Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:11][C:12]1[C:17]([Cl:18])=[CH:16][N:15]=[C:14](Cl)[N:13]=1)=[O:4].[CH2:20]([N:22]1[CH2:28][CH2:27][C:26]2[CH:29]=[C:30]([NH2:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)[CH3:21].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+]>C(O)(C)C>[CH3:1][NH:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:11][C:12]1[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:33][C:30]2[CH:31]=[CH:32][C:25]3[CH2:24][CH2:23][N:22]([CH2:20][CH3:21])[CH2:28][CH2:27][C:26]=3[CH:29]=2)[N:13]=1)=[O:4]
Reactant: CCN1CCc2ccc(N)cc2CC1
Reactant: CNC(=O)[C@@H]1CCCC[C@@H]1Nc1nc(Cl)ncc1Cl
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Product: CCN1CCc2ccc(Nc3ncc(Cl)c(N[C@H]4CCCC[C@H]4C(=O)NC)n3)cc2CC1
Reaction time: 8 h
Yield: 46.7 %

Procedure:
cis-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexanecarboxylic acid methylamide (45 mg, 0.15 mmol) and 3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (30 mg, 0.16 mmol) were combined with camphorsulfonic acid (60 mg, 0.25 mmol) in 3 mL isopropyl alcohol and subjected to microwave irradiation at 120° C. for 2 hours. Solid sodium bicarbonate (a pinch) was added and the mixture was stored in a freezer overnight. The mixture was subsequently concentrated and the organics were partitioned between dichloromethane and saturated sodium bicarbonate solution (100 mL each). The organic layer was separated and was dried (sodium sulfate) to afford a solid which was purified on amine functionalized silica (10% to 100% ethyl acetate:hexane gradient elution) to afford 32 mg (47%) of a white solid. Mp: 143° C.; MS: 458.59 (M+H); 1H NMR (chloroform-d): δ 7.90 (s, 1H), δ 7.35-7.24 (m, 2H), δ 7.04 (d, J=8 Hz, 1H), δ 6.82 (s, 1H), δ 6.51 (d, J=7 Hz, 1H), δ 5.64 (br s, 1H), δ 4.34 (m, 1H), δ 2.97-2.54 (m, 6H), δ 2.79 (d, J=4 Hz, 3H), δ 2.36-0.78 (m, 13H), δ 1.12 (t, J=7 Hz, 3H).
Reaction SMILES: [C:1]1([N:7]2[C:11]([NH:12][CH:13]=[C:14]([C:20]([O:22]CC)=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:10][CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OCC)(=O)C1C(=CC=CC=1)C(OCC)=O>CCCCCC>[OH:22][C:20]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][N:12]=[C:11]2[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=[CH:9][C:10]=12
Reactant: CCOC(=O)C(=CNc1ccnn1-c1ccccc1)C(=O)OCC
Agent: CCOC(=O)c1ccccc1C(=O)OCC
Solvent: CCCCCC
Product: CCOC(=O)c1cnc2c(cnn2-c2ccccc2)c1O

Procedure:
A mixture of 18.1 g. (0.055 mole) of diethyl {[(1-phenyl-5-pyrazolyl)amino]methylene}malonate and 150 ml of diethyl phthalate was heated at 240-250° for 1 hour. The mixture was chilled and diluted with hexane. Chilling and filtering gave crystals which were washed with hexane and with hexane-ethanol (1:1) to give 11 g. (70%) of off white crystals, m.p. 149-150° C. From a similar small scale run 1.75 g. was recrystallized from 110 ml. of ethanol to give 1.58 g. of off white crystals, m.p. 149-150° C.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([N:11]=[C:12]([C:14]([NH2:16])=O)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[C:19]1([CH3:25])C=CC=C[CH:20]=1.COC(OC)N(C)C.Cl.[CH:35]([NH:38][NH2:39])(C)C.C(O)(=O)C>>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([N:11]=[C:12]([C:14]4[N:39]([CH:19]([CH3:25])[CH3:20])[N:38]=[CH:35][N:16]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1
Reactant: Cc1ccccc1
Reactant: NC(=O)c1nc2n(n1)CCOc1cc(Cl)ccc1-2
Reactant: CC(C)NN
Agent: COC(OC)N(C)C
Agent: Cl
Solvent: CC(=O)O
Product: CC(C)n1ncnc1-c1nc2n(n1)CCOc1cc(Cl)ccc1-2
Temperature: 102 °C
Yield: 98 %

Procedure:
To 9-Chloro-5,6-dihydrobenzo[f][1,2,4]triazolo[1,5-d][1,4]oxazepine-2-carboxamide (0.0053 g, 0.020 mmol) in toluene (0.160 mL, 1.50 mmol) was added 1,1-dimethoxy-N,N-dimethylmethanamine (0.0150 mL, 0.113 mmol), and the mixture was heated in a sealed flask to 102° C. for 2 hours while stirring. Next, the reaction mixture was cooled and concentrated to dryness, and isopropylhydrazine hydrochloride (0.00376 g, 0.0340 mmol) and acetic acid (0.0938 g, 1.56 mmol) were added and the reaction was sealed and heated to 102° C. overnight while stirring. Then, the reaction was concentrated to dryness and taken up in DMF, and purification by reverse phase HPLC gave 239 in 98% yield. 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J=2.6 Hz, 1H), 8.02 (s, 1H), 7.35 (dd, J=8.8, 2.6 Hz, 1H), 7.06 (d, J=8.8 Hz, 1H), 5.84-5.66 (m, 1H), 4.84-4.70 (m, 2H), 4.62-4.47 (m, 2H), 1.61 (s, 6H). LRMS m/z Calcd. for C15H15ClN6O: 330.09959. Found: 331.1 [M+1]
Reaction SMILES: CC[O-].[Na+].[NH2:5][C:6]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][N:7]=1.[N:14](OCCC(C)C)=O.[CH:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]=1[OH:32]>C(O)C>[CH3:13][O:12][C:11]1[C:6]([N:5]=[N:14][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[CH:24][C:23]=2[OH:32])=[N:7][CH:8]=[CH:9][CH:10]=1
Reactant: Oc1ccc2ccccc2c1
Reactant: COc1cccnc1N
Reactant: CC(C)CCON=O
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: COc1cccnc1N=Nc1c(O)ccc2ccccc12
Temperature: 25 °C

Procedure:
Next, a reaction flask was loaded with sodium ethylate (2.2 g) and ethanol (33 ml) and they were mixed. To the mixture, 2-amino-3-methoxypyridine (3.3 g) was added, and then isopentyl nitrite (3.7 g) was dropwise added in ten minutes with stirring. This was heated and stirred at the reflux temperature for 3.5 hours. The heating was stopped, and the mixture was cooled to room temperature. To this, 2-naphthol (2.7 g) dissolved in ethanol (5 ml) was dropwise added in 30 minutes. After stirring at room temperature for one hour, this mixture was heated to the reflux temperature, followed by stirring for additional 3 hours. The reaction mixture was filtrated and the filtrated crystals were recrystallized with methanol-water and further recrystallized with dioxane to give intended crystals (0.68 g).
Reaction SMILES: [Br:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][CH3:12])[C:4](=[O:13])[O:3]1.[C:14]1([P:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[Br-:1].[CH3:12][O:11][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[CH:2]([P+:20]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[O:3][C:4]2=[O:13]
Reactant: COc1cccc2c1C(Br)OC2=O
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1cccc2c1C([P+](c1ccccc1)(c1ccccc1)c1ccccc1)OC2=O
Product: [Br-]
Yield: 53.4 %

Procedure:
3-bromo-4-methoxyisobenzofuran-1(3H)-one (122) (3.15 g, 12.96 mmol) and triphenylphosphine (3.40 g, 12.96 mmol) were dissolved THF (50 mL) and heated at reflux over the weekend. The reaction was cooled and filtered to afford the desired material as a white solid (3.50 g, 53.4%); 1H NMR (400.132 MHz, CDCl3) δ 3.42 (3H, s), 7.10 (1H, d), 7.22-7.28 (1H, m), 7.47-7.53 (1H, m), 7.59-7.65 (6H, m), 7.74-7.80 (3H, m), 7.91-8.00 (6H, m), 9.80 (1H, s).
Reaction SMILES: N1(CCC(O)=O)C=CN=C1.[CH3:11][N:12]([CH3:26])[CH2:13][CH2:14][CH2:15][NH:16][C:17](=O)[CH2:18][CH2:19][N:20]1[CH:24]=[CH:23][N:22]=[CH:21]1.B.[N:28]1[C:36]2[C:31]3[C:32](=[CH:37][CH:38]=[CH:39][C:30]=3[C:29]=1S)[CH:33]=[CH:34][CH:35]=2>O1CCCC1.C(O)C>[CH3:11][N:12]([CH3:26])[CH2:13][CH2:14][CH2:15][N:16]([CH2:17][CH2:18][CH2:19][N:20]1[CH:24]=[CH:23][N:22]=[CH:21]1)[C:29]1[C:30]2[CH:39]=[CH:38][CH:37]=[C:32]3[C:31]=2[C:36](=[CH:35][CH:34]=[CH:33]3)[N:28]=1
Reactant: SC1=Nc2cccc3cccc1c23
Reactant: CN(C)CCCNC(=O)CCn1ccnc1
Agent: B
Agent: O=C(O)CCn1ccnc1
Solvent: C1CCOC1
Solvent: CCO
Product: CN(C)CCCN(CCCn1ccnc1)C1=Nc2cccc3cccc1c23

Procedure:
3(1H-imidazol-1-yl)propanoic acid is converted to its acid chloride which upon reaction with 3-dimethylaminopropylamine leads to N-(3-dimethylaminopropyl)-3-(1H-imidazol-1-yl)propanamide. Reduction with borane in tetrahydrofuran solution then gives N-(3-dimethylaminopropyl-N-3-(1H-imidazol-1yl))propanamine. Treatment of the latter compound with molar equivalents of benz(cd)indol-2-thiol and mercuric acetate in refluxing ethanol under the conditions of Example 55 then leads to the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:3]([O:17][CH3:18])=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1.[Li]CCCC.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C([O:36][C:37](=O)[C:38]1[CH:43]=[CH:42][C:41]([CH3:44])=[C:40]([N:45]2[CH:49]=[C:48]([C:50]3[N:51]([CH3:55])[CH:52]=[N:53][CH:54]=3)[CH:47]=[N:46]2)[CH:39]=1)C>C1COCC1.CO>[C:8]([C:6]1[CH:5]=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:3]([O:17][CH3:18])=[C:2]([NH:1][C:37](=[O:36])[C:38]2[CH:43]=[CH:42][C:41]([CH3:44])=[C:40]([N:45]3[CH:49]=[C:48]([C:50]4[N:51]([CH3:55])[CH:52]=[N:53][CH:54]=4)[CH:47]=[N:46]3)[CH:39]=2)[CH:7]=1)([CH3:10])([CH3:11])[CH3:9]
Reactant: CCOC(=O)c1ccc(C)c(-n2cc(-c3cncn3C)cn2)c1
Reactant: COc1c(N)cc(C(C)(C)C)cc1NS(C)(=O)=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CO
Product: COc1c(NC(=O)c2ccc(C)c(-n3cc(-c4cncn4C)cn3)c2)cc(C(C)(C)C)cc1NS(C)(=O)=O
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 33.6 %

Procedure:
A solution of N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methane-sulfonamide (81 mg, 0.261 mmol) in THF (4 mL) was stirred in a bath cooled to −78° C., and n-BuLi (0.22 mL, 0.548 mmol) was added slowly. The cold bath was removed, and the reaction was allowed to stir for 30 min. LHMDS (0.261 mmol) was then added slowly. The suspension was transferred dropwise to a stirring solution of compound 4-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzoic acid ethyl ester (81 mg, 0.261 mmol) in THF at 0° C. After 30 min cole MeOH was added and the mixture was partitioned between saturated NH4Cl and EtOAc, then extracted with EtOAc (3×). The organic combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated, and chromatographed (1% MeOH (with 5% NH4OH)/CH2Cl2 to 5% MeOH (with 5% NH4H)/CH2Cl2) to afford N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4-methyl-3-[4-(3-methyl-3H-imidazol-4-yl)-pyrazol-1-yl]-benzamide (47 mg, 33%) as an orange foam: ESI MS m/z=537 [C27H32N6O4S+H]+.
Reaction SMILES: [C:1]([C:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:11]=2)[NH:6][CH:5]=1)(=[O:3])[CH3:2].[C:20](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[C:1]([C:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:11]=2)[N:6]([CH3:20])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CCOC(=O)c1ccc2[nH]cc(C(C)=O)c(=O)c2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc2c(c1)c(=O)c(C(C)=O)cn2C
Temperature: 90 °C
Reaction time: 1 h
Yield: 60.2 %

Procedure:
To a suspension of ethyl 3-acetyl-4-oxo-1,4-dihydroquinoline-6-carboxylate (5.74 g, 22.14 mmol) in N,N-dimethylformamide (120 ml) was added potassium carbonate (9.18 g, 66.4 mmol) and methyl iodide (4.2 ml, 67.2 mmol). The mixture was stirred at 90° C. for 1 h. After cooling, the reaction was filtered, concentrated under high vacuum, diluted with dichloromethane/ethyl acetate, and filtered through a silica plug to afford ethyl 3-acetyl-1-methyl-4-oxo-1,4-dihydroquinoline-6-carboxylate (3.64 g, 13.32 mmol, 60.2% yield. LCMS: (M+H)+: 274.0.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:27][CH2:26][C:11]2([C:15](=[O:16])[N:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21](SC)=[CH:20][CH:19]=3)[CH2:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[O:29][S:30]([O-:32])=O.[K+].[OH-].[Na+].[CH2:36]1COCC1>O>[C:1]([O:5][C:6]([N:8]1[CH2:27][CH2:26][C:11]2([C:15](=[O:16])[N:14]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([S:30]([CH3:36])(=[O:32])=[O:29])=[CH:22][CH:23]=3)[CH2:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: C1CCOC1
Reactant: O=S([O-])OO
Reactant: CSc1ccc(CN2CCC3(CCN(C(=O)OC(C)(C)C)CC3)C2=O)cc1
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC2(CC1)CCN(Cc1ccc(S(C)(=O)=O)cc1)C2=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.1 %

Procedure:
To 7.73 g (19.8 mmol) of 2-(4-methylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester, previously dissolved in 100 mL of THF, were added 18.2 g (29.7 mmol) of Oxone® in 100 mL of water. The reaction mixture was agitated overnight at room temperature. Then 100 mL of 1N aqueous solution of sodium hydroxide were added and the solution was extracted with DCM (2×200 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure to yield 6.62 g (79.1%) of 2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a white solid.
Reaction SMILES: [OH:1][C:2]1[C:19]([CH:20]([CH3:23])[CH:21]=[CH2:22])=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C:11](=[O:24])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1.[H][H]>C(O)C.[Pd]>[OH:1][C:2]1[C:19]([CH:20]([CH3:23])[CH2:21][CH3:22])=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C:11](=[O:24])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1
Reactant: C=CC(C)c1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCC(C)c1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Yield: 65.9 %

Procedure:
To a solution of the known 3-hydroxy-2-(1-methyl-2-propenyl)estra-1,3,5(10)-trien-17-one (ref. Patton, 1962; Chemical Abstracts Registry Number [98543-85-2], 30 mg, 0.093 mmol) dissolved in 10 mL of anhydrous ethanol was added 20 mg of 5% Pd/C. The reaction flask was shaken under 2.7 atm. of hydrogen for 3 h. The reaction mixture was then filtered and the catalyst was washed with ethanol. After solvent removal, the crude product was purified by chromatography (silica gel eluted with 12.5% ethyl acetate in hexanes) and then recrystallized from methylene chloride-hexanes to give 20 mg of pure product: m.p. 186-187° C.; 1H NMR(CDCl3) δ 0.85-0.90 (m, 3H, CH3), 0.91 (s, 3H, CH3), 1.20-1.24 (m, 3H, CH3), 2.81-2.89 (m, 2H, CH2), 6.51 (s, 1H, Ar—H), 7.06 (s, 1H, Ar—H); 13C NMR(CDCl3) δ 12.17, 13.75, 20.44, 21.46, 25.93, 28.91, 29.83, 31.49, 33.87, 35.81, 38.33, 44.05, 48.01, 50.24, 115.37, 123.99, 124.17, 130.86, 131.88, 134.78, 157.267, 221.79.
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2].[N:20]12[CH2:30][CH2:29][CH2:28][N:27]=[C:26]1[CH2:25]CCCC2.N1CCC(CN)C1>C(#N)C>[NH2:20][CH2:30][CH:29]1[CH2:25][CH2:26][N:27]([C:10]2[C:11]([F:13])=[C:12]3[C:7]([C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4][N:3]3[CH2:1][CH3:2])=[CH:8][C:9]=2[F:15])[CH2:28]1
Reactant: C1CCC2=NCCCN2CC1
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(F)c21
Agent: NCC1CCNC1
Solvent: CC#N
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCC(CN)C3)c(F)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.6 %

Procedure:
A mixture of 0.50 g (1.84 mmole) of 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 5 ml of acetonitrile, 0.28 g (1.84 mmole) of 1,8-diazabicyclo [5.4.0]undec-7-ene and 0.19 g (1.94 mmole) of 3-pyrrolidinemethanamine was refluxed for one hour; then stirred at room temperature overnight. The reaction was filtered and the precipitate washed with ethyl ether to give 0.56 g of 7-[3-(aminomethyl)-1-pyrrolidinyl]-1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, mp 219°-221° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:11]O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:20]N1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:20][CH2:11][CH2:10][C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]
Reactant: CC(C)(C)OC(=O)N[C@H](CCO)C(=O)OC(C)(C)C
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H](CCBr)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 34 %

Procedure:
A mixture of 1.39 g (5.05 mmol) tert-butyl N-(tert-butoxycarbonyl)-D-homoserinate (prepared according to J. Org. Chem. 1988, 53, 1900-1903), 899 mg N-bromo succinimide (5.05 mmol), and 1.68 g polymer bound triphenylphosphine (loading approx. 3 mmol/g, approx. 5.0 mmol) in dichloromethane (17 mL) was stirred overnight at room temperature. All solids were removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel (2.5→25% ethyl acetate in hexane) to give 580 mg of the title compound (34% yield).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([C:21]4[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=4)[O:24][CH2:25][C:26](O)=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C1CN([P+](ON2N=[N:56][C:51]3[CH:52]=[CH:53][CH:54]=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C1(CN)CC1>C(Cl)Cl.CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([C:21]4[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=4)[O:24][CH2:25][C:26]([NH:56][CH2:51][CH:52]4[CH2:54][CH2:53]4)=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: O=C(O)COc1cccc(-c2nc(Nc3ccc4[nH]ncc4c3)c3ccccc3n2)c1
Reactant: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Agent: NCC1CC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(COc1cccc(-c2nc(Nc3ccc4[nH]ncc4c3)c3ccccc3n2)c1)NCC1CC1
Reaction time: 0.5 h

Procedure:
A suspension of 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid (80 mg, 0.16 mmol), PyBOP® (46 mg, 0.088 mmol), DIEA (28 μL, 0.16 mmol) in dry CH2Cl2:DMF (2:0.1 mL) was stirred at RT for 15 minutes. To this solution of activated acid was added cyclopropylmethanamine (7.1 mg, 0.10 mmol). After 30 minutes, 1.0 equivalent of DIEA and 0.55 equivalents of PyBOP® were added. After stirring the solution for 15 minutes, 0.65 equivalents of cyclopropylmethanamine were added and the mixture was stirred for an additional 30 minutes. The solvent was removed in vacuo and the crude product was purified using prep HPLC (20-45—90 mins) to afford 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(cyclopropylmethyl)acetamide. (60 mg, 0.13 mmol, 81%)
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)=O.[CH3:21][C:22]([C:24]1[CH:29]=[CH:28][C:27](OC)=[CH:26][CH:25]=1)=[O:23].[CH2:32](O)C>[OH-].[Na+].[Pd]>[CH3:32][C:27]1[CH:28]=[CH:29][C:24]([C:22]([CH2:21][CH2:1][C:3]2[CH:8]=[CH:7][C:6]([N:9]3[CH2:14][CH2:13][N:12]([C:15]4[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=4)[CH2:11][CH2:10]3)=[CH:5][CH:4]=2)=[O:23])=[CH:25][CH:26]=1
Reactant: O=Cc1ccc(N2CCN(c3ccncc3)CC2)cc1
Reactant: CCO
Reactant: COc1ccc(C(C)=O)cc1
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Product: Cc1ccc(C(=O)CCc2ccc(N3CCN(c4ccncc4)CC3)cc2)cc1

Procedure:
A solution of 1-(4-formylphenyl)-4-(4-pyridyl)piperazine (1.0 g), 4-methoxyacetophenone (503 mg) and concentrated sodium hydroxide (3 drops) in ethanol (25 ml) was stirred at ambient temperature overnight to give a solid which was dissolved in ethanol (100 ml) and hydrogenated over 10% palladium on charcoal to give a solid which was recrystallised from a mixture of ethyl acetate/isohexane to give 1-(4-[4-methylbenzoylethyl]-phenyl)-4-(4-pyridyl)piperazine (400 mg), m.p. 114-115° C.
Reaction SMILES: [CH2:1]([N:8]([CH2:10][CH2:11][O:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17]([C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=3)=[CH:18][C:19]([CH3:24])([CH3:23])[O:20]2)=[CH:15][CH:14]=1)C)C1C=CC=CC=1.[CH2:35]([N:37]([CH2:63][CH3:64])[CH2:38][CH2:39][O:40][C:41]1[CH:50]=[C:49]2[C:44]([C:45]([C:53]3[CH:62]=[CH:61][C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[CH:54]=3)=[CH:46][C:47]([CH3:52])([CH3:51])[O:48]2)=[CH:43][CH:42]=1)[CH3:36]>>[CH3:23][C:19]1([CH3:24])[CH2:18][CH:17]([C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)[C:16]2[C:21](=[CH:22][C:13]([O:12][CH2:11][CH2:10][NH:8][CH3:1])=[CH:14][CH:15]=2)[O:20]1.[CH2:63]([N:37]([CH2:35][CH3:36])[CH2:38][CH2:39][O:40][C:41]1[CH:50]=[C:49]2[C:44]([CH:45]([C:53]3[CH:62]=[CH:61][C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[CH:54]=3)[CH2:46][C:47]([CH3:51])([CH3:52])[O:48]2)=[CH:43][CH:42]=1)[CH3:64]
Reactant: CCN(CC)CCOc1ccc2c(c1)OC(C)(C)C=C2c1ccc2ccccc2c1
Reactant: CN(CCOc1ccc2c(c1)OC(C)(C)C=C2c1ccc2ccccc2c1)Cc1ccccc1
Product: CCN(CC)CCOc1ccc2c(c1)OC(C)(C)CC2c1ccc2ccccc2c1
Product: CNCCOc1ccc2c(c1)OC(C)(C)CC2c1ccc2ccccc2c1

Procedure:
2,2-Dimethyl-7-(2-methylaminoethoxy)-4-(2-naphthyl)chroman and 7-(2-diethylaminoethoxy)-2,2-dimethyl-4-(2-naphthyl)chroman were prepared from 7-[2-(N-benzyl-N-methylamino)ethoxy]-2,2-dimethyl-4-(2-naphthyl)-2H-chromene and 7-(2-diethylaminoethoxy)-2,2-dimethyl-4-(2-naphthyl)-2H-chromene respectively in a similar manner as colourless oils.
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[CH:7]=[C:8]([CH:15]2[O:20][CH2:19][CH2:18][CH2:17][O:16]2)[C:9]2[O:13][CH:12]=[CH:11][C:10]=2[CH:14]=1)CCC.Br[C:30]1[N:34]([CH3:35])[CH:33]=[N:32][CH:31]=1>>[O:20]1[CH2:19][CH2:18][CH2:17][O:16][CH:15]1[C:8]1[C:9]2[O:13][CH:12]=[CH:11][C:10]=2[CH:14]=[C:6]([C:30]2[N:34]([CH3:35])[CH:33]=[N:32][CH:31]=2)[CH:7]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C2OCCCO2)c2occc2c1
Reactant: Cn1cncc1Br
Product: Cn1cncc1-c1cc(C2OCCCO2)c2occc2c1

Procedure:
From tributyl-(7-[1,3]Dioxan-2-yl-benzofuran-5-yl)-stannane (0.40 g) and 5-bromo-1-methyl-1H-imidazole (0.13 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:10])[C@H:4]([CH2:6][CH:7]([CH3:9])[CH3:8])[NH2:5].ClCCl.Cl[CH2:15]/[CH:16]=[CH:17]\[CH2:18]Cl>CCCCCC.C(OCC)(=O)C>[CH3:8][CH:7]([CH3:9])[CH2:6][C@H:4]([N:5]1[CH2:18][CH:17]=[CH:16][CH2:15]1)[C:3]([O:2][CH3:1])=[O:10]
Reactant: ClC/C=C\CCl
Reactant: COC(=O)[C@@H](N)CC(C)C
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: ClCCl
Product: COC(=O)[C@H](CC(C)C)N1CC=CC1
Yield: 84.5 %

Procedure:
From L-leucine methyl ester (520 mg, 3.56 mmol), dichloromethane (1 ml) and cis-1,4-dichloro-2-butene (135 mg, 1.08 mmol). Flash chromatography: silica gel, gradient hexane:ethyl acetate (3:1 to 1:1) afforded the product (180 mg, 84%) as yellow oil.
Reaction SMILES: [Co:1].O.[C:3]([OH:6])(=[O:5])[CH3:4]>>[C:3]([O-:6])(=[O:5])[CH3:4].[Co+3:1].[C:3]([O-:6])(=[O:5])[CH3:4].[C:3]([O-:6])(=[O:5])[CH3:4]
Reactant: CC(=O)O
Reactant: [Co]
Solvent: O
Product: CC(=O)[O-]
Product: [Co+3]

Procedure:
Cobalt Micelle: Weighed 10 grams of cobaltic oxide (Co2O3), and added to 500 ml of distilled water. Added 11.5 ml of glacial acetic acid to yield a cobalt (III) acetate in solution. Added 100 grams of chrysotile (Union Carbide, high purity, grade 7) and diluted to 3.5 liters with distilled water. Heated the suspension to 100° C. and added 180 ml of 1 N sodium hydroxide to precipitate a cobalt micelle oxide onto the asbestos surface. Continued to heat and stir for 30 minutes. Removed from heat and allowed to cool. Collected the product by vacuum filtration on a Whatman #1 filter. A blue product was obtained. The product was air dried for 16 hours. The filter cake was dried at 330° F. for 90 minutes. The dry cake was fiberized by use of a blender at high speed for 1 minute. The sample was completely dissolved for elemental analysis by treatment with 20% by weight sodium peroxide at 850° C. Elemental analysis of the product is shown in Table I. Table II shows that the treatment increased the HF insoluble matter to 32% compared to 8.6% for an untreated chrysotile sample.