: O=P(Cl)(Cl)Cl
Product: [C-]#[N+]Cc1cccc(C(F)(F)F)c1Cl
Temperature: 3.5 °C
Reaction time: 2 h
Yield: 106.6 %

Procedure:
A solution of {[2-chloro-3-(trifluoromethyl)phenyl]methyl}formamide (0.67 g, 2.82 mmol) in anhydrous dichloromethane (20 ml) was cooled under argon in an ice-water bath before the addition of diisopropylamine (1.78 ml, 12.7 mmol) followed by phosphorus oxychloride (0.393 ml, 4.23 mmol). The reaction was stirred at between 2-5° C. for 2 hrs. The mixture was then reduced in vacuo and the residue treated with saturated aqueous sodium hydrogen carbonate (20 ml) and extracted with dichloromethane (20 ml). The organic layer was passed through a hydrophobic frit and the reduced in vacuo to give a yellow solid. Further drying in vacuo gave [2-chloro-3-(trifluoromethyl)phenyl]methyl isocyanide as an orange gum (0.66 g) which was used without further purification.
Reaction SMILES: CO[C:3]([C:5]1[N:6]([CH3:22])[S:7](=[O:21])(=[O:20])[C:8]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:9]=2[C:10]=1[OH:11])=[O:4].[NH2:23][C:24]1[S:25][C:26]([CH3:29])=[CH:27][N:28]=1>C1(C)C(C)=CC=CC=1>[OH:11][C:10]1[C:9]2[CH:12]=[CH:13][C:14]3[C:19]([C:8]=2[S:7](=[O:20])(=[O:21])[N:6]([CH3:22])[C:5]=1[C:3]([NH:23][C:24]1[S:25][C:26]([CH3:29])=[CH:27][N:28]=1)=[O:4])=[CH:18][CH:17]=[CH:16][CH:15]=3
Reactant: Cc1cnc(N)s1
Reactant: COC(=O)C1=C(O)c2ccc3ccccc3c2S(=O)(=O)N1C
Solvent: Cc1ccccc1C
Product: Cc1cnc(NC(=O)C2=C(O)c3ccc4ccccc4c3S(=O)(=O)N2C)s1
Yield: 67 %

Procedure:
4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide was prepared analogous to Example 22 from 4-hydroxy-2-methyl-2H-Naphtho[ 2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester-1,1-dioxide and 2-amino-5-methyl-thiazole. Yield: 67% of theory, m.p. 249°-250° C (decomp.; from xylene).
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:18])[CH:8]=2)[N:3]=1.O.[NH2:20][NH2:21]>>[Cl:18][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([NH:20][NH2:21])[CH:11]=[C:10]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Clc1ccc2nc(Cl)cc(-c3ccccc3)c2c1
Reactant: NN
Solvent: O
Product: NNc1cc(-c2ccccc2)c2cc(Cl)ccc2n1

Procedure:
A stirred mixture of 2,6-dichloro-4-phenylquinoline (2.7 g., 0.01 mole) and hydrazine hydrate (6.8 g.) was refluxed under nitrogen for 1 hour and concentrated in vacuo. The residue was suspended in warm water, and the solid was collected by filtration, dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81 g. (67%) yield) of 6-chloro-2-hydrazino-4-phenylquinoline of melting point 156.5°-157° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[NH3:12]>>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([NH2:12])=[O:5]
Reactant: O=C(Cl)c1c(F)cccc1Cl
Reactant: N
Product: NC(=O)c1c(F)cccc1Cl

Procedure:
2-chloro-6-fluoro-benzamide was prepared from 2-chloro-6-fluoro-benzoic acid chloride and ammonia by processes known from the literature. It had amelting point of 138° C. ##STR7##
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:20]([O:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:6][CH:7]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)Cc1cccc(OCc2ccccc2)c1
Reaction time: 16 h

Procedure:
To a stirred solution of Ethyl 2-(3-hydroxyphenyl)acetate (3 g, 16.6 mmol) in DMF (25 ml) was added potassium carbonate (2.99 g, 21.6 mmol) at room temperature followed by drop wise addition of benzyl bromide (3.13 g, 18.3 mmol). The reaction mixture was stirred for 16 hours and taken in ethyl acetate, washed with water (2×) and brine. The organic layer was dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (hex:ethyl acetate 4:1) to give the title compound.