Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: BrC1C=CC(O)=C(C2C=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[C:21]5[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=5[N:19]=4)[CH:14]=3)[N:9]=2)C=1.[OH:37][C:38]1[CH:39]=[C:40]([C:45](=O)[CH3:46])[CH:41]=[C:42]([OH:44])[CH:43]=1.[OH-].[K+]>C(O)C>[CH:23]1([N:22]2[C:21]3[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=3[N:19]=[C:18]2[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[N:9]=[C:45]([C:40]2[CH:39]=[C:38]([OH:37])[CH:43]=[C:42]([OH:44])[CH:41]=2)[CH:46]=[CH:16]3)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(Br)ccc4O)ccc3c1)n2C1CCCCC1
Reactant: CC(=O)c1cc(O)cc(O)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(O)cc(O)c4)ccc3c1)n2C1CCCCC1
Yield: 18 %

Procedure:
Following the procedure and workup for Compound 354, Compound 354e (100 mg, 0.256 mmol) was reacted with 1-(3,5-dihydroxy-phenyl)-ethanone (0.256 mmol) in ethanol (2 mL) using 10% w/v KOH in ethanol (506 μL, 0.64 mmol) to produce the title compound (22 mg, 18% yield).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:34][OH:35])[C:8]([NH:10][CH:11]2[C:32](=[O:33])[N:13]3[C:14]([C:19]([O:21]CC4C=CC([N+]([O-])=O)=CC=4)=[O:20])=[C:15]([Cl:18])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.CO.O>[C].[Pd].O1CCCC1>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:34][OH:35])[C:8]([NH:10][CH:11]2[C:32](=[O:33])[N:13]3[C:14]([C:19]([OH:21])=[O:20])=[C:15]([Cl:18])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: Nc1nc(C(=NO)C(=O)NC2C(=O)N3C(C(=O)OCc4ccc([N+](=O)[O-])cc4)=C(Cl)CS[C@H]23)cs1
Agent: [Pd]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Nc1nc(C(=NO)C(=O)NC2C(=O)N3C(C(=O)O)=C(Cl)CS[C@H]23)cs1
Yield: 34.2 %

Procedure:
4-Nitrobenzyl 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-chloro-3-cephem-4-carboxylate (syn isomer, 5.0 g.), 10% palladium carbon (3.0 g.), methanol (100 ml.), water (10 ml.) and tetrahydrofuran (150 ml.) were treated in a similar manner to that of Example 37-(2), to give 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-chloro-3-cephem-4-carboxylic acid (syn isomer, 1.28 g.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][CH:19]3[CH2:23][CH2:22][O:21][CH2:20]3)=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13](O)=[O:14])=[CH:4][CH:3]=1.[F:24][C:25]([F:34])([F:33])[C:26]1[N:30]=[C:29]([CH2:31][NH2:32])[O:28][N:27]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][CH:19]3[CH2:23][CH2:22][O:21][CH2:20]3)=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([NH:32][CH2:31][C:29]2[O:28][N:27]=[C:26]([C:25]([F:34])([F:33])[F:24])[N:30]=2)=[O:14])=[CH:4][CH:3]=1
Reactant: NCc1nc(C(F)(F)F)no1
Reactant: O=C(O)c1cnc(OCC2CCOC2)c(-c2ccc(Cl)cc2)c1
Product: O=C(NCc1nc(C(F)(F)F)no1)c1cnc(OCC2CCOC2)c(-c2ccc(Cl)cc2)c1

Procedure:
The title compound was synthesized in analogy to Example 1 using 5-(4-chloro-phenyl)-6-(tetrahydro-furan-3-ylmethoxy)-nicotinic acid (example CK) and 3-trifluoromethyl-[1,2,4]oxadiazol-5-methanamine (example AK) as starting materials; enantiomers were separated by chiral HPLC (ChiralPak AD, 30% ethanol/n-heptane (−) enantiomer isolated; LC-MS (UV peak area/ESI) 100%, 483.1038 (M+H)+; αD20(MeOH)=−12.2°
Reaction SMILES: [CH2:1]([Si:19]([CH3:22])(Cl)Cl)[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].[OH2:23].C(N(CC)CC)C.C([O:33]CC)C>>[CH2:1]([Si:19]([CH3:22])([OH:33])[OH:23])[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[Si](C)(Cl)Cl
Reactant: O
Reactant: CCOCC
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCCC[Si](C)(O)O
Reaction time: 2 h

Procedure:
The procedure is more specifically as follows. Octadecylmethyldichlorosilane [CAS No. 5157-75-5] (1500 g, i.e. 4.08 mol) in solution in anhydrous diethyl ether (250 mL) is added dropwise (90 min) to a mixture of water (345 g), triethylamine (1138 g) and diethyl ether (29 L) kept at a temperature between −2° C. and 6° C. The mixture is then stirred for 2 h at a temperature between 0° C. and 5° C. The precipitate formed is filtered, washed successively with 6 L of demineralized water, then 3 times with 4 L of demineralized water. The solid obtained is dried in the open air until it reaches a constant mass. Octadecylmethyldihydroxysilane or octadecylmethylsilanediol (1226 g) is thus obtained in the form of a white solid having a melting point of 87° C. with a yield of 91%, NMR analysis furthermore confirming the structure of the product obtained with a molar purity of 95%.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](Cl)=[O:7].[CH2:9]([N:16]1[C:25]2[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=2)[C:19]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[C:18]([C:33]#[N:34])[C:17]1=[O:35])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>N1C=CC=CC=1>[CH2:9]([N:16]1[C:25]2[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=2)[C:19]([N:27]2[CH2:32][CH2:31][N:30]([C:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)=[O:7])[CH2:29][CH2:28]2)=[C:18]([C:33]#[N:34])[C:17]1=[O:35])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: N#Cc1c(N2CCNCC2)c2cc(Cl)ccc2n(Cc2ccccc2)c1=O
Reactant: O=C(Cl)c1cccs1
Solvent: c1ccncc1
Product: N#Cc1c(N2CCN(C(=O)c3cccs3)CC2)c2cc(Cl)ccc2n(Cc2ccccc2)c1=O
Temperature: 0 °C
Reaction time: 8 h
Yield: 81.4 %

Procedure:
2-Thiophene carbonyl chloride (160 μL, 1.5 mmol) was added to a stirred solution of Compound 71 (379 mg, 1.0 mmol) in pyridine (5 mL) under argon at 0° C. The solution was allowed to come to room temperature and further stirred overnight. The solution was poured into ice water and the solids formed were filtered. The solids were washed by excess water, dried, and recrystallized by ethyl acetate to yield 398 mg (82%) of white solids. M.P. 266° C. 1H NMR (DMSO-d6): δ 3.70 (m, 4H), 3.93 (m, 4H), 5.48 (s, 2H), 7.15 (m, 1H), 7.19-7.26 (m, 3H), 7.32 (m, 2H), 7.42 (d, J=8.9 Hz, 1H), 7.51 (d, J=4.0 Hz, 1H), 7.68 (dd, J=2.6, 8.9 Hz, 1H), 7.80 (d, J=4.0 Hz, 1H), 7.88 (s, 1H). EIMS m/z 512 (M+23). Anal. (C26H21ClN4O2S) C, H, N.
Reaction SMILES: C1(CCC(Cl)=O)CCCC1.[CH:11]1([CH2:16][CH2:17][C:18]([N:20]=[C:21]=[S:22])=[O:19])[CH2:15][CH2:14][CH2:13][CH2:12]1.[Cl:23][C:24]1[CH:30]=[C:29]([O:31][C:32]2[C:41]3[C:36](=[CH:37][C:38]([O:44][CH3:45])=[C:39]([O:42][CH3:43])[CH:40]=3)[N:35]=[CH:34][CH:33]=2)[CH:28]=[CH:27][C:25]=1[NH2:26].C1(C)C=CC=CC=1>C(O)C>[CH:11]1([CH2:16][CH2:17][C:18]([N:20]=[C:21]=[S:22])=[O:19])[CH2:12][CH2:13][CH2:14][CH2:15]1.[Cl:23][C:24]1[CH:30]=[C:29]([O:31][C:32]2[C:41]3[C:36](=[CH:37][C:38]([O:44][CH3:45])=[C:39]([O:42][CH3:43])[CH:40]=3)[N:35]=[CH:34][CH:33]=2)[CH:28]=[CH:27][C:25]=1[NH:26][C:21]([NH:20][C:18](=[O:19])[CH2:17][CH2:16][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1)=[S:22]
Reactant: COc1cc2nccc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Agent: O=C(CCC1CCCC1)N=C=S
Agent: O=C(Cl)CCC1CCCC1
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)CCC4CCCC4)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 41 %

Procedure:
3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Cyclopentylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (32 mg, yield 41%).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[CH:7][C:8]([OH:10])=O.C(N(CC)CC)C.ClC(OCC(C)C)=O.[N-:26]=[N+:27]=[N-:28].[Na+]>CC(C)=O.O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1/[CH:6]=[CH:7]/[C:8]([N:26]=[N+:27]=[N-:28])=[O:10]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(O)C=Cc1ccco1
Agent: CC(C)COC(=O)Cl
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: [N-]=[N+]=NC(=O)/C=C/c1ccco1
Temperature: -1 °C
Reaction time: 1 h

Procedure:
In an oven dried three-necked round-bottom flask (3 L) fitted with a mechanical stirrer, a nitrogen inlet, a thermometer and addition funnel was placed a mixture of β-(2-furyl)acrylic acid (60.0 g, 434 mmol) and dry triethylamine (51.6 g, 510 mmol) in acetone (600 mL, dried over anhydrous MgSO4). The mixture was cooled to −2 to 0° C. To the cold mixture, isobutyl chloroformate (79.2 g, 580 mmol) was added at 0° C. gradually over a period of time. After completion of addition, the reaction mixture was stirred at 0˜2° C. for 1 h. Then a solution of sodium azide (42.0 g, 646 mmol) in water (180 mL) was added slowly at 0˜5° C. The resulting mixture was stirred at the same temperature for 1 h. The reaction mixture was then quenched with ice-cold water (1.7 L). The desired product was extracted with toluene (4×500 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was used in next reaction as such.
Reaction SMILES: CN(OC)[C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[C:12]#[C:13][CH2:14][CH:15]([CH3:17])[CH3:16].[CH2:21]([Mg]Cl)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3](=[O:18])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:5]([C:12]#[C:13][CH2:14][CH:15]([CH3:16])[CH3:17])[CH:6]=1
Reactant: Cl[Mg]Cc1ccccc1
Reactant: COc1ccc(C(=O)N(C)OC)c(C#CCC(C)C)c1
Solvent: C1CCOC1
Product: COc1ccc(C(=O)Cc2ccccc2)c(C#CCC(C)C)c1
Yield: 91 %

Procedure:
N-Methyl-N,4-bis(methyloxy)-2-(4-methyl-1-pentyn-1-yl)benzamide (103) (0.72 g, 2.62 mmol) was treated with benzylmagnesium chloride in THF to give 0.73 g (91%) of the title compound (104) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 1.04 (d, J=6.6 Hz, 6H), 1.85-2.00 (m, 1H), 2.35 (d, J=6.6 Hz, 2H), 3.83 (s, 3H), 4.44 (s, 2H), 6.82 (dd, J1=8.8 Hz, J2=2.5 Hz, 1H), 6.98 (d, J=2.5 Hz, 1H), 7.19-7.25 (m, 3H), 7.26-7.32 (m, 2H), 7.65 (d, J=8.8 Hz, 1H). LCMS (APCI): m/z 307 (M+H)+.
Reaction SMILES: OC1C=C(C(O)CNC(C)(C)CCCC2C=C(OC)C3NC(=O)NC=3C=2)C2OCC(=O)NC=2C=1.Cl.C([O:43][C:44]1[CH:45]=[C:46]([CH:55]([OH:76])[CH2:56][NH:57][C:58]([CH3:75])([CH3:74])[CH2:59][CH2:60][CH2:61][N:62]2[C:66]3[CH:67]=[CH:68][CH:69]=[C:70]([O:71][CH3:72])[C:65]=3[NH:64][C:63]2=[O:73])[C:47]2[O:52][CH2:51][C:50](=[O:53])[NH:49][C:48]=2[CH:54]=1)C1C=CC=CC=1>CO.[Pd]>[OH:43][C:44]1[CH:45]=[C:46]([CH:55]([OH:76])[CH2:56][NH:57][C:58]([CH3:74])([CH3:75])[CH2:59][CH2:60][CH2:61][N:62]2[C:66]3[CH:67]=[CH:68][CH:69]=[C:70]([O:71][CH3:72])[C:65]=3[NH:64][C:63]2=[O:73])[C:47]2[O:52][CH2:51][C:50](=[O:53])[NH:49][C:48]=2[CH:54]=1
Reactant: COc1cccc2c1[nH]c(=O)n2CCCC(C)(C)NCC(O)c1cc(OCc2ccccc2)cc2c1OCC(=O)N2
Agent: [Pd]
Agent: COc1cc(CCCC(C)(C)NCC(O)c2cc(O)cc3c2OCC(=O)N3)cc2[nH]c(=O)[nH]c12
Agent: Cl
Solvent: CO
Product: COc1cccc2c1[nH]c(=O)n2CCCC(C)(C)NCC(O)c1cc(O)cc2c1OCC(=O)N2

Procedure:
6-hydroxy-8-{1-hydroxy-2-[4-(4-methoxy-2-oxo-2,3-dihydro-benzimidazol-6-yl)-1,1-dimethyl-butylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one: 130 mg (0.213 mmol) 6-benzyloxy-8-{1-hydroxy-2-[4-(4-methoxy-2-oxo-2,3-dihydro-benzimidazol-1-yl)-1,1-dimethyl-butylamino]-ethyl}-4H-benzo[1,4]oxazin-3-one hydrochloride are dissolved in methanol and hydrogenated at normal pressure with palladium on charcoal as catalyst. The catalyst is filtered through Celite, the filtrate is freed from the solvent and the residue is stirred with ethyl acetate. Solid. Yield: 50 mg (45%, hydrochloride); mass spectroscopy: [M+H]+=471.
Reaction SMILES: [CH:1]1([NH:4][C:5]2[C:6]([NH2:12])=[CH:7][CH:8]=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[F:13][C:14]([F:27])([F:26])[C:15]([C:18]1[CH:19]=[C:20]([CH:24]=O)[CH:21]=[N:22][CH:23]=1)([OH:17])[CH3:16].OOS([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C(OCC)(=O)C>[CH:1]1([N:4]2[C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[N:12]=[C:24]2[C:20]2[CH:19]=[C:18]([C:15]([OH:17])([CH3:16])[C:14]([F:27])([F:13])[F:26])[CH:23]=[N:22][CH:21]=2)[CH2:3][CH2:2]1
Reactant: CC(O)(c1cncc(C=O)c1)C(F)(F)F
Reactant: Nc1ccc(F)cc1NC1CC1
Agent: O=C([O-])[O-]
Agent: O=S([O-])OO
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(O)(c1cncc(-c2nc3ccc(F)cc3n2C2CC2)c1)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of the title compound from Step E (0.058 g, 0.35 mmol) in DMF (1.68 mL) and water (0.06 mL) were added the title compound from Step C (0.076 g, 0.35 mmol) and OXONE® (0.139 g, 0.226 mmol). The resulting mixture was stirred at room temperature for 1 hour, then diluted with ethyl acetate and water. Solid potassium carbonate was added until the aqueous layer was basic (pH ˜9). Ethyl acetate was then added, and the organic layer was separated, washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography on silica gel (10% acetone in dichloromethane, then 30% acetone in dichloromethane) provided the title compound as a racemic mixture. That racemic mixture was then separated into two enantiomers by HPLC (ChiralCel AS column, 25% MeOH (0.2% DEA)/CO2, 70 mL/min, 100 bar, 35° C.). Data for EXAMPLE 6 (Enantiomer A): LCMS m/z 365.99 [M+H]+; 1 H NMR (500 MHz, CDCl3) δ 9.14 (s, 1 H), 8.85 (s, 1 H), 8.59 (s, 1 H), 7.76 (dd, J=8.8, 4.8 Hz, 1 H), 7.30 (dd, J=8.5, 2.1 Hz, 1 H), 7.11-7.07 (m, 1 H), 4.85 (br s, 1 H), 3.55-3.53 (m, 1 H), 1.79 (s, 3 H), 1.22-1.12 (m, 2 H), 0.80-0.72 (m, 2 H). Data for Example 7 (Enantiomer B): LCMS m/z 365.97 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.16 (s, 1 H), 8.88 (s, 1 H), 8.57 (s, 1 H), 7.76 (dd, J=8.8, 4.8 Hz, 1 H), 7.30 (dd, J=8.5, 2.0 Hz, 1 H), 7.10-7.05 (m, 1 H), 3.91 (br s, 1 H), 3.56-3.55 (m, 1 H), 1.84 (s, 3 H), 1.18-1.15 (m, 2 H), 0.80-0.71 (m, 2 H).
Reaction SMILES: [C:1]1([CH:7]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]([CH2:26][C:27]([O:29]CC)=[O:28])[C:18]3=[O:32])[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>O>[OH2:28].[C:33]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]([CH2:26][C:27]([OH:29])=[O:28])[C:18]3=[O:32])[CH2:12][CH2:13]2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1.[C:1]1([CH:7]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]([CH2:26][C:27]([OH:29])=[O:28])[C:18]3=[O:32])[CH2:10][CH2:9]2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)Cn1c(=O)n(CCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)c2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)Cn1c(=O)n(CCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)c2ccccc21

Procedure:
A mixture of 9.8 parts of ethyl 3-{3-[4-(diphenylmethyl)-1-piperazinyl]propyl}-2,3-dihydro-2-oxo-1H-benzimidazole-1-acetate, 1.2 parts of sodium hydroxide and 150 parts of water is stirred and refluxed for 5 minutes (+80° C.). The reaction mixture is filtered and the filtrate is acidified with acetic acid to pH 5.8-6; a sticky precipitate is formed. It is separated and crystallized from ethanol and water. The product is filtered off and dried in vacuo at 100° C. for 3 hours, yielding 6 parts of 3-{3-[4-(diphenylmethyl)-1-piperazinyl]propyl}-2,3-dihydro-2-oxo-1H-benzimidazole-1-acetic acid hemihydrate; mp. 138.7° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.CC[N:21]([CH:25]([CH3:27])[CH3:26])C(C)C.[CH2:28]1COC[CH2:29]1>>[Cl:1][C:2]1[N:3]=[C:4]([NH:21][C@@H:25]([CH:26]2[CH2:29][CH2:28]2)[CH3:27])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: Fc1ccc(C2CCc3c(Cl)nc(Cl)nc32)cc1
Reactant: C1CCOC1
Product: C[C@@H](Nc1nc(Cl)nc2c1CCC2c1ccc(F)cc1)C1CC1
Temperature: 60 °C
Reaction time: 120 h
Yield: 63.1 %

Procedure:
To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation H) (100 mg, 0.353 mmol) in THF (1766 μL) was added (R)-1-cyclopropylethanamine, HCl (172 mg, 1.413 mmol) and DIEA (493 μL, 2.83 mmol). The mixture was stirred at 60° C. for 5 days. The crude product was purified by Prep-HPLC get 2-chloro-N-((R)-1-cyclopropylethyl)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (Preparation Haa) (74 mg, 0.223 mmol, 63.1% yield). LC-MS (M+H)+=332.3. 1H NMR (500 MHz, CDCl3) δ ppm 7.06-7.18 (m, 2 H) 7.00 (td, J=8.70, 1.53 Hz, 2 H) 4.65 (d, J=5.80 Hz, 1 H) 4.26 (t, J=7.17 Hz, 1 H) 3.63-3.79 (m, 1 H) 2.62-2.82 (m, 3 H) 2.04-2.16 (m, 1 H) 1.26-1.40 (m, 3 H) 0.94 (qd, J=8.24, 3.36 Hz, 1 H) 0.42-0.62 (m, 3 H) 0.24-0.40 (m, 1 H).
Reaction SMILES: [CH2:1]=[CH2:2].[C:3]1([CH3:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>>[CH2:1]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH3:9])[CH3:2]
Reactant: Cc1ccccc1
Reactant: C=C
Product: CCc1ccccc1C

Procedure:
In a manner similar to Example 1, 3.25 grams of HZSM-5 having a crystallite size of 0.02 to 0.05 micron was used. In this example, the HZSM-5 sample was mixed with 1.75 grams of alumina binder and extruded to produce a 1/16 inch cylindrical particle. The extrudate with a volume of 9 ml. was diluted with 4 volumes of low surface area quartz and tested for ability to alkylate toluene with ethylene to yield ethyltoluene. The conditions of reaction and results are shown in Table II below.
Reaction SMILES: [C:1]1([N:7]2[C:11]([S:12][C:13]3[C:14](=[O:28])[C:15]([C:20]([CH3:27])([CH3:26])[CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:16][C:17](=[O:19])[CH:18]=3)=[N:10][N:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:29]1([SH:35])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CO>[C:1]1([N:7]2[C:11]([S:12][C:13]3[C:18]([S:35][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:17]([OH:19])[CH:16]=[C:15]([C:20]([CH3:27])([CH3:26])[CH2:21][C:22]([CH3:23])([CH3:25])[CH3:24])[C:14]=3[OH:28])=[N:10][N:9]=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Sc1ccccc1
Reactant: CC(C)(C)CC(C)(C)C1=CC(=O)C=C(Sc2nnnn2-c2ccccc2)C1=O
Solvent: CO
Product: CC(C)(C)CC(C)(C)c1cc(O)c(Sc2ccccc2)c(Sc2nnnn2-c2ccccc2)c1O
Temperature: 0 °C

Procedure:
15g of 2-(1-phenyl-5-tetrazolylthio)-6-(1,1,3,3-tetramethylbutyl)-p-benzoquinone was added to 150ml of methanol and the mixture was cooled to 0°C while stirring. Then a solution of 4.5g of thiophenol in 25ml of methanol was added dropwise to this mixture. After the addition, the mixture was stirred at 0°C for 3 hours. The resulting crystals were separated by filtration and recrystallized from a solvent mixture of n-hexane and ethyl acetate (n-hexane/ethyl acetate = 5/1 by volume). Thus 7.5g of 2-(1-phenyl-5-tetrazolylthio)-3-phenylthio-6-(1,1,3,3-tetramethylbutyl)-hydroquinone having a melting point of 147°C was obtained.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)=[CH:6][C:3]=1[CH:4]=O.[NH2:17][C:18]1[C:25]([F:26])=[CH:24][CH:23]=[C:22]([O:27][CH3:28])[C:19]=1[C:20]#[N:21].[BH4-].[Na+]>C1(C)C=CC=CC=1.CO>[F:26][C:25]1[C:18]([NH:17][CH2:4][C:3]2[CH:6]=[C:7]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=3)[CH:8]=[CH:9][C:2]=2[F:1])=[C:19]([C:22]([O:27][CH3:28])=[CH:23][CH:24]=1)[C:20]#[N:21]
Reactant: COc1ccc(F)c(N)c1C#N
Reactant: O=Cc1cc(-c2cccc(F)c2)ccc1F
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Product: COc1ccc(F)c(NCc2cc(-c3cccc(F)c3)ccc2F)c1C#N
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.8 %

Procedure:
To a solution of 2-fluoro-5-(3-fluorophenyl)benzaldehyde (505 mg, 2.32 mmol, 1.2 eq) and 2-amino-3-fluoro-6-methoxy-benzonitrile (320 mg, 1.93 mmol, 1 eq) in toluene (30 mL) was added 4 Å molecular sieves (10 g). The mixture was heated at reflux for 4 h, then filtered to remove the molecular sieves. The filtrate was concentrated and the residue obtained was dissolved in methanol (30 mL). NaBH4 (109.6 mg, 2.9 mmol, 1.5 eq) was added and the reaction stirred for 2 h at room temperature. The reaction was quenched by addition of water, and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 50:1) to give the title compound as an off-white solid (610 mg, 72%).
Reaction SMILES: [C:1]([O:4][C@H:5]([CH3:11])[CH2:6][CH2:7][CH2:8][CH2:9]Cl)(=[O:3])[CH3:2].[I-:12].[Na+]>>[C:1]([O:4][C@H:5]([CH3:11])[CH2:6][CH2:7][CH2:8][CH2:9][I:12])(=[O:3])[CH3:2]
Reactant: [I-]
Reactant: CC(=O)O[C@H](C)CCCCCl
Agent: [Na+]
Product: CC(=O)O[C@H](C)CCCCI

Procedure:
First, (R)-5-acetoxy-1-iodohexane was prepared in the following manner. A solution of (R)-5-acetoxy-1-chlorohexane (4.80 g:26.89 mmol) was added to sodium iodide (5.39 g:36 mmol) in a round bottomed flask fitted with magnetic stirrer bar and a reflux condenser and refluxed for 12 hrs with stirring. Acetone was removed under reduced pressure, The crude product was partitioned between ethyl acetate (50 ml) and water layer (60 ml). The organic layer was washed with 10% sodium thiosulphate solution followed by water (20 l), dried over anhydrous Mg SO4 and concentrated under reduced pressure. Yield=7 g (96%)
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][C:8]([SH:11])=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].CN(C=O)C.[H-].[Na+].Cl[CH2:20][O:21][CH2:22][CH3:23]>O>[N+:1]([C:4]1[CH:10]=[CH:9][C:8]([S:11][CH2:20][O:21][CH2:22][CH3:23])=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2]
Reactant: Nc1cc(S)ccc1[N+](=O)[O-]
Reactant: CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOCSc1ccc([N+](=O)[O-])c(N)c1
Reaction time: 0.5 h

Procedure:
A solution of 3.4 g. of 2-nitro-5-mercaptoaniline in 20 ml. of DMF is treated with 0.5 g. of 100% sodium hydride, and 2.2 g. of chloromethyl-ethyl ether is added to the solution. After 30 minutes at 20°-25° C, the solution is diluted with water and extracted with chloroform. Removal of the chloroform leaves 2-nitro-5-(ethoxymethylthio) aniline as an oil.
Reaction SMILES: [CH3:1][C:2]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[N+:12]([O-])=O)=[O:3].[CH:15]([Mg]Br)=[CH2:16]>C1COCC1>[F:11][C:8]1[CH:9]=[CH:10][C:5]([NH:4][C:2](=[O:3])[CH3:1])=[C:6]2[C:7]=1[CH:15]=[CH:16][NH:12]2
Reactant: C=C[Mg]Br
Reactant: CC(=O)Nc1ccc(F)cc1[N+](=O)[O-]
Solvent: C1CCOC1
Product: CC(=O)Nc1ccc(F)c2cc[nH]c12
Temperature: -78 °C
Reaction time: 2 h

Procedure:
4-Fluoro-2-nitroacetanilide (1 eq.) was dissolved in dry THF. After the solution was cooled down to −78° C., an excess of vinyl magnesium bromide (3-4 eq.) was added. Then, the reaction was kept below −40° C. for two hours before quenched with 20% NH4Cl. The aqueous phase was extracted with EtOAc. The combined organic layer was dried over MgSO4. After filtration and concentration, the crude product was purified by silica gel column chromatography to afford N-(4-fluoro-1H-indol-7-yl)acetamide. MS m/z: (M+H)+ calc'd for C10H10FN2O: 193.08. Found 193.09. HPLC retention time: 1.29 minutes (column E, solvent system II).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:9])[CH2:4][C:5]([CH2:7][Cl:8])=[O:6].[CH:10](=O)[CH2:11][CH3:12].C(O)(=O)C>ClCCl.N1CCCCC1>[CH3:1][O:2][C:3](=[O:9])[C:4](=[CH:10][CH2:11][CH3:12])[C:5]([CH2:7][Cl:8])=[O:6]
Reactant: CCC=O
Reactant: COC(=O)CC(=O)CCl
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: C1CCNCC1
Product: CCC=C(C(=O)CCl)C(=O)OC
Temperature: -27 °C
Reaction time: 2 h
Yield: 92.3 %

Procedure:
To a solution of 4-chloroacetoacetic acid methyl ester (700 mg: 4.65 mMol.) and propionaldehyde (405 mg: 6.97 mMol.) and acetic acid (28 mg: 0.47 mMol.) in dichloromethane (3 ml) is added a solution of piperidine (24 mg: 0.28 mMol.) in dichloromethane (0.5 ml), and the mixture is stirred at -27° C. for 120 minutes. The reaction mixture is washed with dilute hydrochloric acid and water and concentrated under reduced pressure at lower than 15° C. to give 4-chloro-2-propylideneacetoacetic acid methyl ester (818 mg). Yield: 92%.