Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:22]4[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=4[Cl:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[N-:30]=[N+:31]=[N-:32].[Na+]>>[Cl:29][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([Cl:28])[C:22]=1[C:21]1[C:15]2[O:14][CH:13]([CH2:12][N:30]=[N+:31]=[N-:32])[CH2:17][C:16]=2[CH:18]=[CH:19][CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(-c4c(Cl)cccc4Cl)c3O2)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Product: [N-]=[N+]=NCC1Cc2cccc(-c3c(Cl)cccc3Cl)c2O1
Yield: 89.8 %

Procedure:
Treatment of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.75 g, 1.67 mmol) with sodium azide (0.43 g, 6.67 mmol) generally according to the procedure described for Intermediate 98 afforded 0.48 g (90%) of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl azide. Treatment of the azide with triphenylphosphine (0.393 g, 1.49 mmol) generally according to the procedure described for Example 21 afforded 0.348 g (71%) of (±)-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. mp 206-208° C.; Anal. calcd. for C15H13Cl2NOHCl: C, 54.49; H, 4.27; N, 4.24. Found: C, 54.38; H, 4.36; N, 4.12.
Reaction SMILES: [N:1]1([C:7]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:8]=2[C:9](Cl)=[O:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH:19]1[CH2:24][CH:23]=[C:22]([C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)[CH2:21][CH2:20]1>>[N:1]1([C:7]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:8]=2[C:9]([N:19]2[CH2:20][CH:21]=[C:22]([C:25]3[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=3)[CH2:23][CH2:24]2)=[O:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: N#Cc1ccc(C2=CCNCC2)cc1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1N1CCOCC1
Product: N#Cc1ccc(C2=CCN(C(=O)c3cc([N+](=O)[O-])ccc3N3CCOCC3)CC2)cc1

Procedure:
According to the procedure described for the synthesis of example 1, the title compound has been synthesized from 2-morpholin-4-yl-5-nitro-benzoyl chloride and 4-(1,2,3,6-Tetrahydro-pyridin-4-yl)-benzonitrile (CAS: 460365-22-4). MS (m/e): 417.0 (M−H, 100%)
Reaction SMILES: [NH3:1].[Si:2]([O:9][CH:10]([CH:23]=[CH2:24])[CH2:11][N:12]1[C:16]2[N:17]=[CH:18][N:19]=[C:20](Cl)[C:15]=2[C:14]([I:22])=[CH:13]1)([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3]>C1COCC1.O>[Si:2]([O:9][CH:10]([CH:23]=[CH2:24])[CH2:11][N:12]1[C:16]2[N:17]=[CH:18][N:19]=[C:20]([NH2:1])[C:15]=2[C:14]([I:22])=[CH:13]1)([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3]
Reactant: N
Reactant: C=CC(Cn1cc(I)c2c(Cl)ncnc21)O[Si](C)(C)C(C)(C)C
Solvent: O
Solvent: C1CCOC1
Product: C=CC(Cn1cc(I)c2c(N)ncnc21)O[Si](C)(C)C(C)(C)C
Temperature: 120 °C
Reaction time: 5 h

Procedure:
25% aqueous ammonia (9 ml) was added to a solution of 7-(2-(tert-butyldimethylsilyloxy)-3-butenyl)-4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (1.12 g) obtained in Step 3 in THF (7 ml). The mixture was stirred at 120° C. for 5 hours using a microwave reactor. The reaction mixture was cooled, and then diluted with water. The resulting precipitate was collected by filtration, washed with water, and then dried to obtain the title compound as a white solid (1.06 g).
Reaction SMILES: [CH2:1]([NH:3][NH2:4])[CH3:2].[F:5][C:6]([F:17])([F:16])[C:7](=O)[CH:8]([CH3:14])[C:9](OCC)=[O:10].Cl>C(O)C>[CH2:1]([N:3]1[C:9]([OH:10])=[C:8]([CH3:14])[C:7]([C:6]([F:17])([F:16])[F:5])=[N:4]1)[CH3:2]
Reactant: CCNN
Reactant: CCOC(=O)C(C)C(=O)C(F)(F)F
Agent: Cl
Solvent: CCO
Product: CCn1nc(C(F)(F)F)c(C)c1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.1 %

Procedure:
To a solution of 1.2 g (20.0 mmol) of ethylhydrazine in 20 ml of ethanol was added dropwise under stirring 4.4 g (20.0 mmol) of ethyl 4,4,4-trifluoro-2-methyl-3-oxobutanoate under ice-cooling so that the temperature in the reaction system did not exceed 10° C. After the dropwise addition, the whole was stirred at room temperature for 30 minutes. Then, 1 ml of concentrated hydrochloric acid was added into the reaction solution, followed by 2 days of stirring under refluxing. After the completion of the reaction was confirmed, the solvent was removed by evaporation under reduced pressure. Water was added to the residue, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and saline, successively, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure and the residue was washed with n-hexane to obtain 2.8 g (yield: 71.8%) of 1-ethyl-5-hydroxy-4-methyl-3-trifluoromethyl-1H-pyrazole as white crystals (melting point: 150 to 152° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[CH2:30])[CH2:10][CH2:11][O:12][Si:13]([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].N([CH:33]([C:38]([O:40][CH3:41])=[O:39])[C:34]([O:36][CH3:37])=[O:35])=N>>[CH3:37][O:36][C:34]([C:33]1([C:38]([O:40][CH3:41])=[O:39])[CH2:30][C:9]1([C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)[CH2:10][CH2:11][O:12][Si:13]([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:35]
Reactant: COC(=O)C(N=N)C(=O)OC
Reactant: C=C(CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)c1ccc(F)c(Cl)c1
Product: COC(=O)C1(C(=O)OC)CC1(CCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)c1ccc(F)c(Cl)c1

Procedure:
The title compound was prepared in 2.61 g yield starting from {[3-(3-chloro-4-fluorophenyl)-3-buten-1-yl]oxy}(1,1-dimethylethyl)diphenylsilane (P45, 3.624 g) and from dimethyl diazenylpropanedioate (1.98 g) according to a similar procedure described for Preparation 14.
Reaction SMILES: [Br:1][C:2]1[C:3]2[C:4]3[C:15]([CH2:16]Br)=[N:14][N:13]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:12](=[O:24])[C:5]=3[N:6]([CH3:11])[C:7]=2[CH:8]=[CH:9][CH:10]=1.[C-:25]#[N:26].[Na+].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[Br:1][C:2]1[C:3]2[C:4]3[C:15]([CH2:16][C:25]#[N:26])=[N:14][N:13]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:12](=[O:24])[C:5]=3[N:6]([CH3:11])[C:7]=2[CH:8]=[CH:9][CH:10]=1
Reactant: [C-]#N
Reactant: Cn1c2cccc(Br)c2c2c(CBr)nn(-c3ccccc3)c(=O)c21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: Cn1c2cccc(Br)c2c2c(CC#N)nn(-c3ccccc3)c(=O)c21
Yield: 99.3 %

Procedure:
A solution of 6.4 g (14.3 mmol) of 9-bromo-1-(bromomethyl)-5-methyl-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indol-4-one, of 3.6 g (73 mmol) of sodium cyanide and of 0.57 g (1 mmol) of tetrabutylammonium bromide in a mixture of 170 ml of dichloromethane and of 85 ml of water is heated at reflux for 3 h with mechanical stirring. Separation is carried out by settling and the reaction mixture is extracted with dichloromethane. The organic phase is washed with water and dried over sodium sulphate and the solvent is evaporated under reduced pressure. 5.6 g (14.2 mmol) of product are obtained, which product is used as is in the following stage.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3=[CH:14][CH2:15][CH2:16][CH2:17][C:12]3([CH2:18][C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[NH:11][C:10]2=[O:27])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:28](OC(=O)C)(=[O:30])[CH3:29]>>[C:28]([N:11]1[C:12]2([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=3)[CH2:17][CH2:16][CH2:15][CH:14]=[C:13]2[N:9]([C:4]2[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=2)[C:10]1=[O:27])(=[O:30])[CH3:29]
Reactant: CC(=O)OC(C)=O
Reactant: N#Cc1ccc(CC23CCCC=C2N(c2cc(Cl)cc(Cl)c2)C(=O)N3)cc1
Product: CC(=O)N1C(=O)N(c2cc(Cl)cc(Cl)c2)C2=CCCCC21Cc1ccc(C#N)cc1

Procedure:
4-[1-(3,5-Dichlorophenyl)-2-oxo-1,2,3,4,5,6-hexahydro-benzimidazol-3a-ylmethyl]benzonitrile (150 mg) (0.38 mmol) in acetic anhydride (5 ml) was refluxed 3 days. After cooling, the reaction mixture was poured on water and extracted with tBuOMe. The organic layer was washed with water, dried over Na2SO4 and concentrated. The residue was chromatographed over silica gel (DCM/acetone, 97.5/2.5), then HPLC to give 4-[3-Acetyl-1-(3,5-Dichlorophenyl)-2-oxo-1,2,3,4,5,6-hexahydro-benzimidazol-3a-ylmethyl]benzonitrile (13.5 mg) as a white solid. 1H NMR (CDCl3): 7.55 (2H, d), 7.3-7.2 (3H, m), 6.70 (2H, m), 4.95 (1H, m), 3.70 (1H, d), 3.05 (1H, m), 2.50 (3H, s), 2.45-2.1 (2H, m), 2.1-1.6 (3H, m).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1.C(=O)([O-])O.[Na+].Br[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]#[N:29]>O>[CH3:1][N:2]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]#[N:29])[C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:7][CH:8]=1
Reactant: N#Cc1ccccc1CBr
Reactant: CCOC(=O)Cc1ccc(NC)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: CCOC(=O)Cc1ccc(N(C)Cc2ccccc2C#N)cc1
Yield: 112.8 %

Procedure:
N-Methyl-4-ethoxycarbonylmethylaniline (10 g), sodium hydrogencarbonate (5 g), water (5 ml), and 2-bromomethylcyanobenzene (12.2 g) were treated in the same manner as described in Example 1 for the preparation of the starting material. 18 g of N-methyl-N-(2-cyanobenzyl)-4-ethoxycarbonylmethylaniline was obtained as a light-yellow oily material.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:23])=O>CN(C)C=O.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([Cl:23])=[O:19])=[CH:4][CH:3]=1
Reactant: O=C(O)CCCCCCCC=Cc1ccc(F)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)CCCCCCCC=Cc1ccc(F)cc1

Procedure:
A solution of 10-(4-fluoro-phenyl)-dec-9-enoic acid (230 mg, 0.87 mmol), oxalyl chloride (0.11 mL, 1.3 mmol), and N,N-dimethylformamide (one drop) in dichloromethane (3 mL) was stirred at room temperature for 2 hours, then volatile material was removed by distillation to afford 10-(4-fluoro-phenyl)-dec-9-enoyl chloride. This was redissolved in dichloromethane, then N,N-diisopropylethylamine (140 mg, 1.04 mmol) was added dropwise, followed by (R)-3-amino-4-dimethylamino-butyric acid benzyl ester dihydrochloride. The reaction mixture was stirred at room temperature for 16 h, then washed with water. The organic layer was evaporated and the residue purified by preparative HPLC to afford (R)-4-dimethylamino-3-[10-(4-fluoro-phenyl)-dec-9-enoylamino]-butyric acid benzyl ester (100 mg, 24%), m/e=483.4 ([M+H]+).
Reaction SMILES: O=[C:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH2:5][CH2:4][CH:3]1[CH2:11][CH:12]=O.[C:14]([NH:17][CH2:18][CH2:19][NH2:20])(=[O:16])[CH3:15].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1>[N:20]1([CH2:19][CH2:18][NH:17][C:14](=[O:16])[CH3:15])[C:2]2[C:3](=[CH:4][CH:5]=[C:6]3[S:7][CH:8]=[CH:9][C:10]3=2)[CH:11]=[CH:12]1
Reactant: CC(=O)NCCN
Reactant: O=CCC1CCc2sccc2C1=O
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: Cc1ccccc1
Product: CC(=O)NCCn1ccc2ccc3sccc3c21

Procedure:
A 4.20 g of sodium periodate was added gradually to a mixture of 1.80 g of 5-allyl-4-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene, 25 mg of osmium tetraoxide, 15 ml of water and 45 ml of dioxane, while keeping the reaction mixture at 24 to 26° C., and then the mixture was stirred at room temperature for 3 hours. After extraction of the reaction mixture with ethyl acetate, the organic layers were combined, washed with 2% sodium thiosulfate aqueous solution, water and brine in that order and then dried with anhydrous magnesium sulfate. After removal of the drying agent, the solvent was concentrated under a reduced pressure, and the resulting residue was purified by a silica gel column chromatography to give 1.33 g of (4-oxo-4,5,6,7-tetrahydrobenzo[b]thiophen-5-yl)acetaldehyde. A 1.32 g of the aldehyde compound and 1.39 g of N-acetylethylenediamine were dissolved in 50 ml of toluene. Then, 10 mg of camphorsulfonic acid was added, and the mixture was heated under reflux for 3 hours while removing the produced water. After cooling, the reaction solution was poured into ice-cooled saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate. The organic layers were combined, the drying agent was removed by filtration and then the solvent was concentrated under a reduced pressure to give 1.38 g of N-(2-(4,5-dihydro-1H-thieno[2,3-g]indol-1-yl)ethyl]acetaamide. From this compound, N-[2-(1H-thieno[2,3-g]indol-1-yl)ethyl]acetamide was obtained in the similar manner as described in Reference Example 60.
Reaction SMILES: [C:1]1([CH3:8])[C:2]([CH3:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.C(Cl)(Cl)Cl.[C:13]1(C)C=CC=C[CH:14]=1>>[CH2:7]1[C:2]2[C:1](=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:8][CH2:14][CH2:13]1
Reactant: Cc1ccccc1C
Reactant: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: c1ccc2c(c1)CCCC2

Procedure:
Compound I, II or III is then dissolved in toluene, xylene, tetralin, or chloroform to form a solution of concentration around 1-2 mol L−1. This solution may be inkjet printed to provide an effective organic semiconductor (OSC).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:11]=[CH:10][CH:9]=[C:6]([CH:7]=O)[C:5]=1[OH:12])[CH3:2].[CH3:13][O:14][C:15]1[CH:28]=[CH:27][C:18]([NH:19][S:20]([CH2:23][C:24](O)=[O:25])(=[O:22])=[O:21])=[CH:17][CH:16]=1>C(O)(=O)C>[CH2:1]([O:3][C:4]1[CH:11]=[CH:10][CH:9]=[C:6]2[C:5]=1[O:12][C:24](=[O:25])[C:23]([S:20]([NH:19][C:18]1[CH:27]=[CH:28][C:15]([O:14][CH3:13])=[CH:16][CH:17]=1)(=[O:22])=[O:21])=[CH:7]2)[CH3:2]
Reactant: COc1ccc(NS(=O)(=O)CC(=O)O)cc1
Reactant: CCOc1cccc(C=O)c1O
Solvent: CC(=O)O
Product: CCOc1cccc2cc(S(=O)(=O)Nc3ccc(OC)cc3)c(=O)oc12

Procedure:
A solution of 3-ethoxysalicylaldehyde (1 mmol) and 4-methoxyanilinosulfonyl acetic acid (1 mmol) in acetic acid (10 mL) was subjected to the General Procedure 1, Method A to yield the title compound; m.p. 196-198° C.
Reaction SMILES: Cl.[NH2:2][CH2:3][C@:4]([C:7]1[C:12]([F:13])=[C:11]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:10]=[C:9]([Br:21])[N:8]=1)([OH:6])[CH3:5].C([O-])(O)=O.[Na+].[N+:27]([C:30]1[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1)([O-:29])=[O:28]>C1COCC1.O>[Br:21][C:9]1[N:8]=[C:7]([C@@:4]([OH:6])([CH3:5])[CH2:3][NH:2][S:36]([C:33]2[CH:32]=[CH:31][C:30]([N+:27]([O-:29])=[O:28])=[CH:35][CH:34]=2)(=[O:37])=[O:38])[C:12]([F:13])=[C:11]([Si:14]([CH2:17][CH3:18])([CH2:19][CH3:20])[CH2:15][CH3:16])[CH:10]=1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Reactant: CC[Si](CC)(CC)c1cc(Br)nc([C@](C)(O)CN)c1F
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)c1cc(Br)nc([C@](C)(O)CNS(=O)(=O)c2ccc([N+](=O)[O-])cc2)c1F
Temperature: 2.5 °C
Reaction time: 8 h
Yield: 62.8 %

Procedure:
To a solution of crude (R)-1-amino-2-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-propan-2-ol hydrochloride (43.5 g, 109 mmol) in 335 ml THF was added a solution of NaHCO3 (21.02 g, 250 mmol) in 500 ml water. The mixture was cooled to 0-5° C. and a solution of 4-nitrobenzenesulfonyl chloride (26.5 g, 120 mmol) in 100 ml THF was added in a dropwise. The resulting emulsion was stirred overnight while allowing the temperature to reach rt. The mixture was extracted with TBME. The organic layer was dried with MgSO4.H2O, filtered and evaporated to give an orange resin which was purified on a silca gel column by eluting with Hexanes/10-20% EtOAc to yield 37.56 g of the title compound as a yellow resin. TLC (Hex/EtOAc 3/1) Rf=0.34; HPLC: RtH11=1.678 min; ESIMS: 548, 550 [(M+H)+, 1Br]; 1H-NMR (400 MHz, DMSO-d6): 8.40 (d, 2H), 8.06 (t, 1H), 7.97 (d, 2H), 7.45 (d, 1H), 5.42 (s, 1H), 3.23 (d, 2H), 1.44 (s, 3H) 0.97-0.81 (m, 15H); Chiral HPLC (Chiralpak AD-H 1213, UV 210 nm): 90% ee.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][CH2:6][CH:7]1[O:11][C:10](=[O:12])[N:9]([CH:13]([CH:18]([CH3:20])[CH3:19])[C:14](OC)=[O:15])[CH2:8]1.[BH4-].[Li+].O1CCCC1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][CH2:6][CH:7]1[O:11][C:10](=[O:12])[N:9]([CH:13]([CH:18]([CH3:19])[CH3:20])[CH2:14][OH:15])[CH2:8]1
Reactant: COC(=O)C(C(C)C)N1CC(COc2cccc(Cl)c2)OC1=O
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)C(CO)N1CC(COc2cccc(Cl)c2)OC1=O
Yield: 55 %

Procedure:
A procedure similar to that described in Preparation 5 was repeated, except that 0.93 g of methyl 2-[5-(3-chlorophenoxymethyl)-2-oxooxazolidin-3-yl]-3-methylbutanoate (polar isomer), obtained as described in Preparation 99, 118 mg of lithium borohydride, 10 ml of anhydrous tetrahydrofuran and 87 mg of anhydrous methanol were used, to give 0.47 g of the title compound having an Rf value of 0.48 (on silica gel thin layer chromatography, using a 2:1 by volume mixture of ethyl acetate and hexane as the developing solvent) from the polar diastereomer.
Reaction SMILES: ClC(Cl)(Cl)C[CH:4](Cl)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.S(=O)(=O)(O)O.Cl.[C:20]([OH:23])(=[O:22])[CH3:21]>>[C:20]([OH:23])(=[O:22])[CH:21]=[CH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: CC(=O)O
Reactant: ClC(CC(Cl)(Cl)Cl)c1ccccc1
Agent: Cl
Agent: O=S(=O)(O)O
Product: O=C(O)C=Cc1ccccc1
Reaction time: 5 h
Yield: 9.8 %

Procedure:
A mixture of 51.6 g of 1,1,1,3-tetrachloro-3-phenylpropane, 60 g of glacial acetic acid and 17.8 g of 55% sulphuric acid is refluxed under stirring at 115° to 122° C. for 5 h, after which time the evolution of hydrogen chloride ceases. The work-up of the reaction mixture as described in Example 1 yields 22.5 g and 2.9 g of cinnamic acid in 85.8% total yield (melting point 131.5° to 133° C., min. 99% purity).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].Br[C:19]([CH3:26])([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21]>CN(C=O)C>[CH2:23]([O:22][C:20](=[O:21])[C:19]([CH3:26])([N:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1)[CH3:25])[CH3:24]
Reactant: c1cncc(-c2c[nH]cn2)c1
Reactant: CCOC(=O)C(C)(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C)n1cnc(-c2cccnc2)c1
Reaction time: 1 h
Yield: 33 %

Procedure:
To a solution of 3-(1H-Imidazol-4-yl)-pyridine (1 eq) in DMF was added potassium carbonate (2 eq) under dry condition. After stirring for 1 hour, ethyl 2-bromoisobutyrate (5 eq) was added to the mixture. The solution was left stirring over 36 hours at room temperature. The reaction solvent was removed in vacuo and the solid was diluted with ethyl acetate washed with H2O, NaCl(sat), dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography using a solvent gradient of 97% DCM, 3% MeOH and 0.1% TEA to yield 2-Methyl-2-(4-pyridin-3-yl-imidazol-1-yl)-propionic acid ethyl ester (33%). MH+(260).
Reaction SMILES: [CH2:1]([O:3][P:4]([CH2:9][N:10]1[C:19]2[C:14](=[C:15]([N+:20]([O-])=O)[CH:16]=[CH:17][CH:18]=2)[C:13](=[O:23])[C:12]([CH3:24])=[CH:11]1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[ClH:25].[H][H]>CO.CCOCC.[Pd]>[ClH:25].[CH2:1]([O:3][P:4]([CH2:9][N:10]1[C:19]2[C:14](=[C:15]([NH2:20])[CH:16]=[CH:17][CH:18]=2)[C:13](=[O:23])[C:12]([CH3:24])=[CH:11]1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]
Reactant: CCOP(=O)(Cn1cc(C)c(=O)c2c([N+](=O)[O-])cccc21)OCC
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: CCOCC
Product: CCOP(=O)(Cn1cc(C)c(=O)c2c(N)cccc21)OCC
Yield: 99 %

Procedure:
A solution of (3-Methyl-5-nitro-4-oxo-4H-quinolin-1-ylmethyl)-phosphonic acid diethyl ester (Compound 303B, 20 mg; 0.05 mmol) in methanol (5 mL) was charged with Pd/C (5 mg) and 1M HCl in ether (1 mL) under nitrogen and stirred under 1 atmosphere of hydrogen overnight at RT. The solution was filtered the filtrate concentrated to get the final compound (yield 20 mg; 99%; tlc 1:9 MeOH:DCM); 1H NMR (300 MHz, CDCl3), δ ppm, 8.12 (s, 1H), 8.01 (d, 6 Hz, 1H,) 7.88-7.83 (m, 1H) 7.40 (d, J=9 Hz, 1H) 4.12-4.13 (m, 4H,) 3.31-3.29 (m, 2H), 2.14 (s, 3H), 1.27-1.25 (m, 6H)
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[C:16]([NH:18][CH:19]([CH3:21])[CH3:20])[C:5]([C:6]([NH:8][NH:9][C:10](=O)[C:11]([O:13][CH3:14])=[O:12])=O)=[CH:4][N:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:31])=CC=1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:6]2[S:31][C:10]([C:11]([O:13][CH3:14])=[O:12])=[N:9][N:8]=2)=[C:16]([NH:18][CH:19]([CH3:21])[CH3:20])[CH:17]=1
Reactant: COC(=O)C(=O)NNC(=O)c1cnc(Cl)cc1NC(C)C
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)c1nnc(-c2cnc(Cl)cc2NC(C)C)s1

Procedure:
To a stirred solution of methyl 2-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-2-oxoacetate (11) (1 g, 3.1 mmol) in THF (30 mL), Lawesson's reagent (6.3 mmol, 2 equiv) was added and heated to reflux for 3 h. The reaction mixture was diluted with EtOAc and washed twice with 10% NaHCO3 solution. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by column chromatography through silica gel and MeOH: DCM as eluent afford methyl 5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazole-2-carboxylate.
Reaction SMILES: S(O[CH:12]1[CH2:16][CH2:15][O:14][CH2:13]1)(C1C=CC(C)=CC=1)(=O)=O.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[C:39]3[C:38]([NH2:40])=[N:37][CH:36]=[N:35][C:34]=3[NH:33][CH:32]=2)=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[H-].[Na+]>CN(C)C=O>[CH2:17]([O:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]2[C:39]3[C:38]([NH2:40])=[N:37][CH:36]=[N:35][C:34]=3[N:33]([CH:12]3[CH2:16][CH2:15][O:14][CH2:13]3)[CH:32]=2)=[CH:29][CH:30]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Nc1ncnc2[nH]cc(-c3ccc(OCc4ccccc4)cc3)c12
Reactant: Cc1ccc(S(=O)(=O)OC2CCOC2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nc1ncnc2c1c(-c1ccc(OCc3ccccc3)cc1)cn2C1CCOC1

Procedure:
In a similar manner to Example 2, 3-tosyloxytetrahydrofuran (1.84 g) was reacted with 5-(4-benzyloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (2.9 g) using sodium hydride (0.30 g, of a 60% dispersion in mineral oil) and dimethylformamide (40 ml) except that the mixture was heated for 4.5 hours at 90° C. to give 5-(4-benzyloxyphenyl)-7-(3-tetrahydrofuryl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine as a solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([O-:13])=O)[S:10][C:3]=12.[Li+].S(Cl)(Cl)=O.[CH3:19][NH:20][CH2:21][CH2:22][OH:23].CCN(CC)CC>>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:20]([CH2:21][CH2:22][OH:23])[CH3:19])=[O:13])[S:10][C:3]=12
Reactant: CNCCO
Reactant: O=C([O-])c1cc2nccc(Cl)c2s1
Agent: [Li+]
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Product: CN(CCO)C(=O)c1cc2nccc(Cl)c2s1
Yield: 49.2 %

Procedure:
This material was prepared from lithium 7-chlorothieno[3,2-b]pyridine-2-carboxylate (1.0 g, 4.68 mmole) by treatment with thionyl chloride followed by reaction of the resultant acyl chloride with 2-(methylamino)ethanol (0.414 ml, 5.15 mmole) and Et3N (0.718 ml, 5.15 mmole), in a manner as previously described for example 9d to give a pale brown solid (0.624 g, 49% yield). 1H NMR (400 MHz, CDCl3) δ8.61 (1H, d, J=4.8 Hz), 7.80 (1H, s), 7.33 (1H, d, J=4.8 Hz), 3.92 (2H, m), 3.76 (2H, t, J=5.1 Hz), 3.37 (3H, s), 3.19 (1H, s); ESIMS (MH+): 259.10.