Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[CH2:7][CH:6]([CH3:8])[CH2:5][CH2:4][CH:3]1[CH:9]=[O:10].[CH2:12](Br)[CH:13]=[CH2:14].[NH4+].[Cl-]>CCOCC>[CH3:11][C:2]1([CH3:1])[CH2:7][CH:6]([CH3:8])[CH2:5][CH2:4][CH:3]1[C:9](=[O:10])[CH:12]=[CH:13][CH3:14]
Reactant: C=CCBr
Reactant: CC1CCC(C=O)C(C)(C)C1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: CC=CC(=O)C1CCC(C)CC1(C)C
Yield: 80.8 %

Procedure:
2,2,4-Trimethyl-1-cyclohexanecarbaldehyde (11 g, 72 mmole) in ether (100 ml) was added dropwise with stirring to a Grignard compound prepared from Mg (2.3 g) and allylbromide (10 g) in ether and refluxed for 2 h. After cooling, the mixture was hydrolyzed with NH4Cl-solution, then distilled at a bath temperature of 150°/0.5 hPa, to obtain 11.3 g (80%) of the desired product as a 2:1 mixture of 2 isomers.
Reaction SMILES: [CH3:1][C@H:2]1[C@:8]2([CH3:16])[CH2:9][C@H:10]([C:13]([CH3:15])=[CH2:14])[CH2:11][CH2:12][C:7]2=[CH:6][C:4](=[O:5])[CH2:3]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CCOCC>[CH3:1][C@H:2]1[C@:8]2([CH3:16])[CH2:9][C@H:10]([C:13]([CH3:15])=[CH2:14])[CH2:11][CH2:12][C:7]2=[CH:6][C@@H:4]([OH:5])[CH2:3]1
Reactant: C=C(C)[C@@H]1CCC2=CC(=O)C[C@@H](C)[C@]2(C)C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: C=C(C)[C@@H]1CCC2=C[C@@H](O)C[C@@H](C)[C@]2(C)C1

Procedure:
β-Nootkatol was prepared by reduction of 190 mg nootkatone (Fluka) with 20 mg of LiAlH4 in in 5 mL dry ether (diethyl-ether) (Shoji et al., 1984). After stirring the grey suspension for one night, the reaction was stopped by careful addition of Na2SO4.10H2O. The mlxture was stirred for an additional 30 minutes, and dried by the addition of MgSO4. The solids were filtered off and the ether was washed with distilled water. After drying and evaporation of the solvent, 140 mg of a crude oil was obtained that besides β-nootkatol contained 4% of α-nootkatol, EIMS (70 eV) m/z: 220 [M]+ (33), 177 (77), 161 (40), 145 (52), 131 (77), 119 (100), 109 (41), 107 (50), 105 (59), 95 (46), 93 (60), 91 (43), 81 (45), 79 (80), 77 (64), 69 (47), 67 (52), 55 (58), 43 (55), 41 (94), 39 (54). After flash chromatography of 50 mg from this crude oil on silica with ether-pentane (2:1), fractions devoid of any trace of α:-nootkatol were pooled yielding 3.6 mg of β-nootkatol. 1H NMR (200 MHz, C6D6) δ 0.83 (d, 3H, J=3 Hz), δ 0.95 (s, 3H), δ 0.96–1.47 (m, 7H), δ 1.75 (m, 3H), δ 1.93 (dt, 1H, J=12.7 and 2.7 Hz), δ 2.07 (m, 1H), δ 2.20–2.33 (m, 2H), δ 4.19–4.26 (m, 1H), δ 4.88 (br s, 2H), 5.44 (br d, 1H). 13C NMR (100 MHz, DEPT, CDCl3) δ 15.7 (q), δ 18.4 (q), δ 21.1 (q), δ 32.8 (t), δ 33.4 (t), δ 37.8 (t), δ 38.5 (s), δ 39.8 (d), δ 41.3 (d), δ 45.1 (t), δ 68.1 (d), δ 109.2 (t), 125.9 (d), δ 144.9 (s), δ 150.2 (s). EIMS (70 eV) m/z: 220 [M]+ (56), 177 (100), 145 (31), 135 (51), 131 (43), 123 (38), 121 (91), 119 (81), 109 (42), 107 (66), 105 (62), 95 (49), 93 (69), 91 (87), 81 (39), 79 (60), 77 (56), 69 (45), 67 (51) 55 (62), 53 (42), (52), 41 (100), 39 (55).
Reaction SMILES: [C:1]([C:9]1[N:13]([CH3:14])[C:12]([CH:15]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)C(OCC)=O)=[CH:11][C:10]=1[CH3:30])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-]>CO.C1COCC1>[C:1]([C:9]1[N:13]([CH3:14])[C:12]([CH2:15][C:21]2[CH:22]=[CH:23][C:24]([N+:27]([O-:29])=[O:28])=[CH:25][CH:26]=2)=[CH:11][C:10]=1[CH3:30])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)C(c1ccc([N+](=O)[O-])cc1)c1cc(C)c(C(=O)c2ccccc2)n1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(Cc2ccc([N+](=O)[O-])cc2)n(C)c1C(=O)c1ccccc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 98.9 %

Procedure:
Ethyl 2-(5-benzoyl-1,4-dimethylpyrrol-2-yl)-2-(4-nitrophenyl)acetate (8.2 g, 20.2 mmol) [prepared by proceeding as described in Example 1, Steps (a) and (b)] was dissolved in a 1:1 mixture of methanol/THF (200 ml). An aqueous solution of LiOH (250 ml, 0.4M, 100.9 mmol) was added and the mixture was stirred at 60° C. for 2 h. The organic solvents were evaporated in vacuo, the aqueous residue was acidified with 10% HCl, and the product was extracted into ethyl acetate. The organic phase was washed with water, dried over sodium sulfate, and concentrated under vacuum. Purification on a Florisil® column (hexane-ethyl acetate, 4:1) gave 4-[5-benzoyl-1,4-dimethyl-1H-pyrrol-2-ylmethyl]-nitrobenzene (6.68 g, 99%) as a yellow solid. ##STR23##
Reaction SMILES: I[C:2]1[CH:18]=[CH:17][C:5]([C:6]([O:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[O:7])=[CH:4][CH:3]=1.Br[C:20]1[C:24]2[O:25][C:26]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[CH:27][C:28](=[O:29])[C:23]=2[S:22][CH:21]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].COCCOC>[O:33]1[CH2:34][CH2:35][N:30]([C:26]2[O:25][C:24]3[C:20]([C:2]4[CH:18]=[CH:17][C:5]([C:6]([O:8][CH2:9][CH2:10][N:11]5[CH2:16][CH2:15][O:14][CH2:13][CH2:12]5)=[O:7])=[CH:4][CH:3]=4)=[CH:21][S:22][C:23]=3[C:28](=[O:29])[CH:27]=2)[CH2:31][CH2:32]1
Reactant: O=c1cc(N2CCOCC2)oc2c(Br)csc12
Reactant: O=C(OCCN1CCOCC1)c1ccc(I)cc1
Agent: Cl[Pd]Cl
Agent: [Fe]
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Solvent: COCCOC
Solvent: ClCCl
Product: O=C(OCCN1CCOCC1)c1ccc(-c2csc3c(=O)cc(N4CCOCC4)oc23)cc1
Temperature: 140 °C

Procedure:
A 2 mL microwave vial was charged with a magnetic stirring bar, 2-morpholinoethyl 4-iodobenzoate (90 mg, 249 μmol), 3-bromo-5-morpholino-7H-thieno[3,2-b]pyran-7-one (103) (79 mg, 249 μmol), bis(pinacolato)diboron (70 mg, 274 gmol), cesium carbonate (325 mg, 997 dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (6 mg, 7 μmol), and 1,2-dimethoxyethane (1 mL). The reaction mixture was sealed, and the reaction mixture was magnetically stirred and heated under microwave irradiation to 140° C. for 15 minutes to give 2-morpholinoethyl 4-(5-morpholino-7-oxo-7H-thieno[3,2-b]pyran-3-yl)benzoate (77).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH:13]=[CH:14][CH:15]=2)[C:10]([C:28](=[O:34])[C:29]([O:31]CC)=[O:30])=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+]>C1COCC1.O>[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:25])[F:26])=[CH:19][CH:18]=3)[CH:13]=[CH:14][CH:15]=2)[C:10]([C:28](=[O:34])[C:29]([OH:31])=[O:30])=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C(=O)c1cn(Cc2ccccc2)c2cccc(-c3ccc(OC(F)(F)F)cc3)c12
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C(=O)c1cn(Cc2ccccc2)c2cccc(-c3ccc(OC(F)(F)F)cc3)c12
Yield: 83.5 %

Procedure:
{1-Benzyl-4-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic acid was prepared from ethyl {1-benzyl-4-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetate (0.167 g, 0.357 mmol), and potassium hydroxide. (0.103 g, 1.84 mmol) in THF (5 mL) and water (5 mL), according to the procedure described in Step 4 of Example 5. Drying for 12 hours at 90° C. furnished the title compound as a light yellow solid (0.131 g, 83%), mp: 167-169° C. (dec.). Mass spectrum (+ESI, [M+H]+) m/z 440; 1HNMR (500 MHz, DMSO-d6): δ 13.5-14.0 (br s, 11H), 8.65 (s, 1H), 7.65 (d, 1H, J=8.2 Hz), 7.25-7.4 (m, 10H), 7.15 (d, 2H, J=7.3 Hz), and 5.6 ppm (s, 2H). Elemental Analysis for C24H16F3NO4: Calculated: C, 65.61; H, 3.67; N, 3.19. Found: C, 65.57; 3.50; N, 3.16.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:11]([O:10][C:8]1[CH:7]=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([OH:1])[CH:9]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=Cc1ccc(O)cc1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=Cc1ccc(OCc2ccccc2)cc1O
Temperature: 25 °C
Reaction time: 72 h

Procedure:
13.8 g (0.1 mol) 2,4-dihydroxybenzaldehyde are dissolved in 150 ml acetone, 17.1 g (0.1 mol) benzylbromide and 13.8 g (0.1 mol) potassium carbonate are added, and the mixture is stirred at room temperature for 3 d. After filtration, the solvent is removed in vacuo and the residual crude product further purified by column chromatography on silica gel using dichloromethane as eluent.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:6][CH:5]([OH:7])[C:4]([CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([CH2:8][CH3:9])[O:3]1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl>[CH3:19][C:2]1([CH3:1])[CH2:6][C:5](=[O:7])[C:4]([CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([CH2:8][CH3:9])[O:3]1
Reactant: CCC1(COCc2ccccc2)OC(C)(C)CC1O
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CCC1(COCc2ccccc2)OC(C)(C)CC1=O
Yield: 73.1 %

Procedure:
The compound of Example 26 (1.2 g), methylene chloride (10 ml) and pyridinium chlorochromate (1.08 g) were stirred together for 24 hours at ambient temperature. The resulting solution was filtered through a column of Fluorosil (Trade Mark) using methylene chloride as eluant. Evaporation of the solvent gave 0.87 g (73.7%) of the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7](O)[CH:6]=[N:5]2.[NH4+].[OH-].O=P(Cl)(Cl)[Cl:17]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:17])[CH:6]=[N:5]2
Reactant: Oc1cnc2cc(Br)ccc2n1
Reactant: O=P(Cl)(Cl)Cl
Agent: [NH4+]
Agent: [OH-]
Product: Clc1cnc2cc(Br)ccc2n1
Yield: 92 %

Procedure:
6-Bromo-2-quinoxalinol (631 mg) in POCl3 (6.3 mL) was refluxed for 2 h, then poured onto ice. The solution was neutralized to pH 7 by addition of NH4OH, and the resulting solid collected by filtration. Washing with water and drying in vacuo gave 6-bromo-2-chloroquinoxaline (627 mg, 92%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[N:17][S:18]([CH3:21])(=[O:20])=[O:19])OC2C=CC=CC=2)[CH:5]=[CH:6][CH:7]=1.[CH3:22][C:23]1[C:31]2[C:30]([N:32]3[CH2:37][CH2:36][NH:35][C@@H:34]([CH3:38])[CH2:33]3)=[N:29][CH:28]=[N:27][C:26]=2[NH:25][CH:24]=1.C(N(CC)CC)C>CC#N>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:35]2[CH2:36][CH2:37][N:32]([C:30]3[C:31]4[C:23]([CH3:22])=[CH:24][NH:25][C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:33][C@@H:34]2[CH3:38])=[N:17][S:18]([CH3:21])(=[O:19])=[O:20])[CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)N=C(Nc1cccc(Br)c1)Oc1ccccc1
Reactant: Cc1c[nH]c2ncnc(N3CCN[C@@H](C)C3)c12
Solvent: CCN(CC)CC
Solvent: CC#N
Product: Cc1c[nH]c2ncnc(N3CCN(C(=NS(C)(=O)=O)Nc4cccc(Br)c4)[C@@H](C)C3)c12

Procedure:
The carbamimidate from step B (100 mg, 0.27 mmol), (S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine, from Example 1, step B (63 mg, 0.27 mmol), and triethylamine (77 μl, 0.27 mmol) were combined in MeCN (1.5 ml) and heated to reflux for 2 hours. The mixture was concentrated and purified by preparative HPLC to afford (S)—N-(3-bromophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N′-(methylsulfonyl)piperazine-1-carboximidamide.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]#[N:12])=[CH:10][C:5]=2[NH:4][C:3]1=[O:13].[ClH:14]>CO.CCOC(C)=O.O.[Pd]>[ClH:14].[NH2:12][CH2:11][C:9]1[CH:8]=[CH:7][C:6]2[N:2]([CH3:1])[C:3](=[O:13])[NH:4][C:5]=2[CH:10]=1
Reactant: Cn1c(=O)[nH]c2cc(C#N)ccc21
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: Cn1c(=O)[nH]c2cc(CN)ccc21
Temperature: 25 °C
Reaction time: 50 h
Yield: 64 %

Procedure:
The suspension of 1-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-5-carbonitrile (1.84 g, 10.6 mmol) in MeOH (30 ml) and 38% HCl aqueous solution (5.0 ml) was treated with 10% Pd—C (500 mg) and the mixture was stirred for 50 hours at room temperature under hydrogen atmosphere (4.0 kgf/cm2). After the filtration to remove Pd—C, the filtrate was evaporated to give the crude residue, which was dissolved in EtOAc/38% HCl aqueous solution/water (30:1:30). After washing the aqueous phase with EtOAc, water was removed under reduced pressure, followed by recrystallization from DCM-MeOH to furnish the title compound as a dark pink colored solid (1.45 g, 64%). 1H NMR (CDCl3): δ 3.27 (3H, s), 3.99 (2H, m), 6.90 (3H, m), 8.42 (2H, brs), 11.1 (1H, s). MS (ESI) m/z 179 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.[Cl:9][CH2:10][C:11](Cl)=[O:12]>>[Cl:9][CH2:10][C:11]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1)=[O:12]
Reactant: Nc1ccc(Cl)cn1
Reactant: O=C(Cl)CCl
Product: O=C(CCl)Nc1ccc(Cl)cn1
Yield: 20 %

Procedure:
The sub-titled compound (0.33 g, 20%) was prepared by a similar procedure to that used to prepare Example 14f using 2-amino-5-chloropyridine in place of 2-amino-pyridine and adding the chloroacetyl chloride at room temperature rather than at 0° C.
Reaction SMILES: [CH2:1]([S:13][C:14]1[N:15]=[N:16][N:17]([CH:19]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([OH:22])=O)[N:18]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(C1N=NN(CC(O)=O)N=1)CCCCCCCCC.[CH3:48][O:49][C:50]1[CH:56]=[C:55]([O:57][CH3:58])[CH:54]=[C:53]([O:59][CH3:60])[C:51]=1[NH2:52].C(C1C=CC=C(C(C)C)C=1N)(C)C>>[CH2:1]([S:13][C:14]1[N:15]=[N:16][N:17]([CH:19]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([NH:52][C:51]2[C:53]([O:59][CH3:60])=[CH:54][C:55]([O:57][CH3:58])=[CH:56][C:50]=2[O:49][CH3:48])=[O:22])[N:18]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCSc1nnn(C(C(=O)O)c2ccccc2)n1
Reactant: COc1cc(OC)c(N)c(OC)c1
Agent: CC(C)c1cccc(C(C)C)c1N
Agent: CCCCCCCCCCc1nnn(CC(=O)O)n1
Product: CCCCCCCCCCCCSc1nnn(C(C(=O)Nc2c(OC)cc(OC)cc2OC)c2ccccc2)n1

Procedure:
When in the general procedure of Example 88 an appropriate amount of (±)-5-(dodecylthio)-α-phenyl-2H-tetrazole-2-acetic acid was substituted for 5-decyl-2H-tetrazole-2-acetic acid and 2,4,6-trimethoxyaniline was substituted for 2,6-diisopropylaniline, the title compound was obtained, mp 141°-143° C.
Reaction SMILES: [C:1]([O:4][CH:5]([CH3:9])[C:6](O)=[O:7])(=[O:3])[CH3:2].C(Cl)(=O)C([Cl:13])=O>>[C:1]([O:4][CH:5]([CH3:9])[C:6]([Cl:13])=[O:7])(=[O:3])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(=O)OC(C)C(=O)O
Product: CC(=O)OC(C)C(=O)Cl

Procedure:
Stir a mixture of 2-acetoxy-propionic acid (550 g, 4.16 mol) in oxalyl chloride (500 mL) at room temperature for overnight. After removal of oxalyl chloride under vacuum, ˜700 g crude product is obtained (quantitative yield crude), which is used directly in the next step. 1H NMR (CDCl3, 400 MHz): δ 5.16 (m, 1H), 2.13 (s, 3H), 1.58 (d, J=7.2, 3H).
Reaction SMILES: [C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([C:7]2([CH3:13])[CH2:11][C:10](=[O:12])[NH:9][NH:8]2)=[CH:3][CH:2]=1.[Br:20]Br>C(O)(=O)C>[Br:20][C:17]1[CH:16]=[CH:15][C:14]([C:1]2[CH:6]=[CH:5][C:4]([C:7]3([CH3:13])[CH2:11][C:10](=[O:12])[NH:9][NH:8]3)=[CH:3][CH:2]=2)=[CH:19][CH:18]=1
Reactant: CC1(c2ccc(-c3ccccc3)cc2)CC(=O)NN1
Reactant: BrBr
Solvent: CC(=O)O
Product: CC1(c2ccc(-c3ccc(Br)cc3)cc2)CC(=O)NN1

Procedure:
Analogously to b), 3-(4-biphenylyl)-3-methyl-pyrazolidin-5-one and the calculated theoretically required quantity of bromine in acetic acid give 3-(4'-bromo-4-biphenylyl)-3-methyl-pyrazolidin-5-one.
Reaction SMILES: [CH2:1]([P:10]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([CH2:12][CH2:13][P:14]([CH2:22][C:23]1[C:24]([O:29][CH3:30])=[CH:25][CH:26]=[CH:27][CH:28]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=O)=O)[C:2]1[C:3]([O:8][CH3:9])=[CH:4][CH:5]=[CH:6][CH:7]=1.Cl[SiH](Cl)Cl.C(N(CC)CC)C.C1C=CC=CC=1>CO.C(#N)C>[CH2:1]([P:10]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:12][CH2:13][P:14]([CH2:22][C:23]1[C:24]([O:29][CH3:30])=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:2]1[C:3]([O:8][CH3:9])=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccccc1CP(=O)(CCP(=O)(Cc1ccccc1OC)c1ccccc1)c1ccccc1
Agent: Cl[SiH](Cl)Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Solvent: CC#N
Product: COc1ccccc1CP(CCP(Cc1ccccc1OC)c1ccccc1)c1ccccc1

Procedure:
Reduction of 1,2-bis(o-anisylphenylphosphinyl) ethane was accomplished by refluxing 16.5 g. (0.12 mole) trichlorosilane and 12.2 g. (0.12 mole) triethylamine in 188 ml. of dry benzene for one hour. Then 3.0 g. (0.012 mole) of 1,2-bis(o-anisylphenylphosphinyl) ethane in 75 ml. of dry acetonitrile was added and the mixture refluxed 1.5 hours. Quenching in 30% sodium hydroxide solution followed by separating and evaporating the organic layer gave 1.4 g. of crude crystals which were insoluble in cold methanol. Further crystallization from hot methanol gave 1,2-bis(o-anisylphenylphosphino) ethane, m.p. 102°-104° C., [α]D20 - 83.4° (C = 0.5 in CHCl3). The mass spectra gave a very strong parent peak at 458 and the nmr confirmed the structure.
Reaction SMILES: [SH:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]=[C:7]([NH:9]C(NCCN3CCOCC3)=O)[S:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:30]1[N:34]2[N:35]=[C:36]([C:39]3[CH:40]=[N:41][N:42]([CH3:44])[CH:43]=3)[CH:37]=[CH:38][C:33]2=[N:32][N:31]=1.C(=O)([O-])O>O.CS(C)=O>[CH3:44][N:42]1[CH:43]=[C:39]([C:36]2[CH:37]=[CH:38][C:33]3[N:34]([C:30]([S:1][C:2]4[CH:22]=[CH:21][C:5]5[N:6]=[C:7]([NH2:9])[S:8][C:4]=5[CH:3]=4)=[N:31][N:32]=3)[N:35]=2)[CH:40]=[N:41]1
Reactant: Cn1cc(-c2ccc3nnc(Cl)n3n2)cn1
Reactant: O=C(NCCN1CCOCC1)Nc1nc2ccc(S)cc2s1
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: Cn1cc(-c2ccc3nnc(Sc4ccc5nc(N)sc5c4)n3n2)cn1
Temperature: 190 °C
Reaction time: 0.5 h
Yield: 38.1 %

Procedure:
280 mg of 1-(6-sulphanyl-benzothiazol-2-yl)-3-(2-morpholin-4-yl-ethyl)urea, 2 cm3 of dimethyl sulphoxide and 240 mg of potassium carbonate are introduced, at 20° C., in a microwave tube equipped with a magnetic stirrer. The suspension thus obtained is stirred for 5 minutes before the addition of 200 mg of 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazine. The reaction mixture is then heated in a microwave oven for 10 minutes at 190° C., and then poured into 100 cm3 of water. The resulting mixture is stirred for 30 minutes under cold conditions. The solid is filtered off, washed with 3×100 cm3 of water and then spin-filter-dried. The brown powder thus obtained is purified by chromatography on silica gel (eluent: 95/5/0.5 dichloromethane/methanol/aqueous ammonia). A small amount of methanol and of hydrochloric acid in solution in dioxane is added to the fractions containing the expected product (to improve solubility). The fractions are combined and concentrated under reduced pressure. The oil thus obtained is taken up with 20 cm3 of a saturated aqueous solution of hydrogen carbonate (pH 8-9). The precipitate formed is filtered off and then washed with 3×20 cm3 of water and dried under vacuum. 120 mg of 6-{[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-amine are thus obtained in the form of a light brown solid.
Reaction SMILES: Br[C:2]1[C:3](=[O:11])[C:4]([O:9][CH3:10])=[CH:5][C:6](=[O:8])[CH:7]=1.[Si](O[N:20]=[C:21]([CH3:24])[CH:22]=[CH2:23])(C(C)(C)C)(C)C>ClC1C=CC=CC=1>[CH3:10][O:9][C:4]1[C:3](=[O:11])[C:2]2[N:20]=[C:21]([CH3:24])[CH:22]=[CH:23][C:7]=2[C:6](=[O:8])[CH:5]=1
Reactant: C=CC(C)=NO[Si](C)(C)C(C)(C)C
Reactant: COC1=CC(=O)C=C(Br)C1=O
Solvent: Clc1ccccc1
Product: COC1=CC(=O)c2ccc(C)nc2C1=O
Yield: 56.8 %

Procedure:
In a 50 mL round bottom flask 2-bromo-6-methoxy-1,4-benzoquinone (282 mg, 1.3 mmol) was dissolved in dry chlorobenzene (28 mL) along with 1-(tert-butyldimethylsilyloxy)-2-methyl-1-aza-1,3-butadiene (130 mg, 0.65 mmol). The solution was stirred and heated to reflux for 22 h under N2. The dark reaction was allowed to cool and was added to a silica gel column (2.5×9 cm). The column was eluted with EtOAc/hexane (5:1) then EtOAc and finally ethanol. The solvent was removed, benzene was added, and the resulting mixture was heated and filtered to remove insoluble impurities. Evaporation of the filtrate gave 75 mg, 57% of the crude product. 1H NMR (CDCl3) δ2.81 (s, 3H), 3.92 (s, 3H), 6.18 (s, 1H), 7.44 (d, J=5 Hz, 1H) 8.80 (d, J=5 Hz, 1H).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13]Br)=[C:9]([CH2:15][CH3:16])[CH:8]=1>CN(C=O)C.O>[Br:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)=[C:9]([CH2:15][CH3:16])[CH:8]=1
Reactant: CCc1cc(Br)ccc1CBr
Reactant: c1cn[nH]c1
Solvent: CN(C)C=O
Solvent: O
Product: CCc1cc(Br)ccc1Cn1cccn1
Temperature: 80 °C
Reaction time: 13 h
Yield: 79.6 %

Procedure:
A solution of pyrazole (616 mg, 9.1 mmol) in anhydrous DMF (30 mL) was treated with naH (60%, 362 mg). 4-Bromo-1-bromomethyl-2-ethyl-benzene (2.5 g, 9.1 mmol) was added and the resulting solution was stirred at 80° C. for 13 hours before it was cooled down to room temperature. The mixture was diluted with H2O, extracted with Et2O. The combined organic extracts were washed with H2O, brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography to afford the desired product (1.92 g, 80% yield). 1H NMR (300 MHz, CDCl3): δ 1.15 (t, J=7.5 Hz, 3H), 2.59-2.66 (m, 2H), 5.30 (s, 2H), 6.26-6.28 (m, 1H), 6.86-6.88 (m, 1H), 7.29-7.32 (m, 2H), 7.37-7.38 (m, 1H), 7.54-7.55 (m, 1H).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[Cl:19][C:20]1[S:24][C:23]([S:25](Cl)(=[O:27])=[O:26])=[CH:22][CH:21]=1>>[Cl:19][C:20]1[S:24][C:23]([S:25]([NH:18][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[C:7]([F:8])[C:6]=2[NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])(=[O:27])=[O:26])=[CH:22][CH:21]=1
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Reactant: O=S(=O)(Cl)c1ccc(Cl)s1
Product: O=S(=O)(Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F)c1ccc(Cl)s1

Procedure:
According to the general procedure B, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene 1,2-diamine was reacted with 5-chlorothiophene-2-sulfonyl chloride to obtain the title compound. 1H NMR (300 MHz, CDCl3): δ 7.38 (dd, J=1.5 & 10.2 Hz, 1H), 7.32 (ddd, J=2.1, 5.1 & 9.3 Hz, 1H), 7.25 (d, J=3.9 Hz, 1H), 7.10 (dd, J=9.0 & 18.6 Hz, 3H), 6.84 (d, J=4.2 Hz, 1H), 5.86 (dt, J=1.8, 8.7 & 17.4 Hz, 1H), 5.49 (br s, D2O exchangeable, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@@H:12]3[CH:16]([OH:19])[CH:17]([OH:18])[C@@H:5]([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>C(O)(=O)C>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]([CH:16]=[O:19])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]([CH:17]=[O:18])[C:4]=2[CH:3]=1
Reactant: OC1C(O)[C@H]2c3ccccc3[C@@H]1c1ccc(Cl)cc12
Agent: CC(=O)[O-]
Agent: [Pb+4]
Solvent: CC(=O)O
Product: O=CC1c2ccccc2C(C=O)c2cc(Cl)ccc21
Reaction time: 0.17 h

Procedure:
To a solution of 2.7 g. of cis-2-chloro-9,10-dihydro-9,10-ethanoanthracene-11,12-diol in 20 ml. of acetic acid at room temperature is added 5.0 g. of lead tetraacetate (containing 10% acetic acid) portionwise. The mixture is stirred for 10 minutes, cooled in an ice-water bath and the crystals which form are collected by filtration and washed with cold acetic acid, giving the desired product as off-white crystals, m.p. 113°-115° C.