Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [P:1]([O:13][CH2:14][C@H:15]1[O:19][C@@H:18]([N:20]2[C:29]3[N:28]=[CH:27][N:26]=[C:24]([NH2:25])[C:23]=3[N:22]=[CH:21]2)[C@H:17]([OH:30])[C@@H:16]1[NH2:31])([O:4][P:5]([O:8][P:9]([OH:12])([OH:11])=[O:10])([OH:7])=[O:6])(=[O:3])[OH:2].C(=O)([O-])[O-].[K+].[K+].[C:38](ON1C(=O)CC(S(O)(=O)=O)C1=O)(=[O:40])[CH3:39].[Na]>O.CS(C)=O>[P:1]([O:13][CH2:14][C@H:15]1[O:19][C@@H:18]([N:20]2[C:29]3[N:28]=[CH:27][N:26]=[C:24]([NH2:25])[C:23]=3[N:22]=[CH:21]2)[C@H:17]([OH:30])[C@@H:16]1[NH:31][C:38](=[O:40])[CH3:39])([O:4][P:5]([O:8][P:9]([OH:11])([OH:12])=[O:10])([OH:7])=[O:6])(=[O:2])[OH:3]
Reactant: Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](N)[C@H]1O
Reactant: CC(=O)ON1C(=O)CC(S(=O)(=O)O)C1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na]
Solvent: CS(C)=O
Solvent: O
Product: CC(=O)N[C@H]1[C@@H](O)[C@H](n2cnc3c(N)ncnc32)O[C@@H]1COP(=O)(O)OP(=O)(O)OP(=O)(O)O
Yield: 11.9 %

Procedure:
3'-Amino-3'-deoxyadenosine 5'-triphosphate (15 mg, 26 mmol) and potassium carbonate (21 mg, 0.13 mmol) were dissolved in 2 ml of water. Sodium sulfosuccinimidyl acetate (36 mg, 0.13 mmol; Pierce Chemical, Rockford, Ill.) in 0.2 ml of dimethylsulfoxide (DMSO) was added at 0° C., and the reaction was allowed to proceed at room temperature for twenty-four hours. The product was purified by repeated injections on HPLC using a Synchropak RP-100 column (1×25 cm) applying a linear gradient of acetonitrile 5-22% TEAA (0.85 %/min, flow rate 3 ml/min, t=8.5 min). The appropriate fractions were collected and lyophilized to dryness. The product was obtained as a triethylammonium salt (8.5 mg, 39 %). UV: lmax =259 nm. High resolution MS for C12H18N6O13P3 : calcd. 547. 0145, found 547.0170 (MH3-).
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7](O)=[O:8])(=[O:3])[CH3:2].S(Cl)([Cl:19])=O>C1(C)C=CC=CC=1>[C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7]([Cl:19])=[O:8])(=[O:3])[CH3:2]
Reactant: CC(=O)SCC(Cc1ccccc1)C(=O)O
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CC(=O)SCC(Cc1ccccc1)C(=O)Cl
Reaction time: 10 h

Procedure:
Dissolve 10 g (42 mmole) of 2-acetylthiomethyl-3-phenyl propionic acid and 10 g (84 mmole) of thionyl chloride in 50 ml of toluene. Stir for 10 hrs. under nitrogen and concentrate in vacuo. Dissolve the residue in 50 ml of toluene and again concentrate in vacuo. Repeat this step five times to obtain the product as a light brown oil.
Reaction SMILES: [ClH:1].C(N(CC)CC)C.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)Cl.[C:23]([O:27][C:28](=[O:44])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]2[CH:42]=[C:41](O)[N:40]=[CH:39][N:38]=2)=[CH:32][CH:31]=1)([CH3:26])([CH3:25])[CH3:24]>CC#N>[C:23]([O:27][C:28](=[O:44])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]2[CH:42]=[C:41]([Cl:1])[N:40]=[CH:39][N:38]=2)=[CH:32][CH:31]=1)([CH3:26])([CH3:25])[CH3:24]
Reactant: Cl
Reactant: CC(C)(C)OC(=O)Nc1ccc(Cc2cc(O)ncn2)cc1
Solvent: CN(C)c1ccccc1
Solvent: CCN(CC)CC
Solvent: O=P(Cl)(Cl)Cl
Product: CC(C)(C)OC(=O)Nc1ccc(Cc2cc(Cl)ncn2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Triethylamine hydrochloride (0.93 g 6.60 mmol), N,N-dimethylaniline (0.8 mL, 6.60 mmol), and POCl3 (3.7 mL, 39.6 mmol, 6 equiv) are added sequentially to a solution of [4-(6-hydroxy-pyrimidin-4-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (2.0 g, 6.60 mmol) in CH3CN (16.5 mL), at rt and under an argon atmosphere. The resulting yellow solution is stirred at rt for 1 h and then added to a stirred mixture of H2O/ice (1/1, v/v; 80 mL, total volume). The product is extracted in CH2Cl2 (2×200 mL). The organic phase is washed with an aqueous saturated solution of Na2CO3 (70 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel (170 g) column chromatography (CH2Cl2/Et2O, 95/5, then 90/10) to afford the title compound: ES-MS: 320.1 [M+H]+; single peak at tR=8.76 min (System 2); Rf=0.13 (CH2Cl2/Et2O, 95/5).
Reaction SMILES: C([N:8]1[CH2:16][CH2:15][CH:11]([C:12](O)=[O:13])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.[C:17](N1C=CN=C1)([N:19]1C=CN=C1)=O.[ClH:29].CN.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[ClH:29].[CH3:17][NH:19][C:12]([CH:11]1[CH2:15][CH2:16][NH:8][CH2:9][CH2:10]1)=[O:13]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CN
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CNC(=O)C1CCNCC1
Reaction time: 8 h

Procedure:
To a stirring solution of BOC-isonipecotic acid (400 mg) in N,N-dimethylformamide (4 mL) was added 1,1′-carbonyldiimidazole (560 mg). The reaction mixture was stirred overnight and then methylamine hydrochloride (280 mg) and triethylamine (0.48 mL) were added. After 5 hours the reaction mixture was diluted with ethyl acetate, washed with water, dried (MgSO4) and the solvent removed in vacuo. Treatment with HCl yielded piperidine-4-carboxylic acid methylamide, which was isolated as the hydrochloride salt.
Reaction SMILES: [N:1]([C@H:4]1[CH2:9][C@H:8]([OH:10])[C@@H:7]([CH2:11][OH:12])[O:6][CH2:5]1)=[N+:2]=[N-:3].[CH3:13][O:14][C:15]1[CH:36]=[CH:35][C:18]([C:19](Cl)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[CH:17][CH:16]=1>N1C=CC=CC=1>[CH3:27][O:26][C:23]1[CH:22]=[CH:21][C:20]([C:19]([O:12][CH2:11][C@H:7]2[O:6][CH2:5][C@@H:4]([N:1]=[N+:2]=[N-:3])[CH2:9][C@@H:8]2[OH:10])([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:18]2[CH:35]=[CH:36][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)=[CH:25][CH:24]=1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: [N-]=[N+]=N[C@@H]1CO[C@H](CO)[C@@H](O)C1
Solvent: c1ccncc1
Product: COc1ccc(C(OC[C@H]2OC[C@@H](N=[N+]=[N-])C[C@@H]2O)(c2ccccc2)c2ccc(OC)cc2)cc1
Yield: 75.5 %

Procedure:
7.6 g (44 mmole) of 1,5-anhydro-2-azido-2,3-dideoxy-D-mannitol (4) were coevaporated with 3×40 ml of pyridine and then dissolved in 120 ml of pyridine. Thereafter, 19.6 g (53.3 mmole) of 4,4′-dimethoxytritylchloride in 120 ml of pyridine are added at r.t. within 1 h under stirring. The reaction mixture was stirred for another 2 h at r.t. Then pyridine was evaporated and the residue was dissolved in 800 ml of ethyl acetate und washed twice with 400 ml of 5% sodium hydrogencarbonate solution. Organic layer was separated, dried over sodium sulfate, filtered and evaporated to dryness. The residue was dissolved in 30 ml of ethyl acetate and purified by flash-chromatography over silica gel (n-hexane/ethyl acetate/1% triethylamine gradient). Product fractions were combined, evaporated and dried at high vacuum to yield 15.8 g (77%) of a yellowish foam.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26]Br>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:26][C:25]2[CH:28]=[CH:29][CH:30]=[C:23]([F:22])[CH:24]=2)[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Fc1cccc(CBr)c1
Reactant: O=c1cc(OCc2ccccc2)cc[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=c1cc(OCc2ccccc2)ccn1Cc1cccc(F)c1
Temperature: 110 °C
Yield: 67.2 %

Procedure:
To a solution of 4-benzyloxy-1H-pyridin-2-one (1.0 g, 5 mmol) and K2CO3 (2.0 g, 9.9 mmol) in DMF (30 mL) was added 3-fluorobenzyl bromide (1.4 g, 7.5 mmol), and the reaction mixture was heated to 110° C. for 3 h. The reaction mixture was cooled to room temperature, and partitioned between EtOAc and water. The organic solution was washed with water and then brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 97:3 to 93:7 methylene chloride/methanol) afforded 4-benzyloxy-1-(3-fluorobenzyl)-1H-pyridin-2-one (1.04 g, 67%): 1H NMR (300 MHz, CDCl3) δ 7.45-7.25 (m, 5H), 7.13 (d, J=8 Hz, 1H), 7.10-6.90 (m, 3H), 6.10-5.95 (m, 2H), 5.07 (s, 2H), 5.00 (s, 2H).
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]1([C:17]2[CH:18]=[N:19][N:20]3[CH:25]=[C:24]([C:26]4[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][CH2:34][OH:35])=[CH:28][CH:27]=4)[CH:23]=[N:22][C:21]=23)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C>ClCCl>[C:11]1([C:17]2[CH:18]=[N:19][N:20]3[CH:25]=[C:24]([C:26]4[CH:27]=[CH:28][C:29]([CH2:32][CH2:33][CH:34]=[O:35])=[CH:30][CH:31]=4)[CH:23]=[N:22][C:21]=23)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: OCCCc1ccc(-c2cnc3c(-c4ccccc4)cnn3c2)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=CCCc1ccc(-c2cnc3c(-c4ccccc4)cnn3c2)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
Dimethylsulfoxide (0.862 mL, 12.2 mmol, 5.00 equiv) was added to a solution of oxalyl chloride (0.636 mL, 7.29 mmol, 3.00 equiv) in dichloromethane (10 mL) at −78° C. The mixture was stirred for 15 minutes before a solution of 3-[4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]propan-1-ol (2-4, 0.800 g, 2.43 mmol, 1 equiv) in dichloromethane (100 mL) was added via cannula over 5 minutes. The resulting mixture was stirred at −78° C. for 1 hour. Triethylamine (3.50 mL, 25.1 mmol, 10.3 equiv) was added, and the mixture was then warmed to 0° C. and stirred for 30 minutes. The reaction mixture was partitioned between saturated sodium bicarbonate solution (100 mL) and additional dichloromethane (100 mL). The organic layer was dried over sodium sulfate and concentrated to give 3-[4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]propanal (2-5) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ9.86 (t, 1H, J=1.2 Hz), 8.82 (d, 1H, J=2.4 Hz), 8.81 (d, 1H, J=2.4 Hz), 8.46 (s, 1H), 8.06 (br d, 2H, J=7.8 Hz), 7.54 (d, 2H, J=8.2 Hz), 7.47 (t, 2H, J=7.8 Hz), 7.37 (d, 2H, J=8.2 Hz), 7.29 (t, 1H, J=7.8 Hz), 3.05 (t, 2H, J=7.1 Hz), 2.86 (t, 2H, J=7.1 Hz).
Reaction SMILES: [C-:1]#[N:2].[K+].[S:4]1[CH:8]=[CH:7][C:6]([CH:9]=[O:10])=[CH:5]1.C(O)(=O)C.C([O-])(O)=O.[Na+]>CO>[OH:10][CH:9]([C:6]1[CH:7]=[CH:8][S:4][CH:5]=1)[C:1]#[N:2]
Reactant: [C-]#N
Reactant: O=Cc1ccsc1
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: N#CC(O)c1ccsc1
Temperature: 15 °C
Reaction time: 0.5 h

Procedure:
To a stirred suspension of KCN (18.6 g, 286 mmol) in methanol (100 mL) was added thiophene-3-carbaldehyde (20 mL, 178 mmol) at 0° C. under nitrogen atmosphere. Then acetic acid (4.4 mL) was added dropwise at 0° C. After 30 minutes, the mixture was warmed to 15° C. and stirred for 20 hours. NaHCO3 (15 g) was added. The mixture was concentrated and extracted with ethyl acetate (200 mL). The organic mixture was washed with water (3×25 mL), brine (25 mL), dried over anhydrous sodium sulfate and concentrated to dryness. The residue was purified by column chromatography (ethyl acetate:petroleum ether, 1:10) to afford hydroxy-thiophen-3-yl-acetonitrile. (Yield 15 g, 60%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.F[C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][N:11]([C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1
Reactant: N#Cc1ccc(F)cc1
Reactant: FC(F)(F)C1(c2cc(Cl)cc(Cl)c2)CCNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: N#Cc1ccc(N2CCC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1
Temperature: 120 °C
Reaction time: 6 h
Yield: 13.1 %

Procedure:
To the solution of 3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.30 g) and 4-fluorobenzonitrile (0.12 g) in DMSO (dimethylsurufoxide) was added potassium carbonate (0.27 g), and the mixture was heated with stirring at 120° C. for 6 hours. The mixture was cooled to room temperature and then poured onto water, which was then extracted twice with ethyl acetate. The organic layer was combined, which was then washed with water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield 4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]benzonitrile (0.05 g). 1H-NMR (CDCl3) δ: 2.51-2.62 (1H, m), 2.86-2.94 (1H, m), 3.56-3.61 (2H, m), 3.80 (1H, d), 4.12 (1H, d), 6.59 (2H, d), 7.26 (2H, br s), 7.41 (1H, t), 7.52 (2H, d).
Reaction SMILES: [S:1]1[CH:5]=[C:4]([CH:6]=[O:7])[C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]1=2.[Li+].[Cl-].II.I[C:17]1S[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[C:18]=1C=O.C1(C#C)C=CC=CC=1>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CCN(CC)CC>[C:19]1([C:18]#[C:17][C:5]2[S:1][C:2]3[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=3[C:4]=2[CH:6]=[O:7])[CH:25]=[CH:24][CH:23]=[CH:22][CH:20]=1
Reactant: O=Cc1csc2ccccc12
Reactant: O=Cc1c(I)sc2ccccc12
Agent: [Pd]
Agent: II
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1CCOC1
Solvent: C#Cc1ccccc1
Solvent: CCN(CC)CC
Product: O=Cc1c(C#Cc2ccccc2)sc2ccccc12
Reaction time: 0.5 h
Yield: 63 %

Procedure:
Benzo[b]thiophene-3-carbaldehyde (27) (162 mg, 1.0 mmol) in THF (2 mL) was added to a solution of TMPZnCl.LiCl (2) (1.3 M in THF, 0.85 mL, 1.1 mmol) at 25° C. and the reaction mixture was then stirred at this temperature for 30 min according to TP 2. I2 (381 mg, 1.5 mmol) dissolved in dry THF (2 mL) was then dropwise added and the resulting mixture was stirred for 0.5 h. To the solution of freshly generated in situ 2-iodobenzo[b]thiophene-3-carbaldehyde, NEt3 (7 mL), Cul (8 mg, 4 mol %), Pd(dba)2 (17 mg, 3 mol %) and P(o-furyl)3 (14 mg, 6 mol %) in THF (2 mL) and phenylacetylene (254 mg, 1.5 mol, 1.5 equiv) were successively slowly added. The reaction mixture was stirred at rt for 2 h. The reaction mixture was quenched with a sat. aq. Na2S2O3 solution (10 mL) and with a sat. aq. NH4Cl solution (20 mL), extracted with diethyl ether (3×50 mL) and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash-chromatography (CH2Cl2/n-pentane, 1:2) furnished compound 29c (165 mg, 63%) as a yellowish solid.
Reaction SMILES: [Cl:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)=[O:4].C(N(CC)CC)C.C(O)=O.Cl>C1(C)C=CC(S(N[C@H](C2C=CC=CC=2)[C@@H](C2C=CC=CC=2)N)(=O)=O)=CC=1.Cl[Rh+]C1(C)C(C)=C(C)C(C)=C1C.C(OCC)(=O)C>[Cl:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)[OH:4]
Reactant: O=C(CCl)c1cccc(Cl)c1
Agent: CC1=C(C)C(C)([Rh+]Cl)C(C)=C1C
Agent: Cc1ccc(S(=O)(=O)N[C@H](c2ccccc2)[C@H](N)c2ccccc2)cc1
Agent: Cl
Solvent: O=CO
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: OC(CCl)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.3 %

Procedure:
2-Chloro-3′-chloroacetophenone (945.0 mg, 5.0 mmol), triethylamine (0.73 ml, 5.25 mmol), and formic acid (0.23 ml, 5.25 mmol) were added to an ethyl acetate (5.0 ml) solution containing chloro(pentamethylcyclopentadienyl)rhodium (III) (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (1.35 mg, 0.002 mmol, s/c=5000) which was prepared in the same manner as described in Organic Letters, 1999, vol. 1, pp. 841-843, Supporting Information (see the above-described URL), and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, 1 M hydrochloric acid (5.3 ml) was added, and the reaction product was extracted with ethyl acetate (5 ml) and dried over magnesium sulfate. Evaporation of the solvent yielded a desired compound, (+)-2-chloro-1-(3′-chlorophenyl)ethanol (891.5 mg; yield: 93.4%; optical purity: 93.8% ee).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]([CH3:16])[CH2:11][C:12]([F:15])([F:14])[F:13])=[CH2:9])=[CH:4][CH:3]=1.[OH-:17].[Na+].OO.[Cl-].[Na+]>C1COCC1.O>[F:15][C:12]([F:14])([F:13])[CH2:11][CH:10]([CH3:16])[CH:8]([C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)[CH2:9][OH:17]
Reactant: C=C(c1ccc(C)cc1)C(C)CC(F)(F)F
Reactant: [OH-]
Agent: OO
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(C(CO)C(C)CC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Under argon, 9.4 g (41.2 mmol) of 1-methyl-4-(5,5,5-trifluoro-3-methylpent-1-en-2-yl)benzene were dissolved in 130 ml of THF, 57.6 ml of a 1 M borane/THF complex solution were added and the mixture was stirred at room temperature for 24 h. With vigorous stirring, initially 79 ml of water, then 24 ml of 6 M aqueous sodium hydroxide solution and finally 14.5 ml (475 mmol) of 30% strength aqueous hydrogen peroxide solution were added. Subsequently, the reaction solution was added to 200 ml of saturated sodium chloride solution, the organic phase was separated off and the aqueous phase was extracted three more times with diethyl ether. The combined organic phases were dried over magnesium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1→2:1). This gave 5 g (20.3 mmol, 49% of theory) of the title compound as a colorless oil.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[OH-].[Zn+2:22].[OH-]>C(O)C>[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Zn+2:22].[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: [OH-]
Agent: [Zn+2]
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCC(=O)[O-]
Temperature: 20 °C

Procedure:
1,145 parts of stearic acid is added to 5,000 parts of ethanol, and the mixture is mixed at 75° C. 200 parts of zinc hydroxide is added thereto in small amounts, and the mixture is mixed for one hour from the point of completion of introduction. After the mixing, the mixture is cooled to 20° C., and the product is separated by filtration to remove ethanol and reaction residues. The solid product taken therefrom is dried for 3 hours at 150° C. using a heating type vacuum dryer. The product is removed from the dryer and is cooled naturally. Thus, solid zinc stearate is obtained.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=2)[C:5]([F:16])=[CH:4][N:3]=1.[CH2:17]([NH:20][C:21]([C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=1)[NH2:26])=[O:22])[CH2:18][CH3:19]>>[F:16][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=2)=[N:7][C:2]([NH:26][C:25]2[CH:27]=[CH:28][CH:29]=[C:23]([C:21]([NH:20][CH2:17][CH2:18][CH3:19])=[O:22])[CH:24]=2)=[N:3][CH:4]=1
Reactant: Oc1cccc(Nc2nc(Cl)ncc2F)c1
Reactant: CCCNC(=O)c1cccc(N)c1
Product: CCCNC(=O)c1cccc(Nc2ncc(F)c(Nc3cccc(O)c3)n2)c1

Procedure:
In like manner to the preparation of 5-fluoro-N4-(3-hydroxyphenyl)-N2-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)methyleneoxyphenyl]-2,4-pyrimidinediamine, 2-chloro-5-fluoro-N4-(3-hydroxyphenyl)-4-pyrimidineamine and 3-[(N-propylamino)carbonyl]aniline were reacted to provide 5-fluoro-N4-(3-hydroxyphenyl)-N2-[3-[(N-propylamino)carbonyl]phenyl]-2,4-pyrimidinediamine. 1H NMR (CD3OD): δ 8.00 (d, 1H, J=5.4 Hz), 7.84 (t, 1H, J=1.8 Hz), 7.69-7.59 (m, 2H), 7.44 (t, 1H, J=7.5 Hz), 7.16-7.05 (m, 3H), 6.67 (td, 1H, J=2.4 and 7.2 Hz), 3.34-3.29 (m, 2H), 1.65-1.56 (m, 2H), 0.96 (t, 3H, J=7.5 Hz); 19F NMR (282 MHz, CD3OD): −46049; LCMS: purity: 94%; MS (m/e): 382 (MH+).
Reaction SMILES: [Na].[CH:2]([C:4]1[CH:5]=[CH:6][C:7](C)=[C:8](S(O)(=O)=O)[CH:9]=1)=[O:3].CC1C=CC([CH:20]=[O:21])=CC=1.OS(O)(=O)=O.O=S(=O)=O>>[CH3:20][O:21][C:7]1[CH:6]=[CH:5][C:4]([CH:2]=[O:3])=[CH:9][CH:8]=1
Reactant: Cc1ccc(C=O)cc1
Reactant: Cc1ccc(C=O)cc1S(=O)(=O)O
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Agent: [Na]
Product: COc1ccc(C=O)cc1

Procedure:
The sodium salt of 5-formyl-2-methylbenzenesulphonic acid used as starting material for the bis-stilbene compound of the formula (88) is obtained by sulphonating 4-methylbenzaldehyde with oleum containing 66% of SO3 and purification via the barium salt. In a similar manner the sodium salt of 5-formyl-2methoxybenzenesulphonic acid, used as starting material for the bis-stilbene compound of the formula (89), is obtained from 4-methoxybenzaldehyde. ##SPC61##
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl:35][C:36]1[CH:37]=[C:38](O)[CH:39]=[CH:40][CH:41]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:35][C:36]1[CH:41]=[C:40]([CH:39]=[CH:38][CH:37]=1)[O:1][CH2:2][C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Oc1cccc(Cl)c1
Reactant: CN1C(=O)C[C@H](c2ccccc2)[C@@H]1CO
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN1C(=O)C[C@H](c2ccccc2)[C@@H]1COc1cccc(Cl)c1
Reaction time: 8 h
Yield: 23 %

Procedure:
To a solution of (±)-(4R*,5R*)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one (Intermediate T prepared by Method 2, 220 mg, 1.1 mmol), PPh3 (422 mg, 1.6 mmol) and 3-chlorophenol (0.13 mL, 1.6 mmol) in THF (10 mL) was added DIAD (0.31 mL, 1.6 mmol). The reaction mixture was stirred overnight, then concentrated under reduced pressure and purified by flash chromatography (30% EtOAc/CH2Cl2) to afford (±)-(4R*,5R*)-5-[(3-chlorophenoxy)methyl]-1-methyl-4-phenylpyrrolidin-2-one (80 mg, 23%) as a colorless oil. TLC (75% EtoAc/25% hexanes) Rf 0.29, CI m/z (rel abundance) 316 ([MH]+, 100%).
Reaction SMILES: [C:1]([C:3]([CH3:9])([CH3:8])[C:4]([NH:6][NH2:7])=O)#[N:2].CCN(CC)CC.Cl.[C:18](=[NH:27])(OC)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CO>[CH3:8][C:3]([C:4]1[NH:6][N:7]=[C:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:27]=1)([CH3:9])[C:1]#[N:2]
Reactant: CC(C)(C#N)C(=O)NN
Reactant: COC(=N)c1ccccc1
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(C)(C#N)c1nc(-c2ccccc2)n[nH]1
Yield: 65 %

Procedure:
2-Cyano-2-methylpropanehydrazide (100 mg, 0.78 mmol) and Et3N (0.1 mL, 0.86 mmol) were added to a solution of methyl benzimidate hydrochloride (100 mg, 0.58 mmol) in dry MeOH (10 mL), and the mixture was heated to reflux for 1 h. The reaction mixture was then concentrated under reduced pressure and the crude product was purified by column chromatography (silica 60-120 mesh, eluant 15% EtOAc in petroleum ether) to get 2-methyl-2-(3-phenyl-1H-1,2,4-triazol-5-yl)propanenitrile (80 mg, yield 51%). 1H NMR (300 MHz, MeOD) δ 7.98-7.95 (m, 2H), 7.52-7.50 (m, 3H), 1.82 (s, 6H). MS (ESI) m/z: Calculated for C12H12N4: 212.11. found: 213.2 (M+H)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH:12]3[CH2:13][CH2:14][CH:9]([CH2:10][CH2:11]3)[N:8]2C(OCC)=O)[CH:2]=1>[OH-].[Na+].C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH:12]3[CH2:13][CH2:14][CH:9]([CH2:10][CH2:11]3)[NH:8]2)[CH:2]=1
Reactant: CCOC(=O)N1C2CCC(CC2)C1c1cccnc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: c1cncc(C2NC3CCC2CC3)c1
Yield: 83 %

Procedure:
(+/-)-3-(3-pyridyl)-2-carboethoxy-2-azabicyclo[2.2.2]octane (XII) (500 mg, 1.92 mmol) was dissolved in a solution of 20% (w/v) NaOH in absolute ethanol (10 mL) and refluxed for 24 h. The organic solvent was evaporated on a rotary evaporator. The pH of the basic residue was adjusted to 9 by addition of a solution of 2N HCl in water and was extracted with ethyl acetate (4×10 mL). The organic extracts were dried over anhydrous K2CO3, and concentrated. The resulting oily residue was purified by distillation under reduced pressure (108°-110° C./0.4 mm Hg) to afford 300 mg (83%) of compound (XIII). 1H NMR (CDCl3): δ 8.62-8.61 (d, 1H), 8.44-8.41 (m, 1H), 7.80-7.72 (m, 1H), 7.24-7.21 (m, 1H), 4.30 (s, 1H), 3.71-3.63(m, 1H), 2.20(m, 1H), 2.0-1.51 (m, 8H), 1.42 (d, 1H).