Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])[CH2:2][CH:3]=[CH2:4].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:50][O:51][C@:52]1([C:61]2[CH:62]=[C:63]([C:67]3[CH:72]=[CH:71][CH:70]=[C:69]([CH:73]=[CH2:74])[CH:68]=3)[CH:64]=[CH:65][CH:66]=2)[CH2:56][NH:55][C@H:54]([C:57]([O:59][CH3:60])=[O:58])[CH2:53]1>C(Cl)Cl>[CH2:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([N:55]1[CH2:56][C@:52]([O:51][CH3:50])([C:61]2[CH:62]=[C:63]([C:67]3[CH:72]=[CH:71][CH:70]=[C:69]([CH:73]=[CH2:74])[CH:68]=3)[CH:64]=[CH:65][CH:66]=2)[CH2:53][C@H:54]1[C:57]([O:59][CH3:60])=[O:58])=[O:12])=[O:7])[CH2:2][CH:3]=[CH2:4]
Reactant: C=Cc1cccc(-c2cccc([C@@]3(OC)CN[C@H](C(=O)OC)C3)c2)c1
Reactant: C=CCCOC(=O)N[C@H](C(=O)O)C(C)(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CCCOC(=O)N[C@H](C(=O)N1C[C@](OC)(c2cccc(-c3cccc(C=C)c3)c2)C[C@H]1C(=O)OC)C(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 68.2 %

Procedure:
(S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid (255 mg, 1.111 mmol), DIEA (0.40 mL, 2.223 mmol) and HATU (310 mg, 0.815 mmol) were added to a solution of (2S,4R)-methyl 4-methoxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylate (250 mg 0.741 mmol) in DCM (3 mL). The reaction was stirred at r.t. for 2 hrs. The reaction was evaporated and purified by flash chromatography on the Biotage (10-40% EtOAc:Hex) to give (2S,4R)-methyl 1-((S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylate (277 mg, 0.505 mmol, 68% yield) as a white foam. LCMS: rt=2.31 min. [M+H]+=549; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent 13=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min, inj. vol.=5 uL; wavelength=220.
Reaction SMILES: [CH2:1]([P:3]([CH2:10][CH2:11][OH:12])(=[O:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2].CC(C)=[O:15].OS(O)(=O)=O.O=[Cr](=O)=O.C(O)(C)C>CC(C)=O>[CH2:1]([P:3]([O:4][CH2:5][CH2:6][CH2:7][CH3:8])([CH2:10][C:11]([OH:15])=[O:12])=[O:9])[CH3:2]
Reactant: CCCCOP(=O)(CC)CCO
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Product: CCCCOP(=O)(CC)CC(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 8.1 %

Procedure:
19.4 g (0.1 mol) of butyl ethyl(2-hydroxyethyl)phosphinate (prepared as in Example 6) in 500 ml of acetone were admixed with 0.11 mol of Jones reagent (12.7 g of chromium trioxide in 36.7 ml of water and 11.0 ml of concentrated sulfuric acid) at 0° C. by dropwise addition. The reaction mixture was subsequently stirred for 3½ hours with ice cooling and for 1 hour at room temperature. Following addition of 12 ml of isopropanol, the mixture is poured onto ice-water. Volatile constituents are then distilled off in vacuo. The residue was taken up in tetrahydrofuran and extracted. Insoluble salts were filtered off. The solvent of the filtrate was removed in vacuo and the residue was recrystallized from acetone to obtain 1.68 g (81% of theory) of 2-(ethylbutoxyphosphinyl)acetic acid as colorless solid.
Reaction SMILES: I.[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[C:7]([C:11]=1[N+:12]([O-:14])=[O:13])=[N:8][Se][N:10]=2.OS([O-])=O.[Na+].[OH-].[Na+]>Cl>[Cl:2][C:3]1[C:11]([N+:12]([O-:14])=[O:13])=[C:7]([NH2:8])[C:6]([NH2:10])=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])c1c(Cl)ccc2n[se]nc12
Agent: Cl
Agent: I
Agent: O=S([O-])O
Product: Nc1ccc(Cl)c([N+](=O)[O-])c1N
Reaction time: 2 h
Yield: 85.6 %

Procedure:
At room temperature, an aqueous solution of hydroiodic acid (48%, 25 ml) was added to a solution of 5-chloro-4-nitro-benzo[1,2,5]selenadiazole (8.14 g, 31.01 mmol) in concentrated aqueous hydrochloric acid (76 ml). After 2 hours at room temperature, a 5% aqueous solution of NaHSO3 (150 ml) was added, and the mixture was stirred for 15 minutes. At 0° C., concentrated aqueous NaOH solution was added until the pH value reached 8. The mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (4.98 g, 86%), which was used in the next transformation without further purification. 1H NMR (400 MHz, d6-acetone): δ=6.81 (d, J=7.7 Hz, 1H), 6.68 (d, J=7.7 Hz, 1H), 5.12 (br s, 2H), 4.78 (br s, 2H). MS (ES−): 186.2 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.C([SiH2][O:24][C:25](C)(C)[C:26]1[CH:27]=[C:28]([C:32]2[O:36][CH:35]=[N:34][C:33]=2[C:37](O)=[O:38])[CH:29]=[CH:30][CH:31]=1)(C)(C)C>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[CH:16][C:15]([NH:18][C:37]([C:33]3[N:34]=[CH:35][O:36][C:32]=3[C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([CH2:25][OH:24])[CH:27]=3)=[O:38])=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1cccc(-c2ocnc2C(=O)O)c1
Reactant: CC1(c2ccc(Cn3ccc(N)n3)o2)OCCO1
Product: CC(=O)c1ccc(Cn2ccc(NC(=O)c3ncoc3-c3cccc(CO)c3)n2)o1

Procedure:
Following general procedure B followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-3-ylamine and 5-[3-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=0.86 min; [M+H]+=407.37.
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:24])[NH:6][N:7]=[C:8]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1.Cl[CH2:39][CH2:40][N:41]([CH3:43])[CH3:42]>O.CN(C)C=O>[CH3:42][N:41]([CH3:43])[CH2:40][CH2:39][N:6]1[C:5](=[O:24])[C:4]([C:1](=[O:3])[CH3:2])=[C:9]([C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)[C:8]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[N:7]1
Reactant: CC(=O)c1c(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2)n[nH]c1=O
Reactant: CN(C)CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1c(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2)nn(CCN(C)C)c1=O
Reaction time: 4 h
Yield: 63 %

Procedure:
4-Acetyl-5,6-bis(p-chlorophenyl)-2H-pyridazin-3-one (20.0 g), potassium carbonate (9.0 g) and 30 ml of a toluene solution of N-(2-chloroethyl)dimethylamine (0.34 g/ml) and dimethylformamide (150 ml) were stirred at 80° C. for 18 hours. A second equivalent of the amine was added and heating continued for an additional four hours. The mixture was cooled, poured into water and the suspension extracted with ethyl acetate. The combined organic extracts were dried and evaporated in vacuo. Following purification by dry column silica gel chromatography and recrystallization, the title compound was obtained (63 percent yield), m.p. 149°-150° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH2:5][O:6][C@@H:7]([CH3:17])[CH2:8][NH:9]C(OC(C)(C)C)=O)[CH3:2].[ClH:19]>C(OCC)(=O)C>[ClH:19].[CH2:1]([O:3][C:4](=[O:18])[CH2:5][O:6][C@@H:7]([CH3:17])[CH2:8][NH2:9])[CH3:2]
Reactant: CCOC(=O)CO[C@@H](C)CNC(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: CCOC(=O)CO[C@@H](C)CN
Temperature: 25 °C
Reaction time: 3 h
Yield: 76 %

Procedure:
1.2 g (4.59 mmol) of (S)-(2-t-butoxycarbonylamino-1-methyl-ethoxy)-acetic acid ethyl ester was dissolved in 20 mL of ethyl acetate saturated with hydrochloric acid gas, followed by stirring at room temperature for 3 hours. The solvent was distilled off under reduced pressure, then the residue was purified by column chromatography to give 699 mg (3.49 mmol) of the title compound in a yield of 76%.
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]12[CH:22]=[CH:21][CH:20]=[CH:19][CH:9]1[CH2:10][CH:11]2[CH2:12][N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[N+]=[N-].[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1.CCOCC>[NH2:1][CH2:4][CH2:5][CH2:6][O:7][C:8]12[CH:22]=[CH:21][CH:20]=[CH:19][CH:9]1[CH2:10][CH:11]2[CH2:12][N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: [N-]=[N+]=NCCCOC12C=CC=CC1CC2CN1CCCCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: NCCCOC12C=CC=CC1CC2CN1CCCCC1

Procedure:
A solution of the azido benzocyclobutenylmethyl compound (0.8 g) (step 8 above) in THF (5.2 ml) is added over a period of 30 min to a suspension of LAH (0.125 g) in anhydrous ether (16.5 ml) stirred under nitrogen. The mixture is refluxed for about 2 hours and cooled. Water (0.125 ml), aqueous NaOH (15% solution, 0.125 ml) and water (3.75 ml) are added to the cooled mixture which is filtered. The solid is washed with ether and the filtrate dried over Na2SO4. The dried filtrate is filtered, evaporated in vacuo and chromatographed (silica gel) eluting with 1:1 ethyl acetate/MeOH. The pure fractions are combined and evaporated in vacuo yielding an oil. NMR analysis identifies the oil as the desired product.
Reaction SMILES: [P:1]([O:5][CH2:6][C@@H:7]([OH:16])[C@@H:8]([OH:15])[C@H:9]([OH:14])[C:10](=[O:13])[CH2:11][OH:12])([O-:4])([O-:3])=[O:2].[Na+].[Na+]>O>[P:1]([O:5][CH2:6][C@@H:7]([OH:16])[C@@H:8]([OH:15])[C@H:9]([OH:14])[C:10](=[O:13])[CH2:11][OH:12])([OH:3])([OH:4])=[O:2]
Reactant: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)COP(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)COP(=O)(O)O
Reaction time: 1176 h
Yield: 93.5 %

Procedure:
To 18.5 ml of 0.67 M cis-[Pt(NH3)2 (H2O)2 ](NO3)2, 4.5 grams of disodium D-fructose-6-phosphate were added. The solution was stoppered with a porous plug and stirred for 49 days. At the end of that time, a blue, water-insoluble precipitate had formed. It was collected, and then washed by alternate centrifugation and resuspension. The precipitate was vacuum dried to yield 3.6 grams of the above-identified complex.
Reaction SMILES: I[CH2:2][CH2:3][CH:4]1[CH2:10][CH2:9][C:8]2[C:11]([O:21][CH3:22])=[C:12]([O:19][CH3:20])[C:13]([O:17][CH3:18])=[C:14]([O:15][CH3:16])[C:7]=2[CH2:6][CH2:5]1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:2][CH2:3][CH:4]2[CH2:10][CH2:9][C:8]3[C:11]([O:21][CH3:22])=[C:12]([O:19][CH3:20])[C:13]([O:17][CH3:18])=[C:14]([O:15][CH3:16])[C:7]=3[CH2:6][CH2:5]2)=[CH:26][CH:25]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: COc1c2c(c(OC)c(OC)c1OC)CCC(CCI)CC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1c2c(c(OC)c(OC)c1OC)CCC(CCOc1ccc(Cl)cc1)CC2
Temperature: 25 °C
Reaction time: 12 h
Yield: 96.2 %

Procedure:
The mixture of 7-(2-iodoethyl)-1,2,3,4-tetramethoxy-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene (1.64 g), 4-chlorophenol (602 mg), potassium carbonate (1.08 g), and DMF (16 ml) was stirred at room temperature for 12 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride and dried. The solvent was removed in vacuo. The residue was purified by alumina column chromatography (toluene) to yield the entitled compound (1.58 g) as crystals.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[CH:8][CH:7]=1.[I-].[Na+].[CH3:19][CH:20]1[CH2:24][CH2:23][CH2:22][NH:21]1>C(#N)C>[CH3:19][CH:20]1[CH2:24][CH2:23][CH2:22][N:21]1[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[CH:8][CH:7]=1
Reactant: ClCCCOc1ccc(-c2nccs2)cc1
Reactant: CC1CCCN1
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: CC1CCCN1CCCOc1ccc(-c2nccs2)cc1
Temperature: 85 °C
Reaction time: 8 h
Yield: 27 %

Procedure:
A solution of 2-[4-(3-chloropropoxy)phenyl]-1,3-thiazole i88 (120 mg, 1 eq, 0.47 mmol) in acetonitrile (1 ml) is added to a solution of sodium iodide (10 mg, 0.1 eq, 0.07 mmol) and 2-methylpyrrolidine (0.1 ml, 2 eq, 0.9 mmol) in acetonitrile (1 ml). The mixture is stirred at 85° C. overnight, filtered, washed with acetonitrile, and concentrated under reduced pressure. Purification of the residue by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 96/4/0.4) affords 40 mg of 2-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-1,3-thiazole 83.
Reaction SMILES: C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH2:23]([O:25][C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([O:41][CH2:42][CH3:43])[C:34]=1[C:35]1[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=1)[C:29]([OH:31])=O)[CH3:24].Cl.[CH3:45][C:46]([CH3:73])([CH3:72])[C:47]([O:49][CH2:50][N:51]1[N:55]=[N:54][C:53]([C:56]2[CH:57]=[C:58]3[C:68](=[CH:69][CH:70]=2)[O:67][C:61]2([CH2:66][CH2:65][NH:64][CH2:63][CH2:62]2)[CH2:60][C:59]3=[O:71])=[N:52]1)=[O:48]>O.CN(C=O)C.CCN(CC)CC>[CH3:45][C:46]([CH3:73])([CH3:72])[C:47]([O:49][CH2:50][N:51]1[N:55]=[N:54][C:53]([C:56]2[CH:57]=[C:58]3[C:68](=[CH:69][CH:70]=2)[O:67][C:61]2([CH2:62][CH2:63][N:64]([C:29]([C:28]4[CH:32]=[C:33]([O:41][CH2:42][CH3:43])[C:34]([C:35]5[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=5)=[C:26]([O:25][CH2:23][CH3:24])[CH:27]=4)=[O:31])[CH2:65][CH2:66]2)[CH2:60][C:59]3=[O:71])=[N:52]1)=[O:48]
Reactant: CC(C)(C)C(=O)OCn1nnc(-c2ccc3c(c2)C(=O)CC2(CCNCC2)O3)n1
Reactant: CCOc1cc(C(=O)O)cc(OCC)c1-c1cnn(C)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOc1cc(C(=O)N2CCC3(CC2)CC(=O)c2cc(-c4nnn(COC(=O)C(C)(C)C)n4)ccc2O3)cc(OCC)c1-c1cnn(C)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Et3N (223 μL), HOBT (123 mg) and WSC hydrochloride (154 mg) were added to a DMF (8 mL) solution of 3,5-diethoxy-4-(1-methyl-1H-pyrazol-4-yl)benzoic acid (194 mg) and [5-(4-oxospiro[chroman-2,4′-piperidin]-6-yl)-2H-tetrazol-2-yl]methyl 2,2-dimethylpropanoate hydrochloride (349 mg), and stirred overnight at room temperature. The reaction liquid was poured into saturated saline water, extracted with ethyl acetate, and the organic layer was washed with water and saturated saline water. The organic layer was dried with sodium sulfate, filtered, concentrated, and purified through silica gel column chromatography (hexane/EtOAc) to obtain the title compound. 1H-NMR (400 MHz, CDCl3) δ: 8.69 (1H, d, J=4.0 Hz), 8.32 (1H, dd, J=8.0, 4.0 Hz), 8.14 (1H, s), 7.97 (1H, s), 7.17 (1H, d, J=8.0 Hz), 6.64 (2H, s), 6.50 (2H, s), 4.32-4.18 (1H, m), 4.08 (4H, q, J=8.0 Hz), 3.94 (3H, s), 3.64-3.20 (3H, m), 2.97 (2H, s), 2.10-1.75 (4H, m), 1.37 (6H, t, J=8.0 Hz), 1.22 (9H, s). MS [M+H]+=672.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH:5]=[C:4]([C:18]([F:21])([F:20])[F:19])[N:3]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1>>[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:2]2[N:3]=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:5]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)[N:7]=2)[CH:23]=1
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(Cl)n2)cc1
Reactant: OB(O)c1cccnc1
Product: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-c3cccnc3)n2)cc1

Procedure:
The title compound was prepared from 2-chloro-4-(4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidine (example A.2) (0.33 g, 1.0 mmol) and commercially available 3-pyridineboronic acid (0.184 g, 1.5 mmol) according to the general procedure IVb. Obtained as a light yellow solid (0.03 g, 8%). MS (ISP) 370.1 [(M+H)+]; mp 134° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@:9]12[CH2:17][N:16]([C@@H](C3C=CC=CC=3)C)[CH2:15][C@@H:14]1[CH2:13][CH:12]=[CH:11][CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>[C].[Pd].C(O)C>[C:1]([O:5][C:6]([NH:8][C@:9]12[CH2:17][NH:16][CH2:15][C@@H:14]1[CH2:13][CH2:12][CH2:11][CH2:10]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: [H][H]
Reactant: C[C@H](c1ccccc1)N1C[C@@H]2CC=CC[C@@]2(NC(=O)OC(C)(C)C)C1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@]12CCCC[C@H]1CNC2

Procedure:
A 10% palladium-carbon catalyst (406 mg, 100 wt %) was added to a solution of (1S,6S)-1-tert-butoxycarbonylamino-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-ene (406 mg, 1.18 mmol) in ethanol (11.8 mL) in a nitrogen atmosphere. After the atmosphere was replaced with hydrogen, the mixture was stirred in a hydrogen atmosphere at 40° C. to 50° C. for seven hours. After the atmosphere was replaced with nitrogen, the reaction solution was filtered through Celite and concentrated under reduced pressure to give the title compound quantitatively.
Reaction SMILES: [C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][CH2:12][OH:13])[CH2:8][CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:18]1[N:23]=[C:22]([O:24][CH3:25])[C:21]([N+:26]([O-:28])=[O:27])=[CH:20][N:19]=1.O>C1COCC1>[C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][CH2:12][O:13][C:18]1[N:23]=[C:22]([O:24][CH3:25])[C:21]([N+:26]([O-:28])=[O:27])=[CH:20][N:19]=1)[CH2:8][CH2:9][CH3:10])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCN(CCO)C(=O)OC(C)(C)C
Reactant: COc1nc(Cl)ncc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCCN(CCOc1ncc([N+](=O)[O-])c(OC)n1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (2-hydroxy-ethyl)-propyl-carbamic acid tert-butyl ester (1.07 g, 5.28 mmol) in THF (40 ml) at 0° C. was added NaH (0.25 g, 5.80 mmol). After stirring the suspension at 0° C. for 30 minutes a solution of 2-chloro-4-methoxy-5-nitropyrimidine (1 g, 5.28 mmol) in THF (10 ml) was added and the mixture was stirred at room temperature for 16 h. The mixture was added to water, which was extracted three times with dichloromethane. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to obtain the title compound.
Reaction SMILES: C(OC(=O)[NH:10][CH:11]([C:13](=[O:33])[NH:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:16]=1[C:24](=O)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Cl:31])[CH3:12])C1C=CC=CC=1.C1(C)C=CC=CC=1>C(O)(=O)C>[Cl:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:24]1[C:16]2[CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[CH:19]=[CH:20][C:15]=2[NH:14][C:13](=[O:33])[CH:11]([CH3:12])[N:10]=1
Reactant: CC(NC(=O)OCc1ccccc1)C(=O)Nc1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1Cl
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CC1N=C(c2ccccc2Cl)c2cc([N+](=O)[O-])ccc2NC1=O

Procedure:
35 g of the foregoing propionoanilide are heated to reflux in 40 ml of glacial acetic acid and 200 ml of absolute toluene for 15 minutes. The residue obtained after distillation of the solvent is treated with methylene chloride and 10% sodium bicarbonate solution. The methylene chloride solution is washed twice with 10% sodium bicarbonate solution and once with water, dried over sodium sulfate, filtered and concentrated. The residue is taken up in benzene, some racemate formed crystallising out and being filtered off. The benzene solution is evaporated and the residue crystallised from ether to give (+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one which melts at 198°-200° C and exhibits a rotation of [α]25D =+252.1° (in methylene chloride, 1%).
Reaction SMILES: [CH3:1][S:2][C:3]1[S:4][C:5]2[CH:11]=[C:10]([CH2:12][N:13]3[C:17]4=[N:18][CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=[C:16]4[N:15]=[CH:14]3)[CH:9]=[CH:8][C:6]=2[N:7]=1.C1C=C(Cl)C=C(C(OO)=[O:34])C=1>C(Cl)Cl>[CH3:1][S:2]([C:3]1[S:4][C:5]2[CH:11]=[C:10]([CH2:12][N:13]3[C:17]4=[N:18][CH:19]=[C:20]([C:22]([F:25])([F:23])[F:24])[CH:21]=[C:16]4[N:15]=[CH:14]3)[CH:9]=[CH:8][C:6]=2[N:7]=1)=[O:34]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1nc2ccc(Cn3cnc4cc(C(F)(F)F)cnc43)cc2s1
Solvent: ClCCl
Product: CS(=O)c1nc2ccc(Cn3cnc4cc(C(F)(F)F)cnc43)cc2s1
Reaction time: 2 h
Yield: 85.7 %

Procedure:
A mixture of 2-(methylthio)-6-((6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazole (200 mg, 0.53 mmol) and m-CPBA (114 mg, 0.66 mmol) in DCM (5 mL) was stirred in an ice-water bath for 2 h. The mixture was diluted with DCM and washed with aq Na2S2O3, aq NaHCO3 and water. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to afford 2-(methylsulfinyl)-6-((6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazole as a yellow solid (180 mg, 87.8%). 1H NMR (300 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.77 (s, 1H), 8.59 (s, 1H), 8.23 (s, 1H), 8.08 (d, J=8.1 Hz, 1H), 7.66-7.62 (m, 1H), 5.77 (s, 2H), 3.06 (s, 3H). LCMS (ESI) m/z 397 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:25])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:23])[C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)=[CH:10][C:9]=2[F:24])[CH2:4]1.Cl[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1>>[CH3:1][N:2]([CH3:25])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:23])[C:16]3[CH:21]=[CH:20][C:19]([O:22][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)=[CH:18][CH:17]=3)=[CH:10][C:9]=2[F:24])[CH2:4]1
Reactant: CN(C)[C@@H]1CCN(c2ccc(NC(=O)c3ccc(O)cc3)cc2F)C1
Reactant: Clc1ccccn1
Product: CN(C)[C@@H]1CCN(c2ccc(NC(=O)c3ccc(Oc4ccccn4)cc3)cc2F)C1

Procedure:
(R)-N-[4-(3-Dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-4-hydroxybenzamide was reacted with 2-chloropyridine by method R. This resulted in the product with the molecular weight of 434.52 (C25H27N4O2); MS (ESI): 435 (M+H+).
Reaction SMILES: [NH:1]1[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]1=[O:3].[C:10]([O:14][C:15]([O:17][CH2:18][C@@:19]1([C:32]#[CH:33])[O:23][C@@H:22](OC(OC(C)(C)C)=O)[CH:21]=[CH:20]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:10]([O:14][C:15]([O:17][CH2:18][C@@:19]1([C:32]#[CH:33])[O:23][C@@H:22]([N:1]2[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]2=[O:3])[CH:21]=[CH:20]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]
Reactant: C#C[C@@]1(COC(=O)OC(C)(C)C)C=C[C@H](OC(=O)OC(C)(C)C)O1
Reactant: Cc1c[nH]c(=O)[nH]c1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: C#C[C@@]1(COC(=O)OC(C)(C)C)C=C[C@H](n2cc(C)c(=O)[nH]c2=O)O1
Temperature: 55 °C
Reaction time: 0.5 h
Yield: 70.6 %

Procedure:
Thymine (16.7 g), N,N′-dimethylformamide (162 g), and tetrakis(triphenylphosphine)palladium(0) (917 mg) were added to a glass reactor under nitrogen, and the mixture was heated to 55° C. Then, a solution of (2S,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-t-butoxycarbonyloxy-2,5-dihydrofuran (β/α=>99/1) (9.0 g) in N,N′-dimethylformamide was added dropwise thereto, and the mixture was stirred for 30 minutes. The reaction mixture was filtered, and water was added to the filtrate, followed by stirring for phase separation. The thus-separated organic layer was concentrated. The residue was purified through recrystallization from acetonitrile and toluene, to thereby yield 6.5 g of (2R,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-(thymin-1-yl)-2,5-dihydrofuran (yield: 72%, β/α=>99/1). The 1H-NMR data of the compound are as follows.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[CH3:11][N:12]([CH3:25])[C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1)[C:16]#N.C(C(C(C([O-])=O)O)O)([O-])=[O:27].[K+].[Na+]>C(Cl)Cl>[CH3:11][N:12]([CH3:25])[C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1)[CH:16]=[O:27]
Reactant: CN(C)c1cc(C#N)cc(C(F)(F)F)c1
Reactant: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Agent: [K+]
Solvent: ClCCl
Product: CN(C)c1cc(C=O)cc(C(F)(F)F)c1
Reaction time: 2 h

Procedure:
Diisobutylaluminum hydride (10 mL of a 1M solution in methylene chloride) is added dropwise to a solution of 3-dimethylamino-5-trifluoromethylbenzonitrile (1.06 g) in methylene chloride (25 mL) at 0° C. and the mixture stirred for 2 hours. While still at 0° C. a saturated aqueous solution of sodium potassium tartrate (8 mL) is slowly added and the solution is stirred for 1.5 hours. The reaction mixture is then extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to provide the desired product as a yellow solid (0.97 g).