Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:4]2[CH2:5][CH2:6][C:3]=12.C(N(CC)CC)C.Cl[Si:18]([CH3:21])([CH3:20])[CH3:19]>C1C=CC=CC=1>[CH3:19][Si:18]([CH3:21])([CH3:20])[O:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:4]2[CH2:5][CH2:6][C:3]=12
Reactant: Oc1cccc2c1CC2
Reactant: C[Si](C)(C)Cl
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)Oc1cccc2c1CC2
Temperature: 5 °C
Reaction time: 8 h
Yield: 76 %

Procedure:
A larger batch of 4-trimethylsiloxybenzocyclobutene was synthesized from 6.56 gms of 4-hydroxybenzocyclobutene and 5.54 gms of triethylamine, taken up in 15 ml anhydrous benzene followed by the addition of a nearly three molar excess of chlorotrimethylsilane (20 ml in 15 ml dry benzene) to the reaction mixture maintained at 5° C. An instant white precipitation of triethylamine hydrochloride was observed. The solution was allowed to warm up on its own to 15° C. in about 5 hours and the reaction mixture was kept stirred overnight, It was warmed to 40° C. and maintained for about three hours. The reaction mixture was cooled and the isolation of the product was done exactly as described before. The weight of the light yellow oil (crude) was 7.93 g, 76% yield. Total amount of the colorless oil obtained from vacuum distillation was 7.07 grams. Anal. Calc.: C, 68.69%; H, 8.38%. Found: C, 69.15%; H, 8.44%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:19][CH:20]3[CH2:37][CH:36]4[N:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39](O)=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)=[N:8][C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:10]2)=[CH:5][C:4]=1[CH3:44].[CH:45]1([S:48]([NH2:51])(=[O:50])=[O:49])[CH2:47][CH2:46]1>>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:19][CH:20]3[CH2:37][CH:36]4[N:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39]([NH:51][S:48]([CH:45]6[CH2:47][CH2:46]6)(=[O:50])=[O:49])=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)=[N:8][C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:10]2)=[CH:5][C:4]=1[CH3:44]
Reactant: NS(=O)(=O)C1CC1
Reactant: COc1cc2nc(-c3ccccc3)nc(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCN(C)C(=O)N4C3)c2cc1C
Product: COc1cc2nc(-c3ccccc3)nc(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)N4C3)c2cc1C
Yield: 19 %

Procedure:
Reaction of the acid 120 (36 mg, 0.06 mmol) with cyclopropanesulfonic acid amide according to the procedure described in Example 53, gave the title compound (8 mg, 19%). MS (M−H)+ 703.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][N:3]=1.[CH2:10]([NH2:13])[CH2:11][NH2:12]>>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:8][NH:12][CH2:11][CH2:10][NH2:13])=[CH:6][CH:7]=1
Reactant: NCCN
Reactant: ClCc1ccc(Cl)nc1
Product: NCCNCc1ccc(Cl)nc1
Reaction time: 8 h
Yield: 100 %

Procedure:
Next, 20 mL of ethylenediamine was added to 2.0 g (12.4 mmol) of 2-chloro-5-chloromethylpyridine, and the mixture was stirred overnight. Following reaction completion, the reaction mixture was concentrated under reduced pressure, after which acetonitrile was added and insoluble matter were removed by filtration. The filtrate was concentrated under reduced pressure, giving 2.45 g (yield, 100%) of N-((6-chloropyridin-3-yl)methyl)ethane-1,2-diamine.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([F:12])=[C:8]([CH:11]=1)[C:9]#[N:10])([O-])=O.[NH4+].[Cl-]>CCO.O.[Fe]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([F:12])=[C:8]([CH:11]=1)[C:9]#[N:10]
Reactant: N#Cc1cc([N+](=O)[O-])ccc1F
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: N#Cc1cc(N)ccc1F
Yield: 61 %

Procedure:
A mixture of 5-nitro-2-fluorobenzonitrile (10 g, 60.2 mmol), Fe powder (17 g, 0.3 mol), and NH4Cl (1.7 g, 30 mmol) in EtOH/H2O (100 mL, 9:1) was heated at reflux in 2 h. The mixture was filtered at hot. The filtrate was concentrated, taken up in H2O, stirred, filtered air-dried to obtain the title solid as a tan solid, (5.0 g, 71%). 1H NMR (400 MHz, DMSO-d6): d 5.54 (s, 2H), 6.85 (m, 2H), 7.16 (t, J=8.1 Hz, 1H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][OH:6].[OH-].[K+].S(O[CH:20]([CH2:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:21])(C1C=CC(C)=CC=1)(=O)=O.O>O1CCOCC1>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH:20]([CH2:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:21]
Reactant: OCCCCO
Reactant: Cc1ccc(S(=O)(=O)OC(C)COCc2ccccc2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CC(COCc1ccccc1)OCCCCO
Temperature: 102 °C
Reaction time: 4 h
Yield: 58.3 %

Procedure:
HO(CH2)4OH (37 g), potassium hydroxide (23 g) and dioxane (200 ml) were charged into a four necked flask and heated to an internal temperature of 102° C. to dissolve potassium hydroxide. A solution of TsOCH(CH3)CH2OCH2Ph (63.7 g) obtained in Example 2-1 in dioxane (65 ml), was dropwise added over a period of 1 hour and stirred for 4 hours. The mixture was left to cool, then added to water (350 ml) and extracted three times with dichloromethane (100 ml). The organic layer was washed with water (20 ml). It was dried over magnesium sulfate, filtered and then concentrated by an evaporator to obtain a crude product (52 g). It was purified by silica gel column chromatography to obtain the above-identified compound (27.6 g).
Reaction SMILES: [SH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[C:7](=[O:13])[CH2:6][CH2:5]2.[CH2:14]([CH:16]1[CH2:21][C:20]([OH:29])([C:22]2[CH:27]=[CH:26][CH:25]=[C:24](I)[CH:23]=2)[CH2:19][CH2:18][O:17]1)[CH3:15]>>[CH2:14]([CH:16]1[CH2:21][C:20]([OH:29])([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([S:1][C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[N:8]([CH3:12])[C:7](=[O:13])[CH2:6][CH2:5]4)[CH:23]=2)[CH2:19][CH2:18][O:17]1)[CH3:15]
Reactant: CCC1CC(O)(c2cccc(I)c2)CCO1
Reactant: CN1C(=O)CCc2cc(S)ccc21
Product: CCC1CC(O)(c2cccc(Sc3ccc4c(c3)CCC(=O)N4C)c2)CCO1
Yield: 63 %

Procedure:
Using an analogous procedure to that described in Example 6, 6-mercapto-1-methyl-1,2,3,4-tetrahydroquinolin-2-one was reacted with (2SR,4RS)-2-ethyl-4-hydroxy-4-(3-iodophenyl)tetrahydropyran to give (2SR,4RS)-2-ethyl-4-hydroxy-4-[3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylthio)phenyl]tetrahydropyran in 63% yield as a gum;
Reaction SMILES: Cl[CH:2]([CH3:4])[CH3:3].[CH3:5][NH:6][C:7](=[O:25])/[C:8](/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[N:9]/[O:10][CH3:11]>>[CH3:5][NH:6][C:7](=[O:25])/[C:8](/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][C:19]1[CH:20]=[CH:21][C:22]([CH:2]([CH3:4])[CH3:3])=[CH:23][CH:24]=1)=[N:9]/[O:10][CH3:11]
Reactant: CNC(=O)/C(=N/OC)c1ccccc1Oc1ccccc1
Reactant: CC(C)Cl
Product: CNC(=O)/C(=N/OC)c1ccccc1Oc1ccc(C(C)C)cc1

Procedure:
In the same manner as in Example 14, the objective compound was prepared from 2-chloropropane and (E)-N-methyl-2-(2-phenoxyphenyl)-2-methoxyiminoacetamide.
Reaction SMILES: [CH:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1)=[CH2:2].[CH2:11](O)[CH2:12][OH:13].C1(C)C=CC=CC=1>C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]2[O:13][CH2:12][CH2:11][O:8]2)=[CH:5][CH:4]=1)=[CH2:2]
Reactant: C=Cc1ccc(C=O)cc1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: C=Cc1ccc(C2OCCO2)cc1
Temperature: 45 °C
Yield: 96.3 %

Procedure:
In a 250 ml 3-necked round-bottomed flask, 13.72 g of (103 mmol) of 4-vinylbenzaldehyde, 7.08 g (114 mmol) of ethylene glycol and 0.23 g (1.3 mmol) of p-toluenesulfonic acid are added to 100 ml of toluene. The resulting mixture is refluxed at 45° C. under reduced pressure for 3 hours using a water separator. It is then washed twice with 100 ml of water, and the organic phase is dried over magnesium sulfate and concentrated to yield 17.47 g of crude product in the form of a pale yellow oil. The latter is distilled at 80° C./0.05 mbar. Yield: 12.81 g (72.7 mmol, 70.6% of the theoretical yield). 1H-NMR (CDCl3, 100 mHz): δ7.39/s/4H, 6.68/dd (J1 =11 Hz, J2 =18 Hz)/1H, 5.74/s/1H, 5.72 (J1 =18 Hz, J2 =2 Hz)/1H, 5.22/dd (J1 =11 Hz, J2 =2 Hz)/1H, 3.96/m/4H.
Reaction SMILES: [CH3:1][N:2]1[C:6]([NH2:7])=[CH:5][C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[N:3]1.[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[C:17]([CH3:23])[CH:16]=1.O.CC1C=CC(S(O)(=O)=O)=CC=1>CC#N>[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[C:5]2[C:6](=[NH:7])[N:2]([CH3:1])[N:3]=[C:4]2[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[C:17]([CH3:23])[CH:16]=1
Reactant: Cn1nc(-c2ccccn2)cc1N
Reactant: Cc1cc(Br)ccc1C=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CC#N
Product: Cc1cc(Br)ccc1C=C1C(=N)N(C)N=C1c1ccccn1
Temperature: 45 °C
Yield: 64.1 %

Procedure:
A suspension of 1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5-amine (4.50 g, 25.8 mmol, Example #2 step B), 4-bromo-2-methylbenzaldehyde (5.14 g, 25.8 mmol, Astatech) and 4-methylbenzenesulfonic acid hydrate (0.491 g, 2.58 mmol) in MeCN (36 ml) was warmed up to about 45° C. for about 15 min to give a solution then the reaction was allowed to cool to rt. The precipitate was filtered and washed with MeCN to give 4-(4-bromo-2-methylbenzylidene)-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5(4H)-imine (5.88 g, 16.55 mmol, 64%) as a beige solid: LC-MS (Table 1, Method g) Rt=2.55 min, m/z 355/357 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 9.07 (s, 1H), 8.60-8.57 (m, 1H), 8.02-7.95 (m, 2H), 7.91-7.86 (m, 1H), 7.61-7.50 (m, 2H), 7.40-7.31 (m, 1H), 7.19 (s, 1H), 3.96 (s, 3H), 2.62 (s, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:36])[O:5][C:6]1[C:17]2[C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:14](=[O:27])[C:13]=2[C:12]([OH:28])=[C:11]2[C:7]=1[N:8]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:9]=[N:10]2)[CH3:2].[C:37]1([C:43]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[N+]=[N-])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>ClCCCl>[CH2:1]([O:3][C:4](=[O:36])[O:5][C:6]1[C:17]2[C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)[C:14](=[O:27])[C:13]=2[C:12]([O:28][CH:43]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[C:11]2[C:7]=1[N:8]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH:9]=[N:10]2)[CH3:2]
Reactant: [N-]=[N+]=C(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)Oc1c2c(c(O)c3ncn(Cc4ccccc4)c13)C(=O)N(Cc1ccc(F)cc1)C2=O
Solvent: ClCCCl
Product: CCOC(=O)Oc1c2c(c(OC(c3ccccc3)c3ccccc3)c3ncn(Cc4ccccc4)c13)C(=O)N(Cc1ccc(F)cc1)C2=O
Temperature: 70 °C
Yield: 78.6 %

Procedure:
Carbonic acid 3-benzyl-6-(4-fluoro-benzyl)-8-hydroxy-5,7-dioxo-3,5,6,7-tetrahydro-1,3,6-triaza-s-indacen-4-yl ester ethyl ester 256 (140 mg, 0.28 mmol, 1 equiv.) was dissolved in 1,2 dichloroethane (20 mL) and to this was added diphenyldiazomethane (72 mg, 0.37 mmol, 1.3 equiv.) and heated at 70° C. under a nitrogen atmosphere for 24 hours. The reaction was then concentrated in vacuo and purified by silica gel chromatography using 7/3 Hexanes/Ethyl acetate to obtain carbonic acid 8-benzhydryloxy-3-benzyl-6-(4-fluoro-benzyl)-5,7-dioxo-3,5,6,7-tetrahydro-1,3,6-triaza-s-indacen-4-yl ester ethyl ester 257 (78%, 135 mg, 0.22 mmol). 1H NMR (300 MHz) CDCl3 δ 8.17 (s, 1 H), 7.91 (s, 1 H), 7.68 (d, J=7.2 Hz, 4 H), 7.21-7.42 (m, 12 H), 6.95-7.06 (s, 4 H), 5.49 (s, 2 H), 4.76 (s, 2 H), 4.11 (q, J=6.9 Hz, 2 H), 1.17 (t, J=6.9 Hz, 3 H). MS: 678.1 (M+23). TLC Rf: 0.3 Hexanes/Ethyl acetate (7/3)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH2:10][C:11]([OH:13])=[O:12].OS(O)(=O)=O.[CH3:19]O>>[CH3:19][O:12][C:11](=[O:13])[CH2:10][C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[Cl:1]
Reactant: CO
Reactant: COc1ccc(Cl)c(CC(=O)O)c1
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1cc(OC)ccc1Cl

Procedure:
2-Chloro-5-methoxy-benzeneacetic acid (10 g, CAS Reg. No. 91367-10-1) was dissolved in MeOH (210 mL) and H2SO4 (0.7 mL) was added. The mixture was then refluxed over night. Methanol was removed in vacuo and the residue was dissolved in ethyl acetate. The organic layer was washed with sat. NaHCO3 and brine, dried over Na2SO4 and evaporated. The title compound was obtained as a light brown oil (10.16 g) and was used without further purification. 1H-NMR (□, CDCl3): 7.27 (d, 1H), 6.83 (d, 1H), 6.77 (dd, 1H), 3.79 (s, 3H), 3.74 (s, 2H), 3.72 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([C@@H:12](O)[CH3:13])[CH2:11][O:10]1.[F:15][C:16]([F:32])([F:31])[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[NH:28][CH:27]=[N:26]2)=[CH:21][CH:20]=1>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([O:10][CH2:11]1)[C@H:12]([N:28]1[CH:27]=[N:26][N:25]([C:22]2[CH:23]=[CH:24][C:19]([O:18][CH2:17][C:16]([F:31])([F:32])[F:15])=[CH:20][CH:21]=2)[C:29]1=[O:30])[CH3:13]
Reactant: C[C@H](O)[C@@]1(c2ccc(F)cc2F)CO1
Reactant: O=c1[nH]cnn1-c1ccc(OCC(F)(F)F)cc1
Product: C[C@@H](n1cnn(-c2ccc(OCC(F)(F)F)cc2)c1=O)[C@@]1(c2ccc(F)cc2F)CO1
Yield: 48.4 %

Procedure:
In the same manner as in Reference Example 5, starting from 0.971 g of (1S)-[(2R)-(2,4-difluorophenyl)-2-oxiranyl]ethanol and 1.0 g of 2-[4-(2,2,2-trifluoroethoxy) phenyl]-3(2H,4H)-1,2,4-triazolone, 0.825 g of 4-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-epoxy-1-methylpropyl]-2-[4-(2,2,2-trifluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone was obtained as colorless prisms.
Reaction SMILES: [Cl:1][CH:2]([P:17](=[O:30])([O:24][CH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[O:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)[P:3](=[O:16])([O:10][CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)[O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[Cl-].[Br:32][O-].[Na+]>C(Cl)(Cl)(Cl)Cl>[Br:32][C:2]([Cl:1])([P:3](=[O:16])([O:10][CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)[O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)[P:17](=[O:30])([O:24][CH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[O:18][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: [O-]Br
Reactant: O=P(OC1CCCC1)(OC1CCCC1)C(Cl)P(=O)(OC1CCCC1)OC1CCCC1
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: O=P(OC1CCCC1)(OC1CCCC1)C(Cl)(Br)P(=O)(OC1CCCC1)OC1CCCC1
Temperature: 10 °C

Procedure:
4.8 g (0.01 moles) of tetracyclopentyl (monochloromethylene)bisphosphonate (31P-NMR (CDCl3): δ 12.44 ppm, 2JPH =17.7 Hz) are dissolved in 20 ml of carbontetrachloride and 0.55 g of bensyltriethylammonium chloride and 20 ml of a 10% sodium hypobromite solution are added while cooling and stirring at about 10° C. The mixture is stirred vigorously for 30 min at about 10° C. and the organic phase is separated, washed with water, dried (Na2SO4) and filtered. The filtrate is evaporated in a vacuum, whereby about 5.0 g (90% of the theor.) of tetracyclopentyl (bromochloromethylene)bisphosphonate (31P-NMR (CDCl3): δ 7.68 ppm) is obtained as a colourless oil at a concentration of >80%.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](Cl)=[N:7][OH:8])=[CH:4][CH:3]=1.[CH3:12][CH2:13][O:14][C:15](/[CH:17]=[C:18](/N1CCCC1)\[CH3:19])=[O:16].C(N(CC)CC)C>C(O)C>[CH2:13]([O:14][C:15]([C:17]1[C:6]([C:5]2[CH:10]=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=2)=[N:7][O:8][C:18]=1[CH3:19])=[O:16])[CH3:12]
Reactant: ON=C(Cl)c1ccc(Cl)cc1
Reactant: CCOC(=O)/C=C(\C)N1CCCC1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1c(-c2ccc(Cl)cc2)noc1C
Yield: 69.8 %

Procedure:
To a suspension of 4-chloro-N-hydroxy-benzimidoyl chloride (1.11 g, 5.88 mmol) in dry ethanol (9 ml) was added a solution of ethyl (E)-3-(1-pyrrolidino)crotonate (1.08 g, 5.88 mmol) and triethylamine (492 μl, 3.53 mmol) in dry ethanol (9 ml) over a period of twenty minutes at room temperature. The suspension was stirred for eighteen hours before the mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic layer was washed with 0.5 N HCl and brine, before it was dried and concentrated in vacuo. The residue was purified by flash column chromatography with a gradient of ethyl acetate and hexanes on silica gel (40 g) to give the title compound as a white solid (1.09 g): 1H NMR (CDCl3, 200 MHz): δ=7.57 (m, 2H), 7.42 (m, 2H), 4.25 (q, J=7.0 Hz, 2H), 2.74 (s, 3H), 1.27 (t, J=7.0 Hz, 3H); MS: (+) m/z 266.31 (M+1).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[F:11][C:12]([F:26])([F:25])[C:13]([NH:15][C:16]1[CH:21]=[C:20]([NH:22][CH3:23])[CH:19]=[CH:18][C:17]=1[F:24])=[O:14]>CN(C)C=O.C(OCC)(=O)C>[F:26][C:12]([F:11])([F:25])[C:13]([NH:15][C:16]1[CH:21]=[C:20]([N:22]([CH3:23])[C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=2)[CH:19]=[CH:18][C:17]=1[F:24])=[O:14]
Reactant: CNc1ccc(F)c(NC(=O)C(F)(F)F)c1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN(c1ccc(F)c(NC(=O)C(F)(F)F)c1)c1ccc([N+](=O)[O-])cn1
Temperature: 25 °C
Yield: 48.6 %

Procedure:
A solution of 2-chloro-5-nitropyridine (201 mg, 1.27 mmol) and 2,2,2-trifluoro-N-[2-fluoro-5-(methylamino)phenyl]acetamide (300 mg, 1.27 mmol) in N,N-dimethylformamide (1.5 mL) was stirred at 140° C. for 22 hr. The reaction mixture was cooled to room temperature, and suspended in ethyl acetate (5 mL), and the suspension was washed with saturated aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure, and the obtained residue was crystallized from ethyl acetate/hexane to give the title compound (221 mg, 49%) as yellow crystals.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[O:10][C:9](=[O:11])[NH:8][C:5]2=[N:6][CH:7]=1.[Li]N([Si](C)(C)C)[Si](C)(C)[CH3:15].COS(OC)(=O)=O>C1COCC1>[CH3:15][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=[C:4]2[O:10][C:9]1=[O:11]
Reactant: O=c1[nH]c2ncc(Br)cc2o1
Reactant: [Li]N([Si](C)(C)C)[Si](C)(C)C
Solvent: C1CCOC1
Solvent: COS(=O)(=O)OC
Product: Cn1c(=O)oc2cc(Br)cnc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 4.7 g of 6-bromo-oxazolo[4,5-b]pyridin-2(3H)-one (0.022 mole) in 90 ml of THF is added 24 ml of LiN(TMS)2 (0.024 mole) in THF. The homogenous solution is maintained under nitrogen at room temperature for 20 min., 3.03 g (0.024 mole) of dimethylsulfate is added and the reaction mixture allowed to stir overnight. The reaction mixture is then quenched with 20 ml of sat. ammonium chloride and extracted with 3×80 ml ethyl acetate. The ethyl acetate is then washed with 3×30 ml sat. ammonium chloride, dried over sodium sulfate and concentrated to obtain off white product which is used directly in the next step.
Reaction SMILES: [O:1]=[C:2]1[N:6]2[CH2:7][C:8](=[O:14])[NH:9][C:10]3[CH:11]=[CH:12][CH:13]=[C:4]([C:5]=32)[N:3]1[CH2:15][C:16]([O:18]C)=[O:17].[OH-].[Na+:21].Cl>CO.CC#N>[O:1]=[C:2]1[N:6]2[CH2:7][C:8](=[O:14])[NH:9][C:10]3[CH:11]=[CH:12][CH:13]=[C:4]([C:5]=32)[N:3]1[CH2:15][C:16]([O-:18])=[O:17].[Na+:21]
Reactant: COC(=O)Cn1c(=O)n2c3c(cccc31)NC(=O)C2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC#N
Product: O=C([O-])Cn1c(=O)n2c3c(cccc31)NC(=O)C2
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of methyl (2,5-dioxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxalin-1(2H)-yl) acetate from Step C (367 mg, 1.40 mmol) in MeOH (40 mL) and CH3CN (5 mL) was added 1.0 N sodium hydroxide (2.82 mL, 2.82 mmol) and the reaction mixture was stirred at room temperature for 18 h. The mixture was neutralized with 1 N aqueous HCl and concentrated in vacuo to give the title compound. MS: m/z=248 (M+1).
Reaction SMILES: [Cl:1][SiH:2]([Cl:4])[Cl:3].[CH:5]1[CH2:9][CH2:8][CH2:7][CH:6]=1>[Pt]>[CH:5]1([Si:2]([Cl:4])([Cl:3])[Cl:1])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: C1=CCCC1
Reactant: Cl[SiH](Cl)Cl
Agent: [Pt]
Agent: *C(F)(F)C(*)(F)F
Product: Cl[Si](Cl)(Cl)C1CCCC1
Yield: 91 %

Procedure:
The experiment was conducted in substantially the same manner as in Example 1 by preparing a reaction mixture from 19.5 g (0.144 mole) of trichlorosilane, 9.9 g (0.146 mole) of cyclopentene and 0.14 g of the catalyst I corresponding to 238 ppm by weight as platinum based on the total amount of trichlorosilane and cyclopentene and heating the mixture in a polytetrafluoroethylene-made pressure-resistant vessel at 60° C. for 26 hours under a spontaneously produced pressure of 3 kg/cm2G. About 97% of the starting reactants had been reacted at the end of the reaction time as determined by the gas chromatographic analysis. Treatment of the reaction mixture after the reaction was performed in the same manner as in Example 1 to give cyclopentyl trichlorosilane in a yield of 91% as isolated based on the theoretical value.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:15]3[C:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)=[C:9]([C:16]#[N:17])[CH:8]=2)=[CH:3][CH:2]=1.[Br:18]N1C(=O)CCC1=O>>[Br:18][C:8]1[C:9]([C:16]#[N:17])=[C:10]2[N:15]([C:7]=1[C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)[CH2:14][CH2:13][CH2:12][CH2:11]2
Reactant: N#Cc1cc(-c2ccncc2)n2c1CCCC2
Reactant: O=C1CCC(=O)N1Br
Product: N#Cc1c(Br)c(-c2ccncc2)n2c1CCCC2
Yield: 84 %

Procedure:
2-Bromo-3-(4-pyridyl)-5,6,7,8-tetrahydroindolizine-1-carbonitrile is prepared as described in Example 9, from 2.2 g [lacuna] 3-(4-pyridyl)-5,6,7,8-tetrahydroindolizine-1-carbonitrile and 2.26 g of N-bromosuccinimide. 2.5 g of 2-bromo-3-(4-pyridyl)-5,6,7,8-tetrahydroindolizine-1-carbonitrile are thus obtained in the form of orange-beige powder melting at 120° C.
Reaction SMILES: [C:1]1([C:7]2[N:16]=[C:15]([C:17]([O:19]CC)=O)[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][NH:24]1.C([Li])CCC>CCCCCC.O1CCCC1>[CH3:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]1[C:17]([C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:16]=1)=[O:19]
Reactant: CCOC(=O)c1nc(-c2ccccc2)nc2ccccc12
Reactant: CC1CCCCN1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC1CCCCN1C(=O)c1nc(-c2ccccc2)nc2ccccc12

Procedure:
The procedure of Example 24 is followed using ethyl 2-phenylquinazoline-4-carboxylate (3 g), 2-methylpiperidine (3 ml), a 1.6M solution of butyllithium in hexane (15 ml) and tetrahydrofuran (20 ml) as the starting materials. After recrystallisation from ethanol, 2-methyl-1-[(2-phenylquinazolin-4-yl)-carbonyl]-piperidine (1.7 g), melting at 150° C., is obtained.
Reaction SMILES: Br.[CH3:2][S:3]([C:6]1[CH:7]=[C:8]([C:12]2[S:16][C:15]([NH2:17])=[N:14][C:13]=2[CH3:18])[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4].CCN(C(C)C)C(C)C.[CH2:28]([O:30][C:31](=[O:37])[CH2:32][CH2:33][N:34]=[C:35]=[O:36])[CH3:29]>C(Cl)Cl>[CH2:28]([O:30][C:31](=[O:37])[CH2:32][CH2:33][NH:34][C:35]([NH:17][C:15]1[S:16][C:12]([C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([S:3]([CH3:2])(=[O:4])=[O:5])[CH:7]=2)=[C:13]([CH3:18])[N:14]=1)=[O:36])[CH3:29]
Reactant: Cc1nc(N)sc1-c1cccc(S(C)(=O)=O)c1
Reactant: CCOC(=O)CCN=C=O
Agent: Br
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCNC(=O)Nc1nc(C)c(-c2cccc(S(C)(=O)=O)c2)s1
Temperature: 60 °C

Procedure:
A stirred suspension of 5-(3-methanesulphonyl-phenyl)-4-methyl-thiazol-2-ylamine hydrobromide (176d) (0.172 g, 0.64 mmol) in DCM (15 ml) is treated with Hunigs base (0.45 ml, 2.36 mmol) followed by ethyl-3-isocyanatopropionate (0.092 g, 0.64 mmol). The reaction mixture is stirred and heated to 60° C. for 10 hours and then the solvent in removed in vacuo. The product is purified by chromatography on silica to give the titled compound