Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][C:5]=2[C:6]=1[CH3:7]>[Pd].CO>[CH3:1][C:2]1[O:3][C:4]2[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][C:5]=2[C:6]=1[CH3:7]
Reactant: Cc1oc2ccc([N+](=O)[O-])cc2c1C
Agent: [Pd]
Solvent: CO
Product: Cc1oc2ccc(N)cc2c1C

Procedure:
2,3-Dimethyl-5-nitrobenzofuran (13.4 g.) was hydrogenated in 200 ml. of methanol over 0.6 g. of 5% palladium on carbon. The catalyst was removed by filtration and the filtrate was evaporated to dryness to give 2,3-dimethyl-5-aminobenzofuran, m.p. 77°-78° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:20])([CH3:19])[CH2:9][C@@:10]([C:15]([F:18])([F:17])[F:16])([OH:14])[CH2:11][C:12]#[CH:13])=[C:4]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:3]=1.C(N(CC)CC)C.[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[CH:40]=[N:41][C:42]([S:46]([CH3:49])(=[O:48])=[O:47])=[CH:43][C:44]=1I)([CH3:35])([CH3:34])[CH3:33].[Cl-].[NH4+]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[CH:40]=[N:41][C:42]([S:46]([CH3:49])(=[O:48])=[O:47])=[CH:43][C:44]=1[C:13]#[C:12][CH2:11][C@@:10]([OH:14])([C:15]([F:16])([F:18])[F:17])[CH2:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[S:21]([CH3:24])(=[O:22])=[O:23])([CH3:20])[CH3:19])([CH3:35])([CH3:34])[CH3:33]
Reactant: CC(C)(C)OC(=O)Nc1cnc(S(C)(=O)=O)cc1I
Reactant: C#CC[C@](O)(CC(C)(C)c1ccc(Cl)cc1S(C)(=O)=O)C(F)(F)F
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)Nc1cnc(S(C)(=O)=O)cc1C#CC[C@](O)(CC(C)(C)c1ccc(Cl)cc1S(C)(=O)=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 67.9 %

Procedure:
To a solution of (S)-6-(4-chloro-2-methanesulfonylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol (15.6 g, 40.8 mmol), triethylamine (23.0 mL, 165 mmol), and (4-iodo-6-methanesulfonylpyridin-3-yl)carbamic acid tert-butyl ester (18.0 g, 45.2 mmol) in 150 mL of DMF was added CuI (1.6 g, 8.4 mmol) and Pd(PPh3)2Cl2 (3.0 g, 4.3 mmol) as one mixed solid batch. The mixture was stirred at room temperature for 18 hours resulting in the color changing to deep red. Saturated aqueous ammonium chloride solution and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, brine, dried over sodium sulfate, filtered through CELITE® filter aid, and evaporated. The crude material was separated by flash column chromatography using a 0-75% EtOAc/hexanes gradient. Evaporation of the solvent yielded an off-white foam as the pure {4-[(S)-6-(4-chloro-2-methanesulfonylphenyl)-4-hydroxy-6-methyl-4-trifluoromethylhept-1-ynyl]-6-methanesulfonylpyridin-3-yl}carbamic acid tert-butyl ester (18.1 g, 68%).
Reaction SMILES: [C:1]1([CH2:7][S:8][C:9]2[N:10]=[C:11](Cl)[C:12]3[S:17][C:16]([NH2:18])=[N:15][C:13]=3[N:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:20][CH2:21][CH2:22][CH2:23][CH:24]([NH2:27])[CH2:25][OH:26].C(=O)([O-])[O-].[K+].[K+]>>[NH2:18][C:16]1[S:17][C:12]2[C:11]([NH:27][CH:24]([CH2:23][CH2:22][CH2:21][CH3:20])[CH2:25][OH:26])=[N:10][C:9]([S:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:14][C:13]=2[N:15]=1
Reactant: CCCCC(N)CO
Reactant: Nc1nc2nc(SCc3ccccc3)nc(Cl)c2s1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCCCC(CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12
Yield: 17.6 %

Procedure:
5-Phenylmethylthio-7-chloro-thiazolo[4,5-d]pyrimidin-2-ylamin (100 mg, 0.32 mmol), DL-2-amino-1-hexanol (295 μL, 2.3 mmol) and potassium carbonate (124 mg, 0.90 mmol) were heated for 24 hours as in Example 1. The solution was filtered and the solvent was evaporated. The crude product was flash chromatographed on silica (gradient eluent—ammonia:ethylacetate:dichloromethane, 1:69:30 to 1:99:0) resulting in 22 mg (17% yield) of the title compound as a yellow solid.
Reaction SMILES: CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[O:19][C:18](=[O:21])[C:17]([C:22]([OH:24])=O)=[CH:16]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:49][N:50]([CH3:64])[C:51]1[N:56]=[CH:55][C:54]([C:57]2[CH:58]=[C:59]([NH2:63])[CH:60]=[CH:61][CH:62]=2)=[CH:53][CH:52]=1>CN(C=O)C>[CH3:49][N:50]([CH3:64])[C:51]1[N:56]=[CH:55][C:54]([C:57]2[CH:58]=[C:59]([NH:63][C:22]([C:17]3[C:18](=[O:21])[O:19][C:20]4[C:15]([CH:16]=3)=[CH:14][CH:13]=[CH:12][C:11]=4[OH:10])=[O:24])[CH:60]=[CH:61][CH:62]=2)=[CH:53][CH:52]=1
Reactant: O=C(O)c1cc2cccc(O)c2oc1=O
Reactant: CN(C)c1ccc(-c2cccc(N)c2)cn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)c1ccc(-c2cccc(NC(=O)c3cc4cccc(O)c4oc3=O)c2)cn1
Temperature: 25 °C
Yield: 42.2 %

Procedure:
DIEA (0.012 mL, 0.071 mmol) was added to 8-hydroxy-3-carboxy-coumarin (0.013 g, 0.065 mmol) and HATU (0.027 g, 0.071 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(6-dimethylamino-pyridin-3-yl)-phenylamine (0.014 g, 0.065 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.011 g of product in 42% yield: LCMS (ESI) m/z 402 (MH+).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:3]=1.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([CH2:24][CH2:25][NH2:26])=[CH:16]1.CCN(C(C)C)C(C)C.O>CC(O)C>[Cl:8][C:6]1[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:3]=[C:2]([NH:26][CH2:25][CH2:24][C:17]2[C:18]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[NH:15][CH:16]=2)[CH:7]=1
Reactant: NCCc1c[nH]c2ccccc12
Reactant: Clc1cc(Cl)nc(-c2ccccn2)n1
Solvent: O
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: Clc1cc(NCCc2c[nH]c3ccccc23)nc(-c2ccccn2)n1

Procedure:
4,6-Dichloro-2-pyridin-2-yl-pyrimidine (Intermediate F) (1 eq, 8.85 mmol, 2.0 g) and 2-(1H-indol-3-yl)-ethylamine (1 eq, 8.85 mmol, 1.42 g) are dissolved in iPrOH (10 ml). DIPEA (2 eq, 17.7 mmol, 2.29 g) is added and the resulting mixture is heated using microwave radiation at 130° C. for 20 min. The reaction mixture is added to water and extracted with EtOAc. The combined organic layers are washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The crude residue is crystallised from EtOAc giving the title compound [M+H]+=350.
Reaction SMILES: [ClH:1].O1CCOCC1.C([NH:15][CH2:16][C:17](=[O:31])[CH2:18][CH2:19][C:20]([O:22][CH2:23][C:24]([O:26]C(C)(C)C)=[O:25])=[O:21])(OC(C)(C)C)=O>>[ClH:1].[NH2:15][CH2:16][C:17](=[O:31])[CH2:18][CH2:19][C:20]([O:22][CH2:23][C:24]([OH:26])=[O:25])=[O:21]
Reactant: CC(C)(C)OC(=O)COC(=O)CCC(=O)CNC(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Product: NCC(=O)CCC(=O)OCC(=O)O
Reaction time: 1 h
Yield: 96 %

Procedure:
A 4 M solution of hydrogen chloride in dioxane (35 mL; 0.14 mol) was added to the product of 1a (3.3 g; 9.5 mmol) and stirred until the oil dissolved with evolution of gas. After standing one hour, the solvent was evaporated and the residue was triturated with diethyl ether (4×20 mL); the oil solidified to a tan powder. The residue was filtered and dried overnight in a drying pistol at 50° C. and 13 mm Hg. 2.05 g (96%) product was obtained (tan powder).
Reaction SMILES: C[O:2][C:3](=[O:36])[CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[NH:17][C:16]3[CH:18]=[C:19]([C:22](=[O:34])[NH:23][C:24]4[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=4)[CH:20]=[CH:21][C:15]=3[N:14]=2)=[C:8]([CH3:35])[CH:7]=1.[Li+].[OH-]>O1CCCC1>[C:30]([C:27]1[CH:28]=[CH:29][C:24]([NH:23][C:22]([C:19]2[CH:20]=[CH:21][C:15]3[N:14]=[C:13]([C:9]4[C:8]([CH3:35])=[CH:7][C:6]([O:5][CH2:4][C:3]([OH:36])=[O:2])=[CH:11][C:10]=4[CH3:12])[NH:17][C:16]=3[CH:18]=2)=[O:34])=[CH:25][CH:26]=1)([CH3:33])([CH3:32])[CH3:31]
Reactant: COC(=O)COc1cc(C)c(-c2nc3ccc(C(=O)Nc4ccc(C(C)(C)C)cc4)cc3[nH]2)c(C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1cc(OCC(=O)O)cc(C)c1-c1nc2ccc(C(=O)Nc3ccc(C(C)(C)C)cc3)cc2[nH]1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of {4-[6-(4-tert-butylphenylcarbamoyl)-1H-benzoimidazol-2-yl]-3,5-dimethylphenoxy}-acetic acid methyl ester (0.1727 g, 0.356 mmol) in tetrahydrofuran (5 mL) was added LiOH (1 mL of a 4M solution) and the mixture was stirred at ambient temperature for 18 h. The solvent was removed under reduced pressure and the residue was taken up in water, brought to pH 4 and the solid filtered to the title compound. 1H-NMR (DMSO-d6, 400 MHz): δ 12.97 (s, broad, 1H), 12.72 (d, J=24.76 Hz, 1H), 10.11 (d, J=15.16 Hz, 1H), 10.11 (d, J=15.16 Hz, 1H), 8.31 (s, 0.5H), 8.06 (s, 0.5H), 7.75-7.81 (m, 1H), 7.63-7.71 (m, 2.5H), 7.51 (d, J=8.34 Hz, 0.5H,) 7.30 (d, J=8.59 Hz, 2H), 6.71 (s, 2H), 4.68 (s, 2H), 2.03 (s, 6H), 1.22 (s, 9H). MS (m/z) 472.2 (M+1).
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I:10][C:11]1[C:19]([C:20]([NH:22][CH3:23])=[O:21])=[C:18]([I:24])[C:17]([NH:25][C:26](=[O:30])[CH2:27][O:28][CH3:29])=[C:16]([I:31])[C:12]=1[C:13](Cl)=[O:14]>>[I:10][C:11]1[C:19]([C:20]([NH:22][CH3:23])=[O:21])=[C:18]([I:24])[C:17]([NH:25][C:26](=[O:30])[CH2:27][O:28][CH3:29])=[C:16]([I:31])[C:12]=1[C:13]([O:3][CH2:1][CH3:2])=[O:14]
Reactant: CNC(=O)c1c(I)c(NC(=O)COC)c(I)c(C(=O)Cl)c1I
Reactant: CCO
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCOC(=O)c1c(I)c(NC(=O)COC)c(I)c(C(=O)NC)c1I

Procedure:
A solution of 2,4,6-triiodo-5-methoxyacetamido-N-methylisophthalamoyl chloride in N,N-dimethylacetamide (prepared as in Example 3) is treated with absolute ethanol in the presence of potassium carbonate. After the reaction is complete, the inorganic salts are removed by filtration and the filtrate is evaporated to dryness to provide ethyl 2,4,6-triiodo-5-methoxyacetamido-N-methylisophthalamate.
Reaction SMILES: O[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=3)[N:10]=2)[N:3]=1.P(Cl)(Cl)([Cl:24])=O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[Cl:24][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=3)[N:10]=2)[N:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cccc(-c2cccc(-c3nc(C)cc(O)n3)n2)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Cc1cccc(-c2cccc(-c3nc(C)cc(Cl)n3)n2)c1
Yield: 91.9 %

Procedure:
To solution of 4-hydroxy-6-methyl-2-(6-m-tolyl-2-pyridinyl)pyrimidine (5 g) in toluene (100 ml), was added phosphoryl chloride (5 g). The mixture was heated under refluxing for one hourand left to stand to room temperature. Aqueous sodium carbonate solution was added thereto until the reaction solution became about pH 8 to be separated into two layers. Toluene layer was washed with water and dried over anhydrous magnesium sulfate. The toluene layer was concentrated under reduced pressure to obtain 4-chloro-6-methyl-2-(6-m-tolyl-2-pyridinyl)pyrimidine (4.9 g, yield 92%).
Reaction SMILES: [C:1]1([C:11]([N:13]2[CH2:17][CH:16]([CH:18]=O)[CH:15]([CH2:20][N:21]3[CH2:26][CH2:25][CH:24]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)[CH2:14]2)=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[C:1]1([C:11]([N:13]2[CH2:17][CH:16]([CH2:18][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH:15]([CH2:20][N:21]3[CH2:26][CH2:25][CH:24]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)[CH2:14]2)=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: C1COCCN1
Reactant: O=CC1CN(C(=O)c2cccc3ccccc23)CC1CN1CCC(c2ccc(F)cc2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: O=C(c1cccc2ccccc12)N1CC(CN2CCOCC2)C(CN2CCC(c3ccc(F)cc3)CC2)C1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of 0.03 g (0.073 mmol) of 1-(1-naphthoyl)-3-(RS)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(SR)-formylpyrrolidine and 0.013 mL (0.145 mmol) of morpholine in 2 mL of dichloroethane at rt was added 0.046 g (0.27 mmol) of sodium triacetoxyborohydride. After stirring for 1.5 h at rt, the reaction mixture was partitioned between CH2Cl2 and sat'd NaHCO3. The organic fraction was dried over Na2SO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, CH2Cl2: MeOH, 95:5) to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:20][CH:21]2[CH2:38][CH2:37][C:24]3([CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]3)[CH2:23][CH2:22]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[C:16]([CH:17]=2)=[N:15][N:14]([CH3:18])[C:13]=3[CH3:19])=[N:6][CH:7]=1.Cl.CCOC(C)=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:20][CH:21]2[CH2:22][CH2:23][C:24]3([CH2:25][CH2:26][NH:27][CH2:28][CH2:29]3)[CH2:37][CH2:38]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[C:16]([CH:17]=2)=[N:15][N:14]([CH3:18])[C:13]=3[CH3:19])=[N:6][CH:7]=1
Reactant: Cc1c2ccc(Nc3ncc(Cl)c(NC4CCC5(CC4)CCN(C(=O)OC(C)(C)C)CC5)n3)cc2nn1C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Cc1c2ccc(Nc3ncc(Cl)c(NC4CCC5(CCNCC5)CC4)n3)cc2nn1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.7 %

Procedure:
To a solution of tert-butyl 9-((5-chloro-2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecane-3-carboxylate (161.5 mg, 0.30 mmol) in DCM (10 mL) was added a solution of HCl in EtOAc (10 mL, 40 mmol). The reaction mixture was stirred at rt for 2 h and concentrated in vacuo. The residue was dissolved in water (30 mL) and adjusted to pH=10 with a saturated Na2CO3 aqueous solution, then extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/10) to give the title compound as a beige solid (131.6 mg, 100%).
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.O[CH2:44][CH2:45][C:46]1[N:47]=[C:48](/[CH:51]=[CH:52]/[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[O:49][CH:50]=1>O1CCCC1>[CH:51](/[C:48]1[O:49][CH:50]=[C:46]([CH2:45][CH2:44][N:5]2[C:1](=[O:11])[C:2]3=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]3[C:4]2=[O:6])[N:47]=1)=[CH:52]\[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1
Reactant: OCCc1coc(/C=C/c2ccccc2)n1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1CCc1coc(/C=C/c2ccccc2)n1
Reaction time: 4 h
Yield: 95.7 %

Procedure:
Phthalimide (200 mg), triphenylphosphine (357 mg) and diethyl azodicarboxylate (0.214 ml) were added to a solution of 4-(2-hydroxyethyl)-2-(trans-styryl)oxazole (292 mg) in tetrahydrofuran (15 ml) at room temperature, and the mixture was stirred for 4 hours. The solvent of the reaction mixture was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:1) to obtain the title compound (447 mg) as a colorless solid.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[CH2:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8])[CH3:2].[N:13]([O-])=[O:14].[Na+].O>C(O)(=O)C>[CH2:1]([O:3][C:4](=[O:12])[C:5](=[N:13][OH:14])[C:6](=[O:11])[C:7]([F:10])([F:8])[F:9])[CH3:2]
Reactant: O=N[O-]
Reactant: CCOC(=O)CC(=O)C(F)(F)F
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)C(=NO)C(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A stirred solution of 4,4,4-trifluoro-3-oxo-butyric acid ethyl ester (3.822 g, 20.75 mmol) in glacial acetic acid was added dropwise with an aqueous solution of sodium nitrite (4 ml, 20.75 mmol) while maintaining the temperature at 0˜5° C. Upon completion of the addition, 1 ml of water was added. The reaction mixture was stirred in an ice-water bath for 30 minutes and at room temperature for another 3 hours. The solution of 4,4,4-trifluoro-2-hydroxyimino-3-oxo-butyric acid ethyl ester was obtained which was used as such.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH:12]([CH2:17]P(OC)(OC)=O)[C:13]([O:15][CH3:16])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][N:25](C)[C:26](=N)[N:27]([CH3:29])C.N1C=CN=C1C=O>O1CCCC1>[CH2:1]([O:8][C:9]([NH:11]/[C:12](=[CH:17]\[C:26]1[NH:25][CH:24]=[CH:29][N:27]=1)/[C:13]([O:15][CH3:16])=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CN(C)C(=N)N(C)C
Reactant: COC(=O)C(CP(=O)(OC)OC)NC(=O)OCc1ccccc1
Agent: O=Cc1ncc[nH]1
Solvent: C1CCOC1
Product: COC(=O)/C(=C/c1ncc[nH]1)NC(=O)OCc1ccccc1
Temperature: -40 °C
Yield: 40 %

Procedure:
A mixture of methyl 2-{[(benzyloxy)carbonyl]amino}-3-(dimethoxyphosphoryl)-propanoate (1 g, 30 mmol) in tetrahydrofuran (7 ml) was stirred at −40° C. and tetramethylguanidine (380 mg, 33 mmol) was added. The reaction mixture was stirred at −40° C. for 20 minutes and then imidazole-2-carboxaldehyde (317 mg, 33 mmol) was added. The reaction was then allowed to warm to room temperature and was stirred at room temperature for 18 h. The solvent was then removed by evaporation under reduced pressure and the residue dissolved in ethyl acetate and washed with water and then brine. The organic phase was then dried (MgSO4), filtered, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of ethyl acetate:pentane (30:70 to 80:20), to give the title compound, 366 mg, 40% yield.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:18]=[CH:17][CH:16]=[CH:15][C:4]=1[CH2:5][NH:6][CH:7]([CH3:14])[CH2:8][C:9]1[S:10][CH:11]=[CH:12][CH:13]=1.Cl.O1CCO[CH2:21]1>>[ClH:2].[Cl:2][C:3]1[CH:18]=[CH:17][CH:16]=[CH:15][C:4]=1[CH2:5][N:6]1[CH:7]([CH3:14])[CH2:8][C:9]2[S:10][CH:11]=[CH:12][C:13]=2[CH2:21]1
Reactant: C1COCO1
Reactant: CC(Cc1cccs1)NCc1ccccc1Cl
Agent: Cl
Product: CC1Cc2sccc2CN1Cc1ccccc1Cl
Temperature: 25 °C
Reaction time: 6 h
Yield: 63 %

Procedure:
N-2-chlorobenzyl-1-methyl-2-(2-thienyl)ethylamine HCl (16.4 g) is suspended in 50 ml of 1,3-dioxolane. Hydrochloric acid (37% concentration) (0.2 ml) is added and the temperature of the reaction mixture is brought to 80° C. for 6 hours. When the reaction is complete, the mixture is cooled to room temperature, and the precipitation of the product is completed by adding 50 ml of ethyl acetate. The crystalline product is filtered, washed with ethyl acetate and dried under vacuum at 60° C. 5-(2-chlorobenzyl)-6-methyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine HCl (10.7 g, 63% yield) is obtained having a m.p. 179-180° C.
Reaction SMILES: C1([Si:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)([Cl:9])[Cl:8])C=CC=CC=1.[Cl:16][SiH2]Cl>Cl>[C:10]1([Si:7]([Cl:8])([Cl:9])[Cl:16])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: Cl[SiH2]Cl
Reactant: Cl[Si](Cl)(c1ccccc1)c1ccccc1
Agent: Cl
Product: Cl[Si](Cl)(Cl)c1ccccc1
Temperature: 70 °C
Yield: 279.6 %

Procedure:
380 g of diphenyldichlorosilane (in which 0.7 g of hydrogen chloride has been dissolved beforehand by bubbling in the gas) and 22.5 g of aluminium chloride are introduced into the flask. 80 cm3 of trichlorosilane are run in, the mixture is heated to 70°C and then 477 g of trichlorosilane are introduced gradually over the course of 7 hours 30 minutes, whilst distilling the resulting dichlorosilane as it is formed. A distillate weighing 79 g, containing 60.8 g of dichlorosilane, is obtained. 356 g of phenyltrichlorosilane are obtained on distilling the mixture remaining in the flask.
Reaction SMILES: [H-].[Na+].[CH3:3][CH:4]([CH2:6][CH2:7][CH:8]([OH:14])[C:9]([CH3:13])=[CH:10][CH2:11][CH3:12])[CH3:5].S(OC)(O[CH3:19])(=O)=O.[OH-].[Na+]>C1C=CC=CC=1.O.CCOCC.CO>[CH3:19][O:14][CH:8]([C:9]([CH3:13])=[CH:10][CH2:11][CH3:12])[CH2:7][CH2:6][CH:4]([CH3:5])[CH3:3]
Reactant: COS(=O)(=O)OC
Reactant: CCC=C(C)C(O)CCC(C)C
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: c1ccccc1
Solvent: CO
Product: CCC=C(C)C(CCC(C)C)OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61.4 %

Procedure:
6.13 g of a 55-60% sodium hydride dispersion in 100 ml of benzene are placed in a reaction vessel equipped with stirrer, thermometer, reflux condenser and dropping funnel and a solution of 20.0 g of 2,6-dimethyl-6-nonen-5-ol in 100 ml of benzene is added dropwise thereto over a period of 30 minutes while stirring at room temperature. In order to complete the reaction, the mixture is held at reflux temperature for 12 hours. The mixture is subsequently cooled to 20° C. At this temperature there are gradually added dropwise 20.7 g of dimethyl sulphate so that the temperature does not exceed 35° C. (exothermic reaction). After completion of the addition, the mixture, which becomes thicker, is heated to reflux temperature for a further 4 hours, then cooled and treated with 25 ml of methanol. After 5 minutes, there is added dropwise a solution of 6.7 g of sodium hydroxide in 40 ml of water and the mixture is again heated to reflux temperature. After cooling, the product is taken up in ether, washed neutral with water and the solvent is distilled off over a Vigreux column. The crude product remaining behind is rectified under a water-jet vacuum with the addition of 0.1 g of sodium carbonate and yields 13.3 g (61.7% of theory) of pure 5-methoxy-2,6-dimethyl-6-nonene of boiling point 78° C./12 Torr, nD20 =1.4339. Odour: sweet, fruity, powdery, green.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([C:9]#[C:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:6]=[CH:7][CH:8]=1.[I-].[Li+].O.Cl>N1C(C)=CC(C)=CC=1C>[OH:2][C:3]1[CH:4]=[C:5]([C:9]#[C:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:6]=[CH:7][CH:8]=1
Reactant: CCCCCCC#Cc1cccc(OC)c1
Agent: Cl
Agent: [I-]
Agent: [Li+]
Solvent: Cc1cc(C)nc(C)c1
Solvent: O
Product: CCCCCCC#Cc1cccc(O)c1

Procedure:
1-(3-Methoxyphenyl)-oct-1-yne, (6.50 g, 0.03M), was dissolved in 2,4,6-collidine, (100 ml), and anhydrous lithium iodide (20.08 g, 0.15M), added. The reaction was stirred under nitrogen at reflux temperature for 48 h, then cooled and poured intro water, (500 ml), and acidified with dilute hydrochloric acid. The product was extracted into ethyl acetate, (twice), and the organic phases combined, washed with water (twice) and dried, (MgSO4). Evaporation of the solvent in vacuo yielded the crude product as a brown oil, which was purified by chromatography on silica gel, eluting with dichloromethane/n-hexane [1:1] to chloroform. 5.40 g (90%) of product was collected as a colourless oil. νmax (film) 1580, 1590, 1605, 2230 (weak) 3400 cm-1 ; δ(CDCl3) 0.85 (3H, distorted t, terminal CH3), 1.39 (8H, m, alkylene chain), 2.32 (2H, t, J 6 Hz, acetylenic CH2), 4.77 (1H, s, OH, exchanged with D2O), 6.78 (2H, m, aromatics), 7.02 (2H, m, aromatics).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8](=[N:10][C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[Cl:19])[CH3:9])[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[C:27](=[O:29])[CH3:28].[Cl-].[NH4+]>C(OCC)C.CCCCCC>[Cl:19][C:12]1[CH:13]=[C:14]([CH3:18])[CH:15]=[C:16]([CH3:17])[C:11]=1[N:10]=[C:8]([C:6]1[N:7]=[C:2]([C:27](=[O:29])[CH3:28])[CH:3]=[CH:4][CH:5]=1)[CH3:9]
Reactant: CC(=Nc1c(C)cc(C)cc1Cl)c1cccc(Br)n1
Reactant: CC(=O)N(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CCOCC
Product: CC(=O)c1cccc(C(C)=Nc2c(C)cc(C)cc2Cl)n1
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 47 %

Procedure:
2.00 g (0.0059 mol) of [1-(6-bromopyridin-2-yl)ethylidene](2-chloro-4,6-dimethylphenyl)amine were dissolved in 25 ml of diethyl ether and cooled to −70° C. 3.70 ml (0.0059 mol) of a 1.6 M solution of butyllithium in hexane were added dropwise over a period of 15 minutes. The temperature rose to −40° C. and the mixture was stirred for another 30 minutes. The mixture was cooled to −70° C. and 0.52 g (0.0059 mol) of N,N-dimethylacetamide was added dropwise and the mixture was stirred at room temperature for another three hours. The reaction mixture was stirred with 5 ml of a saturated ammonium chloride solution. The aqueous phase was extracted twice with diethyl ether. The combined organic phases were dried over Na2SO4, filtered and the solvent was distilled off under reduced pressure. This gave 0.83 g (0.0028 mol) of the product in a yield of 47%.