Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.O1CCCCC1[O:8][CH2:9][CH2:10][C:11]1([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]1>CCOCC.CO.C(OC(C)C)(C)C.CCOCC>[OH:8][CH2:9][CH2:10][C:11]1([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]1
Reactant: Clc1ccc(C2(CCOC3CCCCO3)CCCNC2)cc1Cl
Agent: Cl
Solvent: CO
Solvent: CCOCC
Solvent: CC(C)OC(C)C
Product: OCCC1(c2ccc(Cl)c(Cl)c2)CCCNC1
Temperature: 25 °C
Yield: 106.9 %

Procedure:
A saturated solution of hydrogen chloride in ether is added to a solution of 55 g of 3-(2-tetrahydropyranyloxyethyl)-3-(3,4-dichlorophenyl)piperidine in 200 ml of methanol until the pH is 1. The mixture is stirred for half an hour at room temperature and concentrated to dryness, the residue is taken up in water, rendered alkaline with a solution of NaOH and extracted with CH2Cl2 and the extract is washed with a saturated solution of NaCl, dried over Na2SO4 and evaporated to dryness to give an oil. This oil is taken up in 200 ml of an isopropyl ether/ether mixture (50/50 v/v). After stirring and filtration, the product is washed with ethyl ether and dried under vacuum over P2O5 to give 45 g of the expected product. M.p.=122° C.
Reaction SMILES: F[C:2](F)(F)[C:3](O)=O.[CH:8]1[C:16]2[C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[O:13][C:12]=2[C:11]([C:21]2[N:26]=[C:25](NC3C=CC=C(N)C=3)[N:24]=[CH:23][CH:22]=2)=[CH:10][CH:9]=1.Cl.[CH3:36][N:37]([CH3:47])[C:38]1[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=1)[C:41](Cl)=[O:42]>N1C=CC=CC=1>[CH:8]1[C:16]2[C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[O:13][C:12]=2[C:11]([C:21]2[N:26]=[CH:25][N:24]=[C:23]([NH:24][C:23]3[CH:22]=[C:21]([NH:26][C:41](=[O:42])[C:40]4[CH:44]=[CH:45][CH:46]=[C:38]([N:37]([CH3:47])[CH3:36])[CH:39]=4)[CH:11]=[CH:2][CH:3]=3)[CH:22]=2)=[CH:10][CH:9]=1
Reactant: CN(C)c1cccc(C(=O)Cl)c1
Reactant: O=C(O)C(F)(F)F
Reactant: Nc1cccc(Nc2nccc(-c3cccc4c3oc3ccccc34)n2)c1
Agent: Cl
Solvent: c1ccncc1
Product: CN(C)c1cccc(C(=O)Nc2cccc(Nc3cc(-c4cccc5c4oc4ccccc45)ncn3)c2)c1

Procedure:
To a solution of N-(6-dibenzofuran-4-yl-pyrimidin-4-yl)-benzene-1,3-diamine trifluoroacetate (compound A2) (500 mg, 1.1 mmol) in pyridine (10 mL) is added at 10° C. 3-dimethylaminobenzoyl chloride HCl (288 mg, 1.21 mmol) portion wise. After 48 h at ambient temperature the mixture is evaporated and the crude product is purified by flash chromatography.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].N[C:13]1(O)[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH2:14]1.[CH2:23](O)C>CN(C1C=CN=CC=1)C>[N+:19]([C:16]1[CH:17]=[CH:18][C:13]([C:23]2[O:11][C:3]3[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=3[N:1]=2)=[CH:14][CH:15]=1)([O-:21])=[O:20]
Reactant: Nc1cc([N+](=O)[O-])ccc1O
Reactant: CCO
Reactant: NC1(O)C=CC([N+](=O)[O-])=CC1
Agent: CN(C)c1ccncc1
Product: O=[N+]([O-])c1ccc(-c2nc3cc([N+](=O)[O-])ccc3o2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 10 grams (0.05 mole) of 4-nitrophenylchloroxime are added 150 milliliters of ethanol and a catalytic amount of 4-(N,N-dimethyl)aminopyridine. 4.0 grams of 2-amino-4—nitrophenol are added to the mixture. The mixture is stirred under nitrogen at room temperature for ninety minutes, at which time another 3.7 grams of 1-amino-4-nitrophenol are added. The mixture is then stirred overnight at room temperature under a nitrogen blanket, cooled to 20° C. and filtered to yield 2-(p-nitrophenyl)-5-nitrobenzoxazole.
Reaction SMILES: [Br:1][C:2]1[C:13]([O:14][CH3:15])=[N:12][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH:10]([CH3:11])[C:4]=2[C:3]=1[Br:16].CI.[C:19]([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[Br:1][C:2]1[C:13]([O:14][CH3:15])=[N:12][C:5]2[CH2:6][CH2:7][N:8]([CH3:19])[CH2:9][CH:10]([CH3:11])[C:4]=2[C:3]=1[Br:16]
Reactant: COc1nc2c(c(Br)c1Br)C(C)CNCC2
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1nc2c(c(Br)c1Br)C(C)CN(C)CC2
Temperature: 25 °C
Reaction time: 72 h
Yield: 561.1 %

Procedure:
A mixture of 3,4-dibromo-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (32.5 mg, 9.30 μmol), MeI (5.8 μl, 93.0 μmol), Na2CO3 (19.7 mg, 18.3 μmol) and DMF (5 ml) was stirred for 3 d at room temperature. The reaction was quenched with sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 19.0 mg (56%) of 3,4-dibromo-2-methoxy-5,7-dimethyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 3.89 (s, 3H), 3.63 (m, 1H), 3.25 (m, 1H), 2.88 (m, 3H), 2.30 (s, 3H), 2.28 (dd, 1H), 2.14 (m, 1H), 1.26 (d, 3H) ppm.
Reaction SMILES: [Na].[C:2]([O:10][CH2:11][CH3:12])(=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[Cl:13][C:14]1[CH:15]=[C:16]2[C:25](=[CH:26][CH:27]=1)[C:24](Cl)=[C:23]1[C:18]([CH:19]=[CH:20][C:21]([O:29][CH3:30])=[CH:22]1)=[N:17]2.C1(C)C=CC=CC=1>C(O)C.C(=O)([O-])[O-].[K+].[K+]>[Cl:13][C:14]1[CH:15]=[C:16]2[C:25](=[CH:26][CH:27]=1)[C:24]([CH:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:2]([O:10][CH2:11][CH3:12])=[O:9])=[C:23]1[C:18]([CH:19]=[CH:20][C:21]([O:29][CH3:30])=[CH:22]1)=[N:17]2
Reactant: COc1ccc2nc3cc(Cl)ccc3c(Cl)c2c1
Reactant: CCOC(=O)CC(=O)OCC
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCOC(=O)C(C(=O)OCC)c1c2ccc(Cl)cc2nc2ccc(OC)cc12

Procedure:
To a solution of sodium (1.3 g, 52 mmol) in ethanol (50 mL) was added diethyl malonate (8.8 g 55 mmol) followed by 6,9-dichloro-2-methoxyacridine (9.68 g, 35 mmol) and toluene (5 mL). The mixture was heated to reflux for 24 h, diluted with aqueous potassium carbonate, extracted with ethyl acetate, dried, and concentrated in vacuo to give solid which was purified by flash column chromatography (silica gel, 5-12% methanol:dichloromethane) to give the title compound. MS(ES) m/e 402.2 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:11](=[O:13])[CH2:10][CH2:9][CH2:8]2.[CH3:14][CH:15](O)[CH:16]=[CH2:17].COC(OC)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:14]([CH:10]1[CH2:9][CH2:8][C:7]2[C:12](=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][CH:6]=2)[C:11]1=[O:13])[CH:15]=[CH:16][CH3:17]
Reactant: C=CC(C)O
Reactant: COc1cccc2c1C(=O)CCC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: COC(C)(C)OC
Product: CC=CCC1CCc2cccc(OC)c2C1=O
Yield: 22 %

Procedure:
13.7 g of 8-methoxy-1-tetralone were dissolved in 140 ml of toluene under argon and added to 13.3 ml of 3-buten-2-ol, 14.2 ml of 2,2-dimethoxypropane and 300 mg of p-toluenesulfonic acid. The reaction solution was heated to reflux for 90 hours. The solvent was removed in a vacuum and the residue was chromatographed on 500 g of silica gel firstly with hexane/ethyl acetate 9:1, then with hexane/ethyl acetate 4:1 and finally with hexane/ethyl acetate 1:1. In addition to large amounts of unreacted educt (8.3 g) there were obtained 3.95 g (22%) of 2-(2-buten-1-yl)-8-methoxy-1-tetralone as a yellow oil.
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[Cl:13][C:14]1[CH:22]=[C:21]([O:23][C:24]2[CH:25]=[N:26][C:27]([CH:31]3[CH2:33][CH2:32]3)=[C:28]([Cl:30])[CH:29]=2)[C:20]([Cl:34])=[CH:19][C:15]=1[C:16](O)=[O:17].[CH3:35][S:36]([NH2:39])(=[O:38])=[O:37]>CN(C)C1C=CN=CC=1.ClCCl>[Cl:13][C:14]1[CH:22]=[C:21]([O:23][C:24]2[CH:25]=[N:26][C:27]([CH:31]3[CH2:33][CH2:32]3)=[C:28]([Cl:30])[CH:29]=2)[C:20]([Cl:34])=[CH:19][C:15]=1[C:16]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[O:17]
Reactant: CS(N)(=O)=O
Reactant: O=C(O)c1cc(Cl)c(Oc2cnc(C3CC3)c(Cl)c2)cc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CS(=O)(=O)NC(=O)c1cc(Cl)c(Oc2cnc(C3CC3)c(Cl)c2)cc1Cl
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 12.4 %

Procedure:
4-Dimethylaminopyridine (51 mg, 0.42 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (80 mg, 0.42 mmol) were added to a suspension of 2,5-dichloro-4-(5-chloro-6-cyclopropylpyridin-3-yloxy)benzoic acid (Preparation 220, 100 mg, 0.28 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at room temperature for 20 minutes. Methylsulfonamide (40 mg, 0.42 mmol) was added and the reaction mixture was stirred at room temperature for 18 hours before concentrating in vacuo. The crude compound was purified by reverse phase column chromatography eluting with acetonitrile:water (from 5:95 to 95:5) followed by preparative HPLC to afford the title compound (15.1 mg, 12%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](I)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C([Li])CCC.[Si:19]([C:26]1[O:27][C:28]2[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:29]=2[C:30]=1[CH:31]=[O:32])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCCC1.C1(C)C=CC=CC=1>[Si:19]([C:26]1[O:27][C:28]2[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:29]=2[C:30]=1[C:31](=[O:32])[C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21]
Reactant: COc1ccc2c(C=O)c([Si](C)(C)C(C)(C)C)oc2c1
Reactant: COc1cc(I)cc(OC)c1OC
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: COc1ccc2c(C(=O)c3cc(OC)c(OC)c(OC)c3)c([Si](C)(C)C(C)(C)C)oc2c1
Temperature: 0 °C
Reaction time: 0.67 h

Procedure:
To a stirred solution of 3,4,5-trimethoxyiodobenzene (377 mg, 1.27 mmol) in dry tetrahydrofuran (1 mL) at −78° C. under nitrogen was added n-butyllithium (795 μL, 1.59 mmol, 2M solution in cyclohexane) and the reaction mixture was stirred at this temperature for 40 minutes. After this time a solution of 2-t-butyldimethylsilyl-3-formyl-6-methoxybenzofuran (310 mg, 1.07 mmol) in dry tetrahydrofuran (1 mL) was added to the reaction dropwise via syringe pipette. The reaction mixture was stirred at −60° C. for 20 minutes and then allowed to warm to 0° C., stirred for 10 minutes, quenched with saturated ammonium chloride solution (2 mL) and diluted with ethyl acetate (20 mL). The organic layer was washed with water (10 mL), dried over magnesium sulfate and the solvent was removed under vacuum to give a residue that was co-distilled with toluene. The crude product (908 mg) was dissolved in dry tetrahydrofuran (10 mL) and treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (900 mg, 1.59 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours (monitored by tlc) and then loaded onto silica (10 g) and purified by flash chromatography (silica gel, eluent=hexane/diethyl ether/triethylamine, 90:9:1) to afford the title compound as a light yellow paste that crystallised on standing (232 mg, 48%); 1H NMR (300 MHz, CDCl3) δ 7.14 (s, 2H, benzoyl Hs), 7.05 (d, 1H, J=2.45 Hz), 6.77 (dd, 1H, J=8.76, 2.17 Hz), 6.56 (d, 1H, J=8.38 Hz), 3.94 (s, 3H, OMe), 3.85 (s, 6H, 2×OMe), 3.78 (s, 3H, OMe), 1.00 (s, 9H), 0.28 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 190.51 (CO), 164.77, 158.23, 158.12, 152.64, 142.35, 133.19, 131.37, 123.19, 121.04, 119.63, 112.26, 107.03, 104.96, 95.00, 60.47, 55.81, 55.60, 55.13, 26.43, 17.29, −6.09.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C@:15](O)([CH2:16][C@@H:17]([O:31][CH2:32][O:33][CH3:34])[CH2:18][C@@H:19]2[O:27][C:28](=[O:30])[CH3:29])[CH:14]=[CH:13]3)[CH2:10][CH2:9]1)[CH3:7].C(O)(=O)C>C(OCCCC)(=O)C>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C:15]([CH2:16][C@@H:17]([O:31][CH2:32][O:33][CH3:34])[CH2:18][C@@H:19]2[O:27][C:28](=[O:30])[CH3:29])=[CH:14][CH:13]=3)[CH2:10][CH2:9]1)[CH3:7]
Reactant: COCO[C@H]1C[C@H](OC(C)=O)[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](C(C)C5OCCO5)CC[C@H]4[C@@H]3C=C[C@@]2(O)C1
Solvent: CCCCOC(C)=O
Solvent: CC(=O)O
Product: COCO[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)C5OCCO5)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Temperature: 100 °C
Yield: 29.7 %

Procedure:
In 10 ml of butyl acetate was dissolved 350 mg of 20-(1,3-dioxolan-2-yl)-1α-acetoxy-3β-(methoxymethyl)oxypregn-6-en-5α-ol, followed by addition of 0.2 ml of acetic acid. The mixture was stirred in an atmosphere of argon gas under heating at 100° C. for 12 hours. The reaction mixture was then worked up in the same manner as Example 124 to give 100 mg of 20-(1,3-dioxolan-2-yl)-1α--acetoxy-3β-(methoxymethyl)oxypregna-5,7-diene showing the following physical properties.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:16][CH:15]3[C:10]([C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)([N:11]=[C:12]([NH:17]C(=O)C4C=CC=CC=4)[S:13][CH2:14]3)[CH2:9]2)=[N:6][CH:7]=1.N1C=CC=CC=1.Cl.CON>C(O)C>[F:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:16][CH:15]3[C:10]([C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)([N:11]=[C:12]([NH2:17])[S:13][CH2:14]3)[CH2:9]2)=[N:4][CH:3]=1
Reactant: O=C(NC1=NC2(c3cccnc3)CN(c3ncc(F)cn3)CC2CS1)c1ccccc1
Agent: CON
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: NC1=NC2(c3cccnc3)CN(c3ncc(F)cn3)CC2CS1
Temperature: 70 °C
Reaction time: 17 h
Yield: 89.4 %

Procedure:
To a stirred solution of N-[6-(5-fluoropyrimidin-2-yl)-7a-(3-pyridyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (110 mg, 0.210 mmol) in ethanol (10 mL) are added pyridine (187 μL 2.31 mmol) and O-methylhydroxylamine hydrochloride (143 mg, 1.68 mmol). The mixture is heated at 70° C. with stirring for 17 hours. The solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using a 0-10% gradient of 0.14 M ammonia/methanol solution in dichloromethane to give the title compound (62 mg, 89%). ES/MS (m/e): 331 (M+1).
Reaction SMILES: [CH3:1][I:2].[C:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][S:10][C:11]1[C:15]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[N:14][S:13][N:12]=1)#[N:4]>CC(C)=O>[I-:2].[C:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][S:10][C:11]1[C:15]([C:16]2[CH:17]=[N+:18]([CH3:1])[CH:19]=[CH:20][CH:21]=2)=[N:14][S:13][N:12]=1)#[N:4]
Reactant: CI
Reactant: N#CCCCCCSc1nsnc1-c1cccnc1
Solvent: CC(C)=O
Product: C[n+]1cccc(-c2nsnc2SCCCCCC#N)c1
Product: [I-]
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Methyl iodide (1 ml, 15 mmol) was added to a solution of 3-(3-(5-cyanopentylthio)-1,2,5-thiadiazol-4-yl)pyridine (3 mmol) in acetone and the reaction mixture was stirred at room temperature for 20 h.and evaporated.
Reaction SMILES: [I:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH:19]([CH3:21])[CH3:20]>CN(C)C=O.O>[I:1][C:2]1[N:3]([CH:19]([CH3:21])[CH3:20])[N:4]=[CH:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CC(C)I
Reactant: CCOC(=O)c1c[nH]nc1I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cnn(C(C)C)c1I
Temperature: 60 °C
Reaction time: 2 h
Yield: 18.6 %

Procedure:
To a solution of ethyl 3-iodopyrazole-4-carboxylate (1.58 g, 5.94 mmol, Truong; et al. Bioorg. Med. Chem. Lett., 19, 4920 (2009)) in 20 mL N,N-dimethylformamide was added cesium carbonate (3.87 g, 11.9 mmol) and 2-iodopropane (0.89 mL, 8.90 mmol). The mixture was stirred 2 hours at 60° C. and then cooled to ambient temperature. The reaction mixture was diluted with 150 mL water and extracted with 2×100 mL diethyl ether. The combined organics were washed with 50 mL brine, dried over sodium sulfate, filtered and concentrated. The resultant oil was purified by flash chromatography (7-60% ethyl acetate/heptane gradient, 50 g silica) to yield 340 mg of ethyl 5-iodo-1-isopropyl-1H-pyrazole-4-carboxylate as a clear oil which crystallized on standing and 740 mg of ethyl 3-iodo-1-isopropyl-1H-pyrazole-4-carboxylate as a clear oil. Ethyl 5-iodo-1-isopropyl-1H-pyrazole-4-carboxylate: +APCI (M+H) 309.0; 1H NMR (400 MHz, CDCl3, δ): 8.05 (s, 1H) 4.82 (spt, J=6.6 Hz, 1H) 4.33 (q, J=7.2 Hz, 2H) 1.50 (d, J=6.6 Hz, 6H) 1.37 (t, J=7.1 Hz, 3H). Ethyl 3-iodo-1-isopropyl-1H-pyrazole-4-carboxylate: +APCI (M+H) 309.0; 1H NMR (400 MHz, CDCl3, δ): 7.84 (s, 1H) 4.52 (spt, J=6.7 Hz, 1H) 4.32 (q, J=7.1 Hz, 2H) 1.52 (d, J=6.6 Hz, 6H) 1.37 (t, J=7.1 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([CH:20]([S:28][CH2:29][CH2:30][C:31]([O:33]C)=[O:32])[S:21][CH2:22][CH2:23][C:24]([O:26]C)=[O:25])[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1.[OH-].[Li+].O>COCCOC>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([CH:20]([S:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])[S:21][CH2:22][CH2:23][C:24]([OH:26])=[O:25])[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: COC(=O)CCSC(SCCC(=O)OC)c1cccc(C=Cc2ccc3ccc(Cl)cc3n2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: COCCOC
Product: O=C(O)CCSC(SCCC(=O)O)c1cccc(C=Cc2ccc3ccc(Cl)cc3n2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of dimethyl ester (Step 2) (1.7 g) in 1,2-dimethoxyethane (60 ml ) was added lithium hydroxide (10 ml of 2N). The reaction mixture was stirred overnight at room temperature. H2O (100 ml) was added and the 1,2-dimethoxyethane was removed under vacuo. The solution was extracted with ethylacetate (300 ml). The aqueous phase was acidified to pH 3, extracted with ethylacetate (200 ml), dried and evaporated. Flash chromatography of the residue using 5% EtOH in CH2Cl2 with 1% of acetic acid afforded the title compound.
Reaction SMILES: [CH3:1][N:2]([C:7]1[C:12]([N+:13]([O-])=O)=[CH:11][CH:10]=[CH:9][N:8]=1)[S:3]([CH3:6])(=[O:5])=[O:4].[H][H].C(OCC)(=O)C>[Pd].CO>[NH2:13][C:12]1[C:7]([N:2]([CH3:1])[S:3]([CH3:6])(=[O:5])=[O:4])=[N:8][CH:9]=[CH:10][CH:11]=1
Reactant: [H][H]
Reactant: CN(c1ncccc1[N+](=O)[O-])S(C)(=O)=O
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CN(c1ncccc1N)S(C)(=O)=O

Procedure:
N-(3-Amino-pyridin-2-yl)-N-methyl-methanesulfonamide was prepared from N-methyl-N-(3-nitro-pyridin-2-yl)-methanesulfonamide (6.20 g, 26.8 mmol)(prepared as described in J. Med. Chem., 2007, 50, 3431) via hydrogenation using a Paar apparatus with 10% Palladium on Carbon (50% Wet) (5:45:50, Palladium:carbon black:Water, 5.71 g, 2.68 mmol) and Hydrogen (50 psi) in 2:1 ethyl acetate:methanol (150 mL). The mixture was shaken on a Paar apparatus until adsorption of hydrogen ceased. The mixture was degassed, backflushed with nitrogen, filtered through a plug of diatomaceous earth and rinsed with dichloromethane. The filtrate was evaporated under reduced pressure. Product isolated as brown solid (5.15 g, 95%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.85 (dd, J=3.7, 2.5 Hz, 1H), 7.10-7.08 (m, 2H), 4.24 (br s, 2H), 3.23 (s, 3H), 3.08 (s, 3H). MS=202 (MH)+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][C:5]2([CH3:13])[CH3:12].Cl[C:15]1[N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:18]=[N:17][N:16]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:12][C:5]1([CH3:13])[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([O:1][C:15]3[N:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[N:18]=[N:17][N:16]=3)[CH:3]=2)[C:7](=[O:11])[NH:6]1
Reactant: CC1(C)NC(=O)c2ccc(O)cc21
Reactant: Clc1nnnn1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)NC(=O)c2ccc(Oc3nnnn3-c3ccccc3)cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 97 %

Procedure:
A solution of lactam 62 (1.77 g, 10.0 mmol) and 5-chloro-1phenyl-1H-tetrazole (2.17 g, 12.0 mmol) in dry DMF (50 mL) is treated with solid K2CO3 (2.07 g, 15.0 mmol). The mixture is stirred overnight at rt, then poured into water and extracted with EtOAc (2×). The organic phase is washed with water (3×) and brine (2×), then dried (MgSO4), filtered, and evaporated. The residue is crystallized from CH2Cl2 to give a white solid, mp 202-204° C. The material weighs 3.10 g (97% yield) . 1H NMR (CDCl3) 7.90 (d, 1, J=8.3), 7.80 (m, 2), 7.60-7.55 (m, 4), 7.50-7.45 (m, 1), 6.78 (s, 1), 1.59 (s, 6); 13C NMR (CDCl3) 168.45, 158.80, 156.15, 155.27, 132.83, 129.81, 128.77, 125.78, 122.33, 119.44, 112.11, 59.14, 53.39, 27.59; MS (MW=321.3, EI, eE=70 eV) m/z 321 (M+), 306, 293, 278, 261, 250, 236, 222, 208, 187, 176, 161 (base peak), 145, 133, 117, 103, 91, 77, 65, 42.
Reaction SMILES: O[CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:5]=2[NH:4][C:3]1=[O:20].C(N(S(F)(F)[F:27])CC)C.C(=O)=O.CC(C)=O>C(Cl)Cl>[F:27][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:5]=2[NH:4][C:3]1=[O:20]
Reactant: O=C1Nc2ccc(Cl)cc2C(c2ccccc2)=NC1O
Reactant: CCN(CC)S(F)(F)F
Agent: O=C=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: O=C1Nc2ccc(Cl)cc2C(c2ccccc2)=NC1F

Procedure:
A well stirred suspension of 10 g (0.03 mol) of 3-hydroxy-1,3-dihydro-7-chloro-5-phenyl-2H-1,4-benzodiazepin-2-one and 500 ml of methylene chloride was cooled to -70°. Diethylaminosulfur trifluoride (25 ml, 0.2 mol) was then added dropwise with exclusion of moisture and air. On completion of the addition the dry-ice acetone bath was removed, the contents of the flask were allowed to warm up in about 25 minutes to -10° and the reaction then immediately quenched by pouring into a beaker containing 400-500 ml of ice water. (If the reaction mixture is allowed to warm to 25°, none of the desired product is obtained.) Vigorous stirring of the ice water mixture continued for 7 to 10 minutes. The organic layer was separated, dried over MgSO4 and evaporated under reduced pressure to give a light orange powder. The product was dissolved in hot benzene, treated with decolorizing charcoal and filtered hot. On addition of heptane to the benzene solution, followed by cooling in ice, 3-fluoro-1,3-dihydro-7-chloro-5-phenyl-2H-1,4-benzodiazepin-2-one crystallized out as a white powder, 8.19 g (82%): mp 190°-192° (decom.); 19F nmr (DMSO-d6) δ -161.5 ppm (d, d, J=56, 4 Hz, 1H), 1H nmr (DMSO-d6) δ 7.2-7.8 (m, 8H), δ 5.72 (d, J=56 Hz, 1H), δ 11.0 ppm (N--H).
Reaction SMILES: C([C:6]1[C:7](=[O:17])[O:8][C:9]2[C:14](C=1)=CC=C(O)C=2)(OCC)=O.[CH2:18]([O:20][CH:21]=[CH2:22])[CH3:19].C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[K+]>C(Cl)Cl>[CH2:18]([O:20][CH:21]([O:17][CH:7]([O:8][CH2:9][CH3:14])[CH3:6])[CH3:22])[CH3:19]
Reactant: C=COCC
Reactant: CCOC(=O)c1cc2ccc(O)cc2oc1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Product: CCOC(C)OC(C)OCC
Reaction time: 0.25 h
Yield: 26 %

Procedure:
To a slurry of 5.0 g (21 mMol) of 3-carbethoxy-7-hydroxycoumarin [H. Pechmann and E. Graezer, Chem. Ber. 34:378(1901)] in 100 mL of CH2Cl2 containing 5 mL of ethylvinyl ether was added 30 mg of p-toluenesulfonic acid. After 15 minutes, the reaction was poured into 100 mL of 10l% potassium hydroxide (KOH) solution. The organic phase was separated, washed with H2O, dried and evaporated. The residue was taken up in toluene and precipitated with hexane to give 1.73 g (26% yield) of the 1-ethoxyethyl ether as a solid, m.p. 70°-71° C.
Reaction SMILES: [N:1]12[Si:6]34[N:7]5[Si:4]61[N:5]3[Si:2]25[N:3]64.[N:8](O)=[Si]>>[N:1]12[Si:6]34[N:7]5[Si:4]61[N:5]3[Si:2]25[N:3]64.[SiH4:2].[NH3:8]
Reactant: ON=[Si]
Agent: N12[Si]34N5[Si]16N3[Si]25N46
Product: N
Product: [SiH4]

Procedure:
Alternatively, the silicon-rich barrier layer 23 can be silicon nitride or silicon oxynitride with a high refractive index. The determining and guiding physical characteristic is again the refractive index wherein the critical and preferred range for silicon nitride is between about 1.9 to 2.1 and for silicon oxynitride is between about 1.5 to 2.1. The silicon nitride layer is formed by the silane process under the typical conditions of power of 380 watts, pressure of 4.8 Torr, space of 480 mils, temperature of 400° C., silane flow of 130 ccm, ammonia flow of 55 ccm and nitrogen flow of 2000 to 4000 ccm. The silicon oxynitride layer is formed by the silane process under the typical conditions of power of 340 watts, pressure of 5 Torr, space of 410 mils, temperature of 400° C., silane flow of 75 ccm, ammonia flow of 50 ccm, nitrogen flow of 3500 to 4500 ccm, and dinitrogen oxide (N2O) flow of 75 ccm.