Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2]/[CH:3]=[CH:4]/[B:5]1[O:9][C:8]([CH3:11])([CH3:10])[C:7]([CH3:13])([CH3:12])[O:6]1.C(=O)([O-])[O-].[K+].[K+].[CH2:20](CN)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:29](#[N:31])C>C(OCC)(=O)C>[CH2:20]([N:31]([CH3:29])[CH2:2]/[CH:3]=[CH:4]/[B:5]1[O:9][C:8]([CH3:11])([CH3:10])[C:7]([CH3:13])([CH3:12])[O:6]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CC1(C)OB(/C=C/CCl)OC1(C)C
Reactant: NCCc1ccccc1
Reactant: CC#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: CN(C/C=C/B1OC(C)(C)C(C)(C)O1)Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 4 mL vial were mixed (E)-2-(3-chloroprop-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.195 ml, 0.988 mmol) and potassium carbonate (273 mg, 1.975 mmol) in anhydrous acetonitrile (2 ml). Benzylmethylamine (0.166 ml, 1.284 mmol) was added to this mixture, and the reaction was stirred vigorously overnight at room temperature. The reaction was diluted with ethyl acetate and washed with water and brine. The organic layer was dried with sodium sulfate, decanted, and concentrated to provide the title compound.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[N:12]=[C:11]([NH2:13])[N:10]=[C:9]([NH2:14])[C:8]=2[N+:15]([O-])=O)=[CH:4][CH:3]=1>CO.[Pd]>[CH3:1][C:2]1[O:6][C:5]([C:7]2[N:12]=[C:11]([NH2:13])[N:10]=[C:9]([NH2:14])[C:8]=2[NH2:15])=[CH:4][CH:3]=1
Reactant: Cc1ccc(-c2nc(N)nc(N)c2[N+](=O)[O-])o1
Agent: [Pd]
Solvent: CO
Product: Cc1ccc(-c2nc(N)nc(N)c2N)o1
Temperature: 40 °C
Yield: 95.5 %

Procedure:
A suspension of 6-(5-methyl-2-furyl)-5-nitropyrimidine-2,4-diamine (6.6 g, 29.6 mmol) and 10% Pd/C (0.66 g) in MeOH (100 mL) was heated at 40° C. under an atmosphere of H2 for 3 h, cooled to room temperature, filtered through Celite, and concentrated in vacuo to give the title compound (5.8 g, 99%) as an off-white solid; IR νmax (DR)/cm−1 3333, 2237, 1634, 1458, 1237, 1025, 963 and 828; NMR δH (400 MHz, DMSO) 6.77 (1H, dd, J 0.5, 3.2 Hz), 6.21-6.17 (3H, m), 5.14 (2H, s), 4.21 (2H, s), and 2.35 (3H, s).
Reaction SMILES: [C:1]([C:3]1[CH:15]=[CH:14][C:6]2[O:7][CH2:8][C:9]([CH3:13])([CH3:12])[CH2:10][O:11][C:5]=2[CH:4]=1)#[CH:2].I[C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1>>[CH3:13][C:9]1([CH3:12])[CH2:8][O:7][C:6]2[CH:14]=[CH:15][C:3]([C:1]#[C:2][C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)=[CH:4][C:5]=2[O:11][CH2:10]1
Reactant: C#Cc1ccc2c(c1)OCC(C)(C)CO2
Reactant: Oc1ccc(I)cc1
Product: CC1(C)COc2ccc(C#Cc3ccc(O)cc3)cc2OC1

Procedure:
The title compound is prepared in analogy to example 1 from 7-ethynyl-3,3-dimethyl-3,4-dihydro-2H-benzo[b][1,4]dioxepine (6) (example 1d) and 4-iodo-phenol as a brown solid. MS (ESI) 293.1 (M−H)−.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][CH3:26])=[CH:22][CH:23]=3)[C:18]([CH2:27][C:28]([OH:30])=[O:29])=[C:17]2[CH3:31])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:32](OC(=O)CC1C2C(=CC=C(OC)C=2)NC=1C)[CH3:33].[H-].[Na+].C(OC1C=CC(CCl)=CC=1)C1C=CC=CC=1>>[CH2:32]([O:29][C:28](=[O:30])[CH2:27][C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=2)[N:16]([CH2:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][CH:11]=2)[C:17]=1[CH3:31])[CH3:33]
Reactant: CCOC(=O)Cc1c(C)[nH]c2ccc(OC)cc12
Reactant: COc1ccc2c(c1)c(CC(=O)O)c(C)n2Cc1ccc(OCc2ccccc2)cc1
Agent: ClCc1ccc(OCc2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Product: CCOC(=O)Cc1c(C)n(Cc2ccc(OCc3ccccc3)cc2)c2ccc(OC)cc12

Procedure:
1-[(4-Benzyloxyphenyl)methyl]-5-methoxy-2-methyl-1H-indole-3-acetic acid. Using the method described in Example 6, Part A, 2.0 g (8.12 mmol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester, 0.325 g (8.12 mmol) of 60% NaH/mineral oil, and 1.88 g (8.12 mmol) of 4-benzyloxy-1-chloromethylbenzene were reacted to give on workup 800 mg of crude 1-[(4-benzyloxyphenyl)methyl]-5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester. The crude ester in 50 mL of MeOH and 15 mL of 1N NaOH was heated at reflux temperature for 3 hours and left standing for 16 hours. After diluting with water, the mixture was made acidic with 1N HCl and extracted with EtOAc. The EtOAc solution was dried (Na2SO4) and concentrated. The residue was crystallized from MeOH to give 280 mg (32% yield) of 1-[(4-benzyloxyphenyl)-methyl]-5-methoxy-2-methyl-1H-indole-3-acetic acid, mp, 175-179° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([S:20]([NH:23][CH2:24][CH2:25]P(=O)(O)O)(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1.NC1C=[CH:44][C:34]([CH2:35][P:36](=[O:43])([O:40]CC)[O:37]CC)=[CH:33][CH:32]=1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([S:20]([NH:23][C:24]2[CH:25]=[CH:44][C:34]([CH2:35][P:36](=[O:37])([OH:43])[OH:40])=[CH:33][CH:32]=2)(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1
Reactant: CCOP(=O)(Cc1ccc(N)cc1)OCC
Reactant: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCP(=O)(O)O)c2)C1
Product: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)Nc3ccc(CP(=O)(O)O)cc3)c2)C1

Procedure:
Compound 3 was prepared in an analogous manner to that of Compound 1 using diethyl 4-aminobenzylphosphonate (Intermediate 3.2) as the amine. 1H-NMR (300 MHz, CD3OD, ppm): 7.89 (d, J=7.8 Hz, 1H), 7.61˜7.66 (m, 1H), 7.52˜7.54 (m, 2H), 7.21˜7.20 (m, 2H), 7.11 (s, 1H), 6.95 (d, J=8.1 Hz, 2H), 6.73 (s, 1H), 4.51˜4.59 (m, 3H), 3.33 (s, 1H), 3.03˜2.89 (m, 6H). MS (ES, m/z): 541 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]1[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:22]#[N:23])[CH:20]=3)[NH:15][N:14]=1)[CH:7]=[CH:6]2.[OH:24]O.[OH-].[Na+].Cl>O.C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]1[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:22]([NH2:23])=[O:24])[CH:20]=3)[NH:15][N:14]=1)[CH:7]=[CH:6]2
Reactant: COc1ccc2cc(-c3n[nH]c4ccc(C#N)cc34)ccc2c1
Reactant: OO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc2cc(-c3n[nH]c4ccc(C(N)=O)cc34)ccc2c1
Temperature: 45 °C
Yield: 20 %

Procedure:
A mixture of 3-(6-methoxy-2-naphthyl)-1H-indazole-5-carbonitrile (0.230 g, 0.77 mmol), 95% ethanol (6 mL), aqueous 30% hydrogen peroxide (3 mL), and 6.0 N aqueous sodium hydroxide (1 mL, mmol) was heated at 45° C. for 3 h. The reaction mixture was diluted with water (30 mL) and acidified to pH 6 with 3 N hydrochloric acid. The solid was filtered and dried in a vacuum oven to give product (0.050 g, 20% yield): 1H NMR (DMSO-d6) δ 13.45 (s, 1H), 8.72 (s, 1H), 8.50 (s, 1H), 8.18 (s, 1H), 8.15 (d, 1H), 8.02 (d, 1H), 7.95 (d, 1H), 7.61 (d, 1H), 7.37 (m, 2H), 7.22 (dd, 1H); ES-MS (m/z) 318 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:22]=[C:21]4[C:17]([C:18]5[CH2:27][CH2:26][NH:25][CH2:24][C:19]=5[N:20]4[CH3:23])=[CH:16][CH:15]=3)[C:10](=[O:28])[CH:9]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.C=O.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:22]=[C:21]4[C:17]([C:18]5[CH2:27][CH2:26][N:25]([CH3:33])[CH2:24][C:19]=5[N:20]4[CH3:23])=[CH:16][CH:15]=3)[C:10](=[O:28])[CH:9]=2)=[C:4]([O:29][CH3:30])[CH:3]=1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: COc1cc(Cl)ccc1-c1ccn(-c2ccc3c4c(n(C)c3c2)CNCC4)c(=O)c1
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: COc1cc(Cl)ccc1-c1ccn(-c2ccc3c4c(n(C)c3c2)CN(C)CC4)c(=O)c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 88.7 %

Procedure:
4-(4-Chloro-2-methoxyphenyl)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one (83 mg, 0.20 mmol) and 37% aqueous formaldehyde (24 μL, 0.30 mmol) were dissolved in 1:1 MeOH/CH2Cl2 (1.4 mL) and stirred at room temperature for 45 min. Sodium triacetoxyborohydride (84 mg, 0.40 mmol) was added, and the reaction was stirred at ambient temperature for 30 min. The reaction mixture was neutralized with saturated NaHCO3 solution and extracted with CH2Cl2 (3×25 mL). The combined organics were washed with brine (25 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. Purification by flash column chromatography (12 g ISCO (1:1 hexanes/EtOAc)/(80:18:2 CH2Cl2/MeOH/NH4OH), 95:5 to 10:90 over 20 column volumes, hold for 10 column volumes) provided the title compound (77 mg, 89%) as a yellow film: 1H NMR (500 MHz, CDCl3) δ 7.55 (d, J=8.0 Hz, 1H), 7.41 (d, J=7.0 Hz, 1H), 7.35-7.34 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.07-7.03 (m, 2H), 7.00-6.99 (m, 1H), 6.81-6.80 (m, 1H), 6.43-6.42 (m, 1H), 3.87 (s, 3H), 3.66-3.65 (m, 2H), 3.48 (s, 3H), 2.87-2.86 (m, 2H), 2.81-2.80 (m, 2H), 2.58 (s, 3H).
Reaction SMILES: [O:1]1[C:3]2([CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:10])[CH2:5][CH2:4]2)[CH2:2]1.[CH:19]1([CH2:22][NH2:23])[CH2:21][CH2:20]1.Cl([O-])(=O)(=O)=O.[Li+]>>[CH:19]1([CH2:22][NH:23][CH2:2][C:3]2([OH:1])[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:10])[CH2:5][CH2:4]2)[CH2:21][CH2:20]1
Reactant: O=C(OCc1ccccc1)N1CCC2(CC1)CO2
Reactant: NCC1CC1
Agent: [Li+]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Product: O=C(OCc1ccccc1)N1CCC(O)(CNCC2CC2)CC1

Procedure:
The object product (2.53 g, 99%) was obtained in the same manner as in Example 24(1) and using benzyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (1.98 g), 1-cyclopropylmethanamine (570 mg) and lithium perchlorate (960 mg).
Reaction SMILES: [S-:1][C:2]#[N:3].[NH4+].[C:5](Cl)(=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH2:14][CH:15]1[CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1.O>CC(C)=O>[C:5]([NH:3][C:2]([NH:14][CH:15]1[CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1)=[S:1])(=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: N#C[S-]
Reactant: NC1Cc2ccccc2C1
Reactant: O=C(Cl)c1ccccc1
Agent: [NH4+]
Solvent: O
Solvent: CC(C)=O
Product: O=C(NC(=S)NC1Cc2ccccc2C1)c1ccccc1
Reaction time: 0.17 h
Yield: 72.6 %

Procedure:
To a stirred solution of ammonium thiocyanate (0.837 g.) in acetone (5 ml.) was added benzoyl chloride (1.406 g.) in acetone (10 ml.). The mixture was refluxed for 5 minutes then 2-aminoindane (1.332 g.) in acetone (10 ml.) was added quickly. Refluxing was continued for 10 minutes and the mixture poured into water (75 ml.) to give an oil which solidified on standing. Recrystallisation from ethanol/water afforded the title compound as pale yellow needles (2.151 g.), m.p. 130°-5° C.
Reaction SMILES: [S:1]1[CH2:6][CH2:5][CH2:4][S:3][CH2:2]1.C([Li])CCC.[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16]Br>C1COCC1.CCCCCC.C(Cl)Cl>[F:12][C:13]1[CH:14]=[C:15]([CH2:16][CH:2]2[S:3][CH2:4][CH2:5][CH2:6][S:1]2)[CH:18]=[CH:19][CH:20]=1
Reactant: Fc1cccc(CBr)c1
Reactant: C1CSCSC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: ClCCl
Product: Fc1cccc(CC2SCCCS2)c1
Temperature: -23 °C
Reaction time: 0.5 h
Yield: 66.6 %

Procedure:
1,3-Dithiane (12 g, 0.1 mol) was dissolved in 150 mL of anhydrous THF under a nitrogen atmosphere. The resultant solution was cooled to -78° C. and n-butyllithium (44 mL of a 2.5M solution of in hexane, 0.11 mol) was added. The reaction mixture was warmed to -23° C. and then stirred at -23° C. for 0.5 h. The reaction mixture was recooled to -78° C. and 25 g (0.135 mol) of 3-fluorobenzyl bromide was added over a 15 minute period. The reaction mixture was stirred for 3 h at ambient temperature and then diluted with methylene chloride, washed with aqueous ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was distilled to afford 15.2 g (66.7% yield) of the title compound, b.p. 135°-140° C. (0.5 mm Hg); MS DCI-NH3M/Z: 229 (M+H)+ ; 1H NMR (CDCl3) δ1.77-1.95 (1H, m), 2.05-2.18 (1H, m), 2.8-2.9 (4H, m), 3.02 (2H, d, J=7.5 Hz), 4.23 (1H, t, J=7.5 Hz), 6.9-7.1 (3H, m), 7.23-7.33 (1H, m).
Reaction SMILES: Br[CH2:2][CH:3]1[CH2:16][C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[CH:13]=3)[N:8]=[CH:7][C:6]=2[O:5][CH2:4]1.C(OC([N:26]1[CH2:31][CH2:30][CH:29]([CH2:32][NH2:33])[CH2:28][CH2:27]1)=O)(C)(C)C.[O:34]=[C:35]1[NH:40][C:39]2[CH:41]=[C:42]([C:45](O)=[O:46])[CH:43]=[CH:44][C:38]=2[S:37][CH2:36]1>>[CH3:18][O:17][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]1[O:5][CH2:4][CH:3]([CH2:2][N:26]3[CH2:27][CH2:28][CH:29]([CH2:32][NH:33][C:45]([C:42]4[CH:43]=[CH:44][C:38]5[S:37][CH2:36][C:35](=[O:34])[NH:40][C:39]=5[CH:41]=4)=[O:46])[CH2:30][CH2:31]3)[CH2:16][C:15]2=1
Reactant: O=C1CSc2ccc(C(=O)O)cc2N1
Reactant: CC(C)(C)OC(=O)N1CCC(CN)CC1
Reactant: COc1ccc2ncc3c(c2c1)CC(CBr)CO3
Product: COc1ccc2ncc3c(c2c1)CC(CN1CCC(CNC(=O)c2ccc4c(c2)NC(=O)CS4)CC1)CO3

Procedure:
The titled compound is prepared as an off-white lyophilized powder following Scheme 1 and in analogy to Example 1 using 3-bromomethyl-6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthrene, 4-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester and 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid as starting material.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].Cl.[Cl:9][C:10]1[CH:11]=[CH:12][C:13]2[N:22]([C:23]([CH:25]3[CH2:30][CH2:29][CH:28]([CH2:31][NH:32][C:33](=[O:42])[CH2:34][CH2:35][CH:36]4[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]4)[CH2:27][CH2:26]3)=[O:24])[CH2:21][C:20]3[CH:19]=[N:18][N:17]([CH3:43])[C:16]=3[NH:15][C:14]=2[CH:44]=1>CN(C=O)C.C(N(CC)CC)C>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]2[N:22]([C:23]([CH:25]3[CH2:30][CH2:29][CH:28]([CH2:31][NH:32][C:33](=[O:42])[CH2:34][CH2:35][CH:36]4[CH2:37][CH2:38][N:39]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH2:40][CH2:41]4)[CH2:27][CH2:26]3)=[O:24])[CH2:21][C:20]3[CH:19]=[N:18][N:17]([CH3:43])[C:16]=3[NH:15][C:14]=2[CH:44]=1
Reactant: CCCCCCBr
Reactant: Cn1ncc2c1Nc1cc(Cl)ccc1N(C(=O)C1CCC(CNC(=O)CCC3CCNCC3)CC1)C2
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCCCCN1CCC(CCC(=O)NCC2CCC(C(=O)N3Cc4cnn(C)c4Nc4cc(Cl)ccc43)CC2)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A solution of 1-bromohexane (0.83 mg, 0.005 mmol) in DMF (0.05 ml) was added to a solution of N-[4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-cyclohexylmethyl]-3-piperidin-4-yl-propionamide hydrochloride (Compound number 237) (2.57 mg, 0.005 mmol) in DMF (0.05 ml) and triethylamine (0.0021 ml). The mixture was stirred for 20 h at room temperature then solvents were removed in vacuo to yield the title compound. (ESI)+: [M+H]+=597.6/599.6
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][S:10][C:11]2[NH:26][C:14]3=[N:15][C:16]([O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[C:17]([CH3:19])[CH:18]=[C:13]3[N:12]=2)[C:4]=1[CH3:27].ClC1C=CC=C(C(OO)=[O:36])C=1.C(=O)(O)[O-].[Na+]>CO.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][S:10]([C:11]2[NH:26][C:14]3=[N:15][C:16]([O:20][CH2:21][C:22]([F:23])([F:24])[F:25])=[C:17]([CH3:19])[CH:18]=[C:13]3[N:12]=2)=[O:36])[C:4]=1[CH3:27]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccnc(CSc2nc3cc(C)c(OCC(F)(F)F)nc3[nH]2)c1C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Product: COc1ccnc(CS(=O)c2nc3cc(C)c(OCC(F)(F)F)nc3[nH]2)c1C
Reaction time: 2 h
Yield: 92.6 %

Procedure:
2-(((4-Methoxy-3-methyl-2-pyridinyl)methyl)thio)-6-methyl-5-(2,2,2-trifluoroethoxy)-3H-imidazo[4,5-b]pyridine (270 mg, 0.68 mmol) was dissolved in a mixture of methanol (2 ml) and toluene (18 ml), and a solution of metachloroperbenzoic acid (162 mg) in a mixture of methanol (0.5 ml) of toluene (0.5 ml) were added dropwise at −40° C. under nitrogen flow. After stirred at −20° C. to −40° C. for 2 hours, a sodium bicarbonate solution was added, the mixture was extracted with chloroform (30 ml), and dried over sodium sulfate. The solvent was evaporated, and the solid was precipitated from a mixture of chloroform and n-hexane to yield the title compound (263 mg, 0.63 mmol, 93%) as a purple gray solid.
Reaction SMILES: [CH3:1][C:2]([CH3:4])=O.C(O[K])(C)(C)C.[N+:11]([C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17])([O-:13])=[O:12]>CS(C)=O.C(OCC)(=O)C>[CH3:1][C:2]1[NH:17][C:16]2[C:15]([CH:4]=1)=[C:14]([N+:11]([O-:13])=[O:12])[CH:20]=[CH:19][CH:18]=2
Reactant: CC(C)=O
Reactant: Nc1cccc([N+](=O)[O-])c1
Agent: CC(C)(C)O[K]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: Cc1cc2c([N+](=O)[O-])cccc2[nH]1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Acetone (1.0 mL) and tert-butoxy potassium (2.7 g) were added to a solution of 3-nitroaniline (1.38 g) in dimethylsulfoxide (20 ml), and the reaction solution was stirred at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate, and washed successively with an aqueous ammonium chloride solution and a saturated saline solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under vacuum. The residue was purified by column chromatography on silica gel (developing solvent:hexane-ethyl acetate) to obtain 2-methyl-4-nitro-1H-indole.
Reaction SMILES: [OH:1][C@H:2]1[CH2:22][C@@:21]2([CH3:23])[C@@H:13]([CH2:14][C@@H:15]([OH:25])[C@:16]2([OH:24])[C:17](=[O:20])[CH2:18][OH:19])[C@H:12]2[C@H:3]1[C@:4]1([CH3:27])[C:9]([CH2:10][CH2:11]2)=[CH:8][C:7](=[O:26])[CH2:6][CH2:5]1.[CH:28]([CH:30]=[N+]=[N-])=[CH2:29]>>[CH2:30]([O:25][C@@H:15]1[CH2:14][C@@H:13]2[C@:21]([CH3:23])([CH2:22][C@H:2]([OH:1])[C@H:3]3[C@H:12]2[CH2:11][CH2:10][C:9]2[C@:4]3([CH3:27])[CH2:5][CH2:6][C:7](=[O:26])[CH:8]=2)[C@@:16]1([OH:24])[C:17](=[O:20])[CH2:18][OH:19])[CH:28]=[CH2:29]
Reactant: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1C[C@@H](O)[C@]2(O)C(=O)CO
Reactant: C=CC=[N+]=[N-]
Product: C=CCO[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3[C@@H](O)C[C@]2(C)[C@@]1(O)C(=O)CO

Procedure:
11β,16α,17,21-Tetrahydroxypregn-4-ene-3,20-dione, 16,17-cycloborate is added to a solution of vinyl diazomethane in 1:1 methanol-ether at 0°C until nitrogen evolution ceases. The solvent is evaporated to yield the title compound.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH3:7][S:8]([CH3:10])=O.[F:11][C:12]([F:17])([F:16])[C:13]([OH:15])=[O:14].[OH:18][CH2:19]/[C:20](/[CH3:50])=[CH:21]/[C@@H:22]([N:26]([CH3:49])[C:27](=[O:48])[C@@H:28]([NH:33][C:34](=[O:47])[C@@H:35]([NH:45][CH3:46])[C:36]([CH3:44])([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH3:37])[C:29]([CH3:32])([CH3:31])[CH3:30])[CH:23]([CH3:25])[CH3:24].C(N(CC)CC)C>ClCCl>[F:11][C:12]([F:17])([F:16])[C:13]([OH:15])=[O:14].[CH3:7][S+:8]([CH3:10])[C:41]1[CH:42]=[CH:43][C:38]([C:36]([CH3:44])([CH3:37])[C@@H:35]([C:34]([NH:33][C@H:28]([C:27]([N:26]([C@@H:22]([CH:23]([CH3:24])[CH3:25])/[CH:21]=[C:20](\[CH3:50])/[CH:19]=[O:18])[CH3:49])=[O:48])[C:29]([CH3:30])([CH3:32])[CH3:31])=[O:47])[NH:45][CH3:46])=[CH:39][CH:40]=1.[CH3:46][NH:45][C@H:35]([C:34]([NH:33][C@H:28]([C:27]([N:26]([C@@H:22]([CH:23]([CH3:25])[CH3:24])/[CH:21]=[C:20](\[CH3:50])/[CH:19]=[O:18])[CH3:49])=[O:48])[C:29]([CH3:32])([CH3:31])[CH3:30])=[O:47])[C:36]([CH3:44])([CH3:37])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: CN[C@H](C(=O)N[C@H](C(=O)N(C)[C@H](/C=C(\C)CO)C(C)C)C(C)(C)C)C(C)(C)c1ccccc1
Reactant: CS(C)=O
Agent: O=C(Cl)C(=O)Cl
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN[C@H](C(=O)N[C@H](C(=O)N(C)[C@H](/C=C(\C)C=O)C(C)C)C(C)(C)C)C(C)(C)c1ccc([S+](C)C)cc1
Product: CN[C@H](C(=O)N[C@H](C(=O)N(C)[C@H](/C=C(\C)C=O)C(C)C)C(C)(C)C)C(C)(C)c1ccccc1
Temperature: 25 °C
Yield: 129.9 %

Procedure:
Following the procedure described in J. Org. Chem. 1994, 59(7), 1771, to a solution of oxalyl chloride (0.17 mmol) in dichloromethane at −78° C. is added a solution of dimethylsulfoxide (0.348 mmol, 0.025 mL) in dichloromethane dropwise. After 10 min a solution of (2S)-N-[(1S,2E)-4-hydroxy-1-isopropyl-3-methyl-2-butenyl]-N,3,3-trimethyl-2-{[(2S)-3-methyl-2-(methylamino)-3-phenylbutanoyl]amino}butanamide trifluoroacetic acid (83 mg, from Example 81) in dichloromethane is added dropwise. After 20 min triethylamine (0.725 mmol, 0.1 mL) is added dropwise. The reaction mixture is allowed to warm to 25° C. then washed with water and dried over anhydrous sodium sulfate. Concentration in vacuo and purification by reverse phase HPLC (0.01% aqueous trifluoroacetic acid/acetonitrile gradient system) gave the trifluoracetic acid salt of N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N1,3-dimethyl-L-valinamide as a white powder (43 mg) MS (ES): m/z 458.1 (M+H) and 4-(dimethylsulfonio)-N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N1,3-dimethyl-L-valinamide trifluoroacetate as a clear glass (28 mg) MS (ES): m/z 518.0 (M+).
Reaction SMILES: [Br:1][C:2]1[C:7]([OH:8])=[C:6]([Br:9])[C:5]([Br:10])=[C:4]([Br:11])[C:3]=1[Br:12].[C:13](=[O:16])([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:22][C:23]1([CH2:27]Cl)[CH2:26][O:25][CH2:24]1>O.CN(C)C=O>[Br:1][C:2]1[C:7]([O:8][CH2:22][C:23]2([CH2:27][O:16][C:13]3[C:6]([Br:9])=[C:5]([Br:10])[C:4]([Br:11])=[C:3]([Br:12])[C:2]=3[Br:1])[CH2:26][O:25][CH2:24]2)=[C:6]([Br:9])[C:5]([Br:10])=[C:4]([Br:11])[C:3]=1[Br:12]
Reactant: ClCC1(CCl)COC1
Reactant: O=C([O-])[O-]
Reactant: Oc1c(Br)c(Br)c(Br)c(Br)c1Br
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Brc1c(Br)c(Br)c(OCC2(COc3c(Br)c(Br)c(Br)c(Br)c3Br)COC2)c(Br)c1Br
Temperature: 143 °C

Procedure:
A mixture of pentabromophenol (100 g., 0.2 moles), potassium carbonate (30 g., 0.22 moles), potassium iodide (0.5 g.), dimethyl formamide (180 ml.) and 3,3-bischloromethyl oxetane (15.5 g., 0.1 moles) was stirred in a nitrogen atmosphere and heated to 143° C. for 5 hours. The partially cooled reaction mixture was poured into 1 liter of water. The resulting solid 3,3-bis[pentabromophenoxymethyl]oxetane was collected by filtration and washed on the funnel with water and with ethanol. The yield was 93 g. A small sample was recrystallized from a large volume of dioxane. The recrystallized material melted at 281°-284° C.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].[C:5]1(=[O:11])[O:10][C:8](=[O:9])[CH:7]=[CH:6]1.N(C(C)(C)C#N)=NC(C)(C)C#N.[OH-:24].[Na+]>C1(=O)CCCCC1.O.CC(C)=O>[CH2:1]=[CH:2][CH:3]=[CH2:4].[C:5]([OH:10])(=[O:11])/[CH:6]=[CH:7]\[C:8]([OH:24])=[O:9]
Reactant: O=C1C=CC(=O)O1
Reactant: [OH-]
Agent: C=CC=C
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Solvent: O=C1CCCCC1
Product: O=C(O)/C=C\C(=O)O
Reaction time: 4 h

Procedure:
A polymerization was carried out at 70° C. for 4 hours using 54.1 g. of butadiene, 98.1 g. of maleic anhydride and 1.7 g. of azobisisobutyronitrile in 750 cc. of acetone. There was obtained 106.0 g. of a pale yellow copolymer with an intrinsic viscosity of 0.50 as measured in cyclohexanone at 30° C. (All measurements are done hereinbelow under the same conditions.) A reaction was carried out at 80° C. for 1 hour using 15.2 g. of the copolymer, 6.0 g. of sodium hydroxide and 131 g. of water to form an aqueous solution of butadiene-maleic acid copolymer sodium salt. The aqueous solution, an aqueous calcium-chloride solution at a concentration of 0.1 M/l, 30% aqueous solution of sodium lauryl sulfate (LAS) and water were employed together with THPA in an amount equal to the copolymer salt to prepare compositions shown in Table 1. Whereas aqueous gel was formed with the compositions of Examples 1-5, no aqueous gel was formed or the polymer was precipitated with the compositions of Comparative Examples 1-3, in which one of the essential components was not contained.