Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([OH:16])[C:13]([CH3:22])([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23]I.[H-].[Na+]>CN(C)C=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([O:16][CH3:23])[C:13]([CH3:22])([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C1(C)CN(C(=O)OCc2ccccc2)CC1O
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1(C)CN(C(=O)OCc2ccccc2)CC1OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 65.7 %

Procedure:
To a solution of ethyl 1-benzyloxycarbonyl-4-hydroxy-3-methylpyrrolidine-3-carboxylate (0.55 g, 1.8 mmol) in N,N-dimethylformamide (10 mL), methyl iodide (0.22 mL, 3.6 mmol) and sodium hydride (55% in oil, 117 mg, 2.7 mmol) were added in an ice bath, and the mixture was stirred at room temperature for 1 hour. Ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL×3). The extract was washed with water (20 mL×3) and saturated aqueous solution of sodium chloride (20 mL) in this order, and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 2:1) to obtain 0.38 g (66%) of the title compound as a pale yellow oily product.
Reaction SMILES: [Br:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C@H:7]([C@H:9]([OH:18])[CH2:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH3:8])=[CH:4][CH:3]=1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].N1C=CN=C1>ClCCl>[Br:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C@@H:7]([CH3:8])[C@H:9]([O:18][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH2:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[CH:4][CH:3]=1
Reactant: C[C@H](Oc1ccc(Br)cc1)[C@H](O)CCc1cccnc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: C[C@H](Oc1ccc(Br)cc1)[C@@H](CCc1cccnc1)O[Si](C)(C)C(C)(C)C
Reaction time: 24 h
Yield: 93.6 %

Procedure:
To a solution of (2S,3R)-2-(4-bromophenoxy)-5-pyridin-3-ylpentan-3-ol (2.01 g, Example 15d)) in dry dichloromethane (50 ml) was added tert-butyldimethylsilyl chloride (1.81 g) and imidazole (0.814 g) and the resulting solution stirred for 24 hours, concentrated and the residue purified by column chromatography on silica gel eluting with dichloromethane:diethyl ether (1:1) to afford the sub-title compound as an oil (2.52 g).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([NH:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]2)=[O:11])=[CH:4][C:3]=1[Cl:27]>Cl>[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([NH:12][CH2:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:11])=[CH:4][C:3]=1[Cl:27]
Reactant: COc1nc(N)c(Cl)cc1C(=O)NCC1CCN(C(=O)OC(C)(C)C)CC1
Agent: Cl
Product: COc1nc(N)c(Cl)cc1C(=O)NCC1CCNCC1
Yield: 85.1 %

Procedure:
A solution of 1,1-dimethylethyl 4-[({[6-amino-5-chloro-2-(methyloxy)-3-pyridinyl]carbonyl}amino)methyl]-1-piperidinecarboxylate (step 1 in example 1, 6.20 g, 15.5 mmol) in 10% methanolic hydrochloric acid (130 ml) was stirred at room temperature for 7 h. The mixture was concentrated to ca. 30 ml. The residue was basified with 2 N aqueous sodium hydroxide (pH=10) and the aqueous layer was extracted with dichloromethane (80 ml×3). The combined organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on a column of aminopropyl silica gel eluting with methanol/dichloromethane (1:15) to give 3.94 g (85%) of the title compound as a white solid.
Reaction SMILES: CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20]([CH:35]=[CH:36][C:37]=1[F:38])[NH:21][C:22]1[C:31]2[C:30]([OH:32])=[CH:29][C:28]([O:33][CH3:34])=[CH:27][C:26]=2[N:25]=[CH:24][N:23]=1.[Si:39]([O:46][C@@H:47]1[CH2:51][N:50]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:49]([CH2:59]O)[CH2:48]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Si:39]([O:46][C@@H:47]1[CH2:51][N:50]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:49]([CH2:59][O:32][C:30]2[CH:29]=[C:28]([O:33][CH3:34])[CH:27]=[C:26]3[C:31]=2[C:22]([NH:21][C:20]2[CH:35]=[CH:36][C:37]([F:38])=[C:18]([Cl:17])[CH:19]=2)=[N:23][CH:24]=[N:25]3)[CH2:48]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40]
Reactant: CC(C)(C)OC(=O)N1C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H]1CO
Reactant: COc1cc(O)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1
Agent: CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc(OC[C@@H]2C[C@H](O[Si](C)(C)C(C)(C)C)CN2C(=O)OC(C)(C)C)c2c(Nc3ccc(F)c(Cl)c3)ncnc2c1
Temperature: 25 °C
Reaction time: 28 h
Yield: 44.6 %

Procedure:
Di-tert-butylazodicarboxylate (DTAD, 1.38 g) was added in one portion to a mixture of 4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol (1.28 g), tert-butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)-pyrrolidine-1-carboxylate (1.66 g), and triphenylphosphine (1.58 g) in DCM (100 ml) at room temperature, under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 28 hours and then concentrated in vacuo to leave a brown oil. Purification by column chromatography, using 0-50% ethyl acetate in hexane as eluent, gave tert-butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]-oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]-pyrrolidine-1-carboxylate as a white solid (1.13 g, 45%); Mass spectrum MH+ 633.
Reaction SMILES: [CH:1](=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5].[OH-].[K+].[C:9]1(=[O:14])[CH2:13][CH2:12][CH2:11][CH2:10]1>[OH-].[Na+].C(=C1CCCC1=O)CCCC.O>[OH:6][CH:1]([CH:10]1[CH2:11][CH2:12][CH2:13][C:9]1=[O:14])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: O=C1CCCC1
Reactant: CCCCC=O
Agent: CCCCC=C1CCCC1=O
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: CCCCC(O)C1CCCC1=O
Temperature: 15 °C
Yield: 40 %

Procedure:
Valeraldehyde having an acid value of 7.3 mg-KOH/g was used as the starting material. 178 g (2.14 mol) cyclopentanone, 80 g water and 0.62 g (0.007 mol) 48% NaOH were introduced into a 500-mL four-necked flask, then the mixture was cooled to 15° C. under stirring, and 80.4 g (0.93 mol) valeraldehyde was added dropwise at the same temperature over 5 hours. Thereafter, the mixture was stirred at the same temperature for 3 hours. After the reaction was finished, the mixture was neutralized and analyzed in the same manner as in Example 1. The result indicated that the reaction mixture contained 62.9 g (0.37 mol) 2-(1-hydroxy-n-pentyl)cyclopentanone (yield 40.0%) and 0.55 g (0.004 mol) 2-pentylidene cyclopentanone.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[F:17][C:18]1[CH:24]=[C:23]([CH3:25])[C:22]([OH:26])=[CH:21][C:19]=1[NH2:20]>C(O)(C)C>[ClH:2].[F:17][C:18]1[CH:24]=[C:23]([CH3:25])[C:22]([OH:26])=[CH:21][C:19]=1[NH:20][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Reactant: Cc1cc(F)c(N)cc1O
Agent: Cl
Solvent: CC(C)O
Product: COc1cc2ncnc(Nc3cc(O)c(C)cc3F)c2cc1OC
Yield: 62.7 %

Procedure:
A mixture of 4-chloro-6,7-dimethoxyquinazoline hydrochloride (2.5 g, 9.6 mmol), (prepared as described for the starting material in Example 1 but without the aqueous work up), and 2-fluoro-5-hydroxy-4-methylaniline (1.48 g, 10.5 mmol) in isopropanol (150 ml) was heated at reflux for 2 hours. The mixture was allowed to cool, the solid product collected by filtration, washed with isopropanol and dried to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6,7-dimethoxyquinazoline hydrochloride (2.2 g, 71 %).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][NH:5][C:6](=O)[C:7]([F:10])([F:9])[F:8].B.C1COCC1>O1CCCC1>[Cl:1][CH2:2][CH2:3][CH2:4][NH:5][CH2:6][C:7]([F:10])([F:9])[F:8]
Reactant: O=C(NCCCCl)C(F)(F)F
Agent: B
Solvent: C1CCOC1
Product: FC(F)(F)CNCCCCl
Temperature: 80 °C
Reaction time: 3 h

Procedure:
Into a 250-mL round-bottom flask, was placed N-(3-chloropropyl)-2,2,2-trifluoroacetamide (6 g, 31.65 mmol, 1.00 equiv), tetrahydrofuran (30 mL), BH3/THF (80 mL). The resulting solution was stirred for 3 h at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 200 mL of H2O. The resulting solution was extracted with 4×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×100 mL of brine. The mixture was dried over anhydrous sodium sulfate. This resulted in 5 g (90%) of (3-chloropropyl)(2,2,2-trifluoroethyl)amine as a light yellow liquid.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[NH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]1[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1>N1C=CC=CC=1>[N:23]1[CH:24]=[CH:25][CH:26]=[C:21]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][N:15]2[S:11]([C:8]2[CH:9]=[CH:10][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=2)(=[O:13])=[O:12])[CH:22]=1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: c1cncc(C2CCCCN2)c1
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc(S(=O)(=O)N2CCCCC2c2cccnc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 842 mg portion of 4-(acetylamino)benzene sulfonyl chloride was added under ice-cooling to a pyridine solution (10 ml) of 3-(piperidin-2-yl)pyridine and stirred at room temperature for 2 hours. The solvent was concentrated under a reduced pressure, and the thus obtained residue was mixed with ethyl acetate and then washed with water, 1 M hydrochloric acid and saturated brine. This was dried with anhydrous sodium sulfate and then concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography using chloroform:methanol (98:2) as the elution solvent, thereby obtaining 1.00 g of N-(4-{[2-(pyridin-3-yl)piperidin-1-yl]sulfonyl}phenyl)acetamide as a yellow foamy substance. FAB-MS (Pos): 360 [M+H]+.
Reaction SMILES: C(OC([NH:8][C@:9]([CH3:28])([CH:19]=[CH:20][C:21]1[N:22]([CH2:26][CH3:27])[CH:23]=[CH:24][CH:25]=1)[CH2:10][O:11][C:12](=[O:18])CCCCC)=O)(C)(C)C.[OH-].[Na+].CC(C)([O-])C.[K+]>O1CCCC1.CO.C(O)(=O)C.C(OCC)(=O)C.O>[CH3:28][C@@:9]1([CH:19]=[CH:20][C:21]2[N:22]([CH2:26][CH3:27])[CH:23]=[CH:24][CH:25]=2)[CH2:10][O:11][C:12](=[O:18])[NH:8]1
Reactant: CCCCCC(=O)OC[C@@](C)(C=Cc1cccn1CC)NC(=O)OC(C)(C)C
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CC(=O)O
Product: CCn1cccc1C=C[C@]1(C)COC(=O)N1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86.8 %

Procedure:
(2R)-2-t-Butoxycarbonylamino-2-methyl-4-(1-ethylpyrrol-2-yl)-1-n-hexanoyloxy-3-butene (11.7 g, 29.8 mmol) obtained in Reference example 3 (3b) was dissolved in a mixture of tetrahydrofuran (40 mL) and methanol (40 mL) and a 2N aqueous sodium hydroxide solution (40 mL) was added thereto, followed by stirring of the mixture at room temperature for 1 hour and 30 minutes. Acetic acid (1.5 mL) was added to the reaction mixture to stop the reaction and water and ethyl acetate were added thereto to separate it. The thus obtained organic phase was separated, washed with water and a saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure to obtain a crude product (8.7 g). A solution of potassium t-butoxide (4.0 g, 35.6 mmol) in tetrahydrofuran (30 mL) was added to a solution of the crude product (8.7 g) in tetrahydrofuran (100 mL) under ice-cooling over 10 minutes, followed by stirring of the mixture at the same temperature for 1 hour. Acetic acid (2 mL) was added to the reaction mixture to neutralize it, and the mixture was concentrated under reduced pressure and water and ethyl acetate were added thereto to separate it. The thus obtained organic phase was washed with a saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate, 3:2) to obtain the title compound (5.7 g, yield: 86%).
Reaction SMILES: S([O-])(O[O-])(=O)=[O:2].[K+].[K+].[CH3:9][N:10]1[C:15](=[O:16])[C:14]2[C:17]([S:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[C:18]([CH2:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:24]=[CH:23][CH:22]=3)[S:19][C:13]=2[N:12]([CH2:39][CH:40]([CH3:42])[CH3:41])[C:11]1=[O:43].C(=O)(O)[O-].[Na+]>CO.O1CCCC1.O>[CH3:9][N:10]1[C:15](=[O:16])[C:14]2[C:17]([S:31]([CH2:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[O:2])=[C:18]([CH2:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:24]=[CH:23][CH:22]=3)[S:19][C:13]=2[N:12]([CH2:39][CH:40]([CH3:41])[CH3:42])[C:11]1=[O:43]
Reactant: COC(=O)CCCSc1c(Cc2cccc3ccccc23)sc2c1c(=O)n(C)c(=O)n2CC(C)C
Reactant: O=S(=O)([O-])O[O-]
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)CCCS(=O)c1c(Cc2cccc3ccccc23)sc2c1c(=O)n(C)c(=O)n2CC(C)C
Reaction time: 1 h
Yield: 315.3 %

Procedure:
Potassium peroxymonosulfate (0.163 g) was added to a stirred suspension of methyl 4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]butanoate (0.246 g) in methanol (3 ml), tetrahydrofuran (3 ml) and water (3 ml). After 1 hour, the reaction mixture was poured into saturated aqueous sodium bicarbonate solution (20 ml) and extracted with ethyl acetate (2×20 ml) The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography eluting with hexane:ethyl acetate (1:1) followed by trituration with ethyl acetate/hexane to give the title compound (0.80 g)
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9](C)[C:10]([C:11]#[N:12])=[C:6]2[N:5]=[C:4]([CH3:14])[C:3]=1[CH2:15][CH2:16]Cl.[C:18]([NH2:22])([CH3:21])([CH3:20])[CH3:19].[Br-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C.C(O)C.C(N(CC)CC)C>[C:18]([N:22]1[C:2]2[N:7]3[N:8]=[CH:9][C:10]([C:11]#[N:12])=[C:6]3[N:5]=[C:4]([CH3:14])[C:3]=2[CH2:15][CH2:16]1)([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)N
Reactant: Cc1nc2c(C#N)c(C)nn2c(Cl)c1CCCl
Agent: O=C([O-])[O-]
Agent: [Br-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: CCC(C)=O
Product: Cc1nc2c(C#N)cnn2c2c1CCN2C(C)(C)C
Yield: 78.5 %

Procedure:
(ii-2) A mixture of 7.0 g (0.026 mol) of Compound (VI) [R2 =CH3, R3 =CN], 6 ml of triethylamine, 15 ml of tert-butylamine, 0.1 g of sodium bromide micro-powder, 2.8 g of anhydrous sodium carbonate or potassium carbonate, 30 ml of anhydrous ethanol, and 100 ml of methyl ethyl ketone was reacted at 95° C. in an oil bath for 8 hours while stirring. The reaction solution was filtered while it was warm. The filtrate was purified using chromatography according to the same method as above to obtain Compound (I) [R1 =C(CH3)3, R2 =CH3, R3 =CN] at a yield of 78.5%.
Reaction SMILES: NC1C=CC(C([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=O)=CC=1.CC1OC(OC2C3C(=C(O)C4C(=O)C5C=CC=C(OC)C=5C(=O)C=4C=3O)CC(O)(C(CO)=O)C2)CC(N2C(C#N)COCC2)C1O.BrCCO>CN(C)C1C=CN=CC=1.C(O)(C)C>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][CH2:14][N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:17][CH:18]=1
Reactant: Nc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1
Agent: CN(C)c1ccncc1
Agent: COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)CC(O)(C(=O)CO)CC3OC1CC(N2CCOCC2C#N)C(O)C(C)O1
Agent: OCCBr
Solvent: CC(C)O
Product: Clc1ccc(CCN2CCNCC2)cc1

Procedure:
6 g of 1-(4-aminobenzoyl)-4-[2-(4-chlorophenyl)ethyl]-piperazine (see EP-A-489 690, Example 3), 2.4 g of 2-bromoethanol and 0.6 g of 4-dimethylaminopyridine are suspended in 80 ml of isopropanol and boiled at reflux for 22 hours, then concentrated by evaporation and partitioned between methylene chloride and 1N sodium hydroxide solution. The organic phase is washed with water, dried and concentrated by evaporation. The oily material is chromatographed over 150 g of silica gel. Elution with methylene chloride/methanol (100:4 and 100:5) yields 1-[4-N-(2-hydroxyethyl)-amino]-benzoyl]-4-[2-(4-chlorophenyl)-ethyl]-piperazine, m.p. 94°-95°.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH2:6])([CH3:5])[CH3:4].[CH3:7][N:8]([CH3:13])[S:9](Cl)(=[O:11])=[O:10]>CCOCC>[CH3:4][C:3]([NH2:6])([CH3:5])[CH2:2][NH:1][S:9]([N:8]([CH3:13])[CH3:7])(=[O:11])=[O:10]
Reactant: CC(C)(N)CN
Reactant: CN(C)S(=O)(=O)Cl
Solvent: CCOCC
Product: CN(C)S(=O)(=O)NCC(C)(C)N
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 60.4 %

Procedure:
A mixture of 30.7 g (0.35 mol) of 1,2-diamino-2-methylpropane, 150 ml of ether and 50 ml of trienthylamine was cooled to 0° C. and 20 g (0.14 mol) of dimethylsulfamoyl chloride was added slowly. The reaction mixture was stirred for 30 minutes and evaporated to dryness. The residue was mixed with water, basified with K2CO3 and evaporated to dryness. Acetone was added and the mixture was filtered. Evaporation of the filtrate gave a solid which recrystallized from toluene to give 16.5 g (60.3%) of product, mp 77°-78° C. The NMR and IR were consistent with the assigned structure.
Reaction SMILES: C([O:3][C:4](=O)[CH:5]([O:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2OCC[O:15]2)=[CH:10][C:9]=1[N+:19]([O-])=O)[CH3:6])C.O>C(O)(=O)C.[Fe]>[CH:14]([C:11]1[CH:12]=[CH:13][C:8]2[O:7][CH:5]([CH3:6])[C:4](=[O:3])[NH:19][C:9]=2[CH:10]=1)=[O:15]
Reactant: CCOC(=O)C(C)Oc1ccc(C2OCCO2)cc1[N+](=O)[O-]
Agent: [Fe]
Solvent: O
Solvent: CC(=O)O
Product: CC1Oc2ccc(C=O)cc2NC1=O
Reaction time: 2 h
Yield: 97.2 %

Procedure:
28.8 g of pulverized iron is added in portions to 34 g of 2-(4-(1,3-dioxolan-2-yl)-2-nitrophenoxy)propionic acid ethyl ester in 360 ml of glacial acetic acid with 80 ml of water while being cooled in an ice bath. The mixture is hot. After 2 hours, it is poured onto 1 l of water, extracted with ethyl acetate, and the organic phase is washed with brine. It is dried with magnesium sulfate and concentrated by evaporation. 20.3 g of brownish solid results.
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:22]=1[CH2:31][C:32]([O:34][CH3:35])=[O:33].CCN(C(C)C)C(C)C.[CH2:45]([Si:47]([C:52]#[CH:53])([CH2:50][CH3:51])[CH2:48][CH3:49])[CH3:46]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:48]([Si:47]([C:45]#[C:46][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:22]=1[CH2:31][C:32]([O:34][CH3:35])=[O:33])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH3:49]
Reactant: COC(=O)Cc1c(Br)cccc1C(F)(F)F
Reactant: C#C[Si](CC)(CC)CC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC[Si](C#Cc1cccc(C(F)(F)F)c1CC(=O)OC)(CC)CC
Temperature: 90 °C

Procedure:
A mixture of CuI (0.005 g, 0.03 mmol), PdCl2(PPh3)2 (0.009 g, 0.01 mmol), PPh3 (0.017 g, 0.065 mmol) and methyl 2-(2-bromo-6-(trifluoromethyl)phenyl)acetate (A91) (0.213 g, 0.717 mmol) in DMF (2.0 mL) was degassed with nitrogen for several minutes before the addition of DIPEA (2.00 mL, 11.5 mmol) and (triethylsilyl)acetylene (0.50 mL, 2.8 mmol). The resulting mixture was then degassed with nitrogen before heating under microwave irradiation at 90° C. for 2×20 minutes. The volatiles were evaporated under reduced pressure and the residue purified using silica gel column chromatography (0-10% EtOAc in petroleum benzine 40-60° C.) to give a mixture of product and starting material. To this material, CuI (0.013 g, 0.068 mmol), PdCl2(PPh3)2 (0.013 g, 0.019 mmol), PPh3 (0.030 g, 0.114 mmol), DMF (4.0 mL), DIPEA (2.00 mL, 11.5 mmol) and (triethylsilyl)acetylene (0.50 mL, 2.8 mmol) were added. The resulting mixture was heated at 100° C. for 30 minutes then concentrated under reduced pressure and the residue purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 5-10% EtOAc in petroleum benzine 40-60° C.) to give the title compound A92 (0.175 g, 69%); 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=7.7 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.35 (m, 1H), 4.09 (m, 2H), 3.68 (s, 3H), 1.03 (t, J=7.9 Hz, 9H), 0.67 (q, J=7.9 Hz, 6H).
Reaction SMILES: [C:1]1(B(O)O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Br[C:15]1[C:29]([N+:30]([O-:32])=[O:31])=[C:28]2[C:33]3[C:24](=[CH:25][CH:26]=[CH:27]2)[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]=3[CH:16]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[C:1]1([C:15]2[C:29]([N+:30]([O-:32])=[O:31])=[C:28]3[C:33]4[C:24](=[CH:25][CH:26]=[CH:27]3)[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]=4[CH:16]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: OB(O)c1cccc2ccccc12
Reactant: O=[N+]([O-])c1c(Br)cc2c3c(cccc13)-c1ccccc1-2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: COCCOC
Product: O=[N+]([O-])c1c(-c2cccc3ccccc23)cc2c3c(cccc13)-c1ccccc1-2
Temperature: 25 °C
Yield: 61.8 %

Procedure:
Under an argon atmosphere, 8.53 g of 1-naphthalene boronic acid, 14.7 g of 2-bromo-3-nitrofluoranthene, 1.04 g of tetrakistriphenylphosphine palladium(0), 70 mL of 1,2-dimethoxyethane, 70 mL of toluene, and 70 mL of a 2 M aqueous solution of sodium carbonate were charged in a flask, and the resultant mixture was refluxed for 8 h under heating and stirring. After cooling to room temperature, the reaction solution was extracted with toluene and then the aqueous layer was removed. The organic layer was washed with a saturated saline, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to obtain 10.4 g of 2-(1-naphthyl)-3-nitrofluoranthene.
Reaction SMILES: C(OC([C:8]1[C:9]2[NH:13][C:12]([C:14](C(OCCCC)=O)=[C:15]3[N:45]=[C:18]([C:19](C(OCCCC)=O)=[C:20]4[NH:37][C:23](=[C:24](C(OCCCC)=O)[C:25]5[CH:26]=[CH:27][C:28]=1[N:29]=5)[CH:22]=[CH:21]4)[CH:17]=[CH:16]3)=[CH:11][CH:10]=2)=O)CCC>CN(C=O)C>[C:9]12[CH:8]=[C:28]3[N:29]=[C:25]([CH:26]=[CH:27]3)[CH:24]=[C:23]3[NH:37][C:20]([CH:21]=[CH:22]3)=[CH:19][C:18]3=[N:45][C:15]([CH:16]=[CH:17]3)=[CH:14][C:12]([NH:13]1)=[CH:11][CH:10]=2
Reactant: CCCCOC(=O)c1c2nc(c(C(=O)OCCCC)c3ccc([nH]3)c(C(=O)OCCCC)c3nc(c(C(=O)OCCCC)c4ccc1[nH]4)C=C3)C=C2
Solvent: CN(C)C=O
Product: C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)[nH]5)C=C4)[nH]3
Temperature: 145 °C
Reaction time: 2 h
Yield: 6.4 %

Procedure:
A solution of porphyrin 40 (355 mg, 0.50 mmol) and MnCl2 (318 mg, 2.53 mmol) in anhydrous DMF (50 mL) was magnetically stirred and heated to 145° C. for 1 h then exposed to a stream of air for 2 h. The reaction mixture was cooled to room temperature overnight under a stream of air. Evaporation of DMF provided a crude solid mixture which was adsorbed onto silica gel (2 g). Purification by column chromatography (gradient elution with 0-5% MeOH/CH2Cl2) provided porphyrins 41 (170 mg) and 42 (10 mg) as solids. For porphyrin 41: mp 200-210° C.; UV-vis λmax=456.0 nm, ε=1.4×105 L/cm-mol; FAB MS m/z=763 [C40H44MnN4O8]+. For porphyrin 42: mp 200-205° C.; UV-vis λmax=459.5 nm, ε=7.2×104 L/cm-mol; FAB MS m/z=707, [C36H36MnN4O8]+.