Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:19])[N:10]([CH3:18])[C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=2)=[C:4]([F:20])[CH:3]=1.[Cl:21][S:22](O)(=[O:24])=[O:23]>>[Cl:1][C:2]1[C:7]([S:22]([Cl:21])(=[O:24])=[O:23])=[CH:6][C:5]([C:8]2[C:9](=[O:19])[N:10]([CH3:18])[C:11]([C:14]([F:16])([F:17])[F:15])=[CH:12][CH:13]=2)=[C:4]([F:20])[CH:3]=1
Reactant: O=S(=O)(O)Cl
Reactant: Cn1c(C(F)(F)F)ccc(-c2ccc(Cl)cc2F)c1=O
Product: Cn1c(C(F)(F)F)ccc(-c2cc(S(=O)(=O)Cl)c(Cl)cc2F)c1=O
Temperature: 100 °C
Reaction time: 5 h
Yield: 85.9 %

Procedure:
2.9 g (9.5 mmol) of 3-(4-chloro-2-fluorophenyl)-1-methyl-6-trifluoromethyl-2(1H)-pyridone was dissolved in 70 g of chlorosulfonic acid, followed by heating and stirring at 100° C. for 5 hours. After cooling, the mixture was gradually dropwise added to ice water, followed by extraction with ethyl acetate. After washing with water and a saturated sodium hydrogencarbonate aqueous solution, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure. Then, the obtained crude crystals were washed with n-hexane to obtain 3.3 g (yield: 86%) of the desired product. Melting point: 77-78° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH2:27])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].Br[C:29]1[CH:34]=[C:33]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:32]=[CH:31][N:30]=1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:29]4[CH:34]=[C:33]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH:32]=[CH:31][N:30]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: Brc1cc(-c2ccccc2)ccn1
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4N)cc3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cc(-c5ccccc5)ccn4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 68, Step 2, using 1-[4′-(4-amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and 2-bromo-4-phenyl-pyridine.
Reaction SMILES: [CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[C:3]([CH3:8])[CH:2]=1.C([Mg]Br)C.C1(C)C=CC=CC=1.[CH2:20]=[O:21]>C1COCC1.CN1CCCN(C)C1=O>[OH:7][C:6]1[CH:5]=[CH:4][C:3]([CH3:8])=[CH:2][C:1]=1[CH:20]=[O:21]
Reactant: Cc1ccc(O)cc1
Reactant: C=O
Agent: CC[Mg]Br
Solvent: CN1CCCN(C)C1=O
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Cc1ccc(O)c(C=O)c1
Yield: 104.4 %

Procedure:
p-Cresol (100 g) in dry THF (100 ml) was added over 30 minutes dropwise to a mechanically stirred, freshly prepared solution of ethyl magnesium bromide [magnesium (25.0 g) and bromoethane (75 ml)] in THF (500 ml) under nitrogen at a rate which maintained a slow reflux. After a further 30 mins toluene (1.21) was added, followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (125 ml), and paraformaldehyde (70 g). The mixture was then heated at reflux for 16 h. The mixture was concentrated by distillation and aqueous hydrochloric acid (2M, 600 ml) then added. Water (600 ml) was added and the mixture filtered through "hyflo", dried and concentrated in vacuo to give a brown oil. The oil was steam distilled and the product extracted from the distillate with ether (1 liter). The organic extract was dried and concentrated in vacuo to give a pale yellow slurry which was triturated with ether at -10° C. to give the title compound as colourless needles, (131.4 g).
Reaction SMILES: [CH:1]([O:4][C:5]([C:7]1[C:12](=[O:13])[N:11]2[C:14]([CH2:24][N:25]([CH3:33])[CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=3)[N:16]=[C:10]2[N:9]([CH2:34][C:35]2[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=2[F:42])[CH:8]=1)=[O:6])([CH3:3])[CH3:2].N1C=CC=CC=1.[CH2:49]([N:51]=[C:52]=[O:53])[CH3:50]>C1COCC1>[CH:1]([O:4][C:5]([C:7]1[C:12](=[O:13])[N:11]2[C:14]([CH2:24][N:25]([CH3:33])[CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:15]([C:17]3[CH:18]=[CH:19][C:20]([NH:23][C:52]([NH:51][CH2:49][CH3:50])=[O:53])=[CH:21][CH:22]=3)[N:16]=[C:10]2[N:9]([CH2:34][C:35]2[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=2[F:42])[CH:8]=1)=[O:6])([CH3:3])[CH3:2]
Reactant: CCN=C=O
Reactant: CC(C)OC(=O)c1cn(Cc2c(F)cccc2F)c2nc(-c3ccc(N)cc3)c(CN(C)Cc3ccccc3)n2c1=O
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCNC(=O)Nc1ccc(-c2nc3n(Cc4c(F)cccc4F)cc(C(=O)OC(C)C)c(=O)n3c2CN(C)Cc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.8 %

Procedure:
To a solution of the compound obtained in Example 32 (1.37 g, 2.40 mmol) in THF (3 ml) is added pyridine (0.5 ml) and ethyl isocyanate (0.38 ml, 4.8 mmol). Then the mixture is stirred at room temperature overnight. The reaction mixture is concentrated under reduced pressure to give the residue, which triturated with isopropyl ether to afford a crystalline solid, which is recrystallized from chloroform-isopropyl ether to afford pale yellow crystals (1.20 g, 78%).
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][S:7]([CH2:10][C:11](O)=O)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[Br:16][C:17]1[CH:24]=[CH:23][C:20](C=O)=[CH:19][CH:18]=1>>[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][S:7](/[CH:10]=[CH:11]/[C:20]2[CH:23]=[CH:24][C:17]([Br:16])=[CH:18][CH:19]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: O=C(O)CS(=O)(=O)Cc1ccc(F)cc1
Product: O=S(=O)(/C=C/c1ccc(Br)cc1)Cc1ccc(F)cc1
Yield: 82 %

Procedure:
A solution of 4-fluorobenzyl sulfonylacetic acid (0.01 mol) and 4-bromobenzaldehyde (0.01 mol) was subjected to Procedure 1, Part B. The title compound was obtained in 82% yield.
Reaction SMILES: [CH:1]1[CH:6]=C2C=CC(O)=C(C3C4C(=CC=CC=4)C=CC=3O)C2=C[CH:2]=1.CC(O)C.C([Sn](CC=C)(CC=C)CC=C)C=C.[Cl:40][CH2:41][CH2:42][C:43]([C:45]1[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=1)=[O:44]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(Cl)Cl>[Cl:40][CH2:41][CH2:42][C:43]([C:45]1[CH:46]=[CH:47][C:48]([F:51])=[CH:49][CH:50]=1)([OH:44])[CH2:6][CH:1]=[CH2:2]
Reactant: O=C(CCCl)c1ccc(F)cc1
Reactant: Oc1ccc2ccccc2c1-c1c(O)ccc2ccccc12
Agent: [Ti+4]
Agent: C=CC[Sn](CC=C)(CC=C)CC=C
Agent: CC(C)[O-]
Solvent: ClCCl
Solvent: CC(C)O
Product: C=CCC(O)(CCCl)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 22 h

Procedure:
To a solution of 1,1′-bi-2-naphthol (0.2280 g, 0.80 mmol, 0.26 equiv), CH2Cl2 (5 mL) and titanium(IV) isopropoxide (0.2243 g, 0.79 mmol, 0.26 equiv) were added 2-propanol (3.1620 g, 52.6 mmol, 17 equiv), tetraallylstannane (1.2538 g, 4.43 mmol, 1.43 equiv), and 3-chloro-1-(4-fluorophenyl)propan-1-one (0.5760 g, 3.09 mmol, 1.0 equiv) successively. The reaction mixture was stirred at rt under nitrogen for 22 h. The reaction was quenched with satd aq NH4Cl and extracted with EtOAc. The organic layer was dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 1-chloro-3-(4-fluorophenyl)hex-5-en-3-ol as an oil.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12](=O)[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)([CH3:4])([CH3:3])[CH3:2].[C:21]([C:25]1[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=1[NH2:27])([CH3:24])([CH3:23])[CH3:22].[OH-].[Na+]>C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12](=[N:27][C:26]1[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=1[C:21]([CH3:24])([CH3:23])[CH3:22])[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccc(C(=O)Nc2ccccc2C(C)(C)C)cc1
Reactant: CC(C)(C)c1ccccc1N
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: Cc1ccc(C(=Nc2ccccc2C(C)(C)C)Nc2ccccc2C(C)(C)C)cc1
Reaction time: 1 h
Yield: 93.3 %

Procedure:
2-tert-butyl-N-(chloro(p-tolyl)methylene)benzenamine (HS Imine II) (2.86 g, 10 mmol) was dissolved in 50 mL of toluene. 2-tert-butylaniline (1.56 mL, 10 mmol) was added dropwise at room temperature, resulting in a yellow solution, which was refluxed overnight. Toluene was removed under vacuum. Sodium hydroxide (100 mL of 0.10 M solution, 10 mmol) was added and the solution was stirred for 1 hour. The solid that deposited was extracted into 150 mL of diethylether. The ether layer was dried with MgSO4, filtered, and taken to dryness, leaving 3.72 g (93%) of white solid. The 1H NMR spectrum is complex and is consistent with a mixture of E/Z isomers.
Reaction SMILES: C[O-].[Na+].[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[CH:7][N:6]=1.[O:13]1CCOC[CH2:14]1>CO.CCOC(C)=O.O>[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=[NH:12])[O:13][CH3:14])=[CH:7][N:6]=1
Reactant: C1COCCO1
Reactant: N#Cc1ccc(Cl)nc1
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CO
Product: COC(=N)c1ccc(Cl)nc1

Procedure:
Sodium methoxide (725 mg, 13.42 mmol) was added to a solution of 2-Chloro pyridine-5-carbonitrile (1.8 g, 13.04 mmol) in MeOH:dioxane (40 ml, 1:1) at 0° C., then stirred for 30 minutes at 0° C., and 1 hour at room temperature. The reaction was diluted with EtOAc (200 ml) and H2O (100 ml), organic layer separated, dried over Na2SO4, filtered and solvent evaporated to yield title compound 1BX as a white solid (2.6 g, 100%) MS (MH 171)
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.C([Li])(C)(C)C.CN1CCCN(C)C1=O.Br[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][O:30][Si](C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[S:3]1[CH:4]=[CH:5][CH:6]=[C:2]1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][OH:30]
Reactant: Brc1cccs1
Reactant: CC(C)(C)[Si](C)(C)OCCCCCCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CN1CCCN(C)C1=O
Product: OCCCCCCCCc1cccs1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 2-bromothiophene (0.341 g, 2.09 mmol) in tetrahydrofuran (30 ml) under argon at -78° was added t-butyl lithium (2.53 ml of a 1.7M solution) followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.268 g, 2.09 mmol). To this mixture was added 1-bromo-8-t-butyldimethylsiloxyoctane (0.615 g, 1.90 mmol in tetrahydrofuran (10 ml). After gradual warming followed by stirring at room temperature for 18 hours, the mixture was concentrated, taken up in ethyl ether and washed consecutively with cold 10% hydrochloric acid, saturated sodium bicarbonate, water, saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to give a yellow oil. To this residue in tetrahydrofuran (20 ml) at 0° was added tetrabutylammonium fluoride (8.4 ml of a 1.0M solution). After stirring for 16 hours at room temperature the mixture was concentrated, taken up in ethyl ether and washed with 10% hydrochloric acid, saturated sodium bicarbonate, water, saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to give a yellow oil. Further purification by flash chromatography (silica, 30% ethyl acetate/hexane) give the desired alcohol.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].N1C=CC=CC=1.[OH:11][C:12]1[CH:20]=[CH:19][C:15]([CH2:16][CH2:17][Br:18])=[CH:14][CH:13]=1>C(Cl)Cl.O>[C:1]([O:11][C:12]1[CH:20]=[CH:19][C:15]([CH2:16][CH2:17][Br:18])=[CH:14][CH:13]=1)(=[O:3])[CH3:2]
Reactant: Oc1ccc(CCBr)cc1
Reactant: CC(=O)Cl
Solvent: O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)Oc1ccc(CCBr)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Acetyl chloride (2.01 g, 1.82 mL. 25.6 mmol) was added to a stirred solution of pyridine (2.02 g, 2.07 mL, 25.6 mmol) and 4-hydroxyphenethyl bromide (856.5 mg, 4.26 mmol) in dry CH2Cl2 (17 mL) and the reaction was stirred at room temperature for 2 h. The reaction mixture was diluted with water (20 mL) and extracted with CH2Cl2 (2×40 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to afford 4-(2-bromoethyl)phenyl acetate. 1H NMR (500 MHz, CHCl3): δ 7.22 (d, J=8.3 Hz, 2 H); 7.04 (d, J=8.3 Hz, 2 H); 3.55 (t, J=7.6 Hz, 2 H); 3.16 (t, J=7.6 Hz, 2 H); 2.29 (s, 3 H).
Reaction SMILES: [OH-].[Na+].[N+:3]([C:6]1[CH:23]=[CH:22][CH:21]=[CH:20][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([O:18]C)=[O:17])=[CH:11][CH:10]=1)([O-:5])=[O:4].O.S([O-])(O)(=O)=O.[K+]>O1CCCC1.CO>[N+:3]([C:6]1[CH:23]=[CH:22][CH:21]=[CH:20][C:7]=1[O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:13][CH:14]=1)([O-:5])=[O:4]
Reactant: COC(=O)Cc1ccc(Oc2ccccc2[N+](=O)[O-])cc1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)Cc1ccc(Oc2ccccc2[N+](=O)[O-])cc1
Temperature: 40 °C
Reaction time: 1 h
Yield: 72 %

Procedure:
Aqueous 1 N sodium hydroxide solution (41.7 ml, 41.7 mmols) was added to a solution of methyl 4-(2-nitrophenoxy)phenylacetate (2.7 g, 9.3 mmols) in tetrahydrofuran (50 ml) and methanol (50 ml). The resulting mixture was stirred at 40° C. for 1 hour. Water and potassium hydrogensulfate (5.68 g, 41.7 mmols) were added to the reaction mixture, which was then extracted with ethyl acetate. The extract was washed with water, and then dried with anhydrous magnesium sulfate. This was concentrated under reduced pressure, and the resulting solid was recrystallized from ethyl acetate/hexane to give a crystal of 4-(2-nitrophenoxy)phenylacetic acid (1.83 g, 71.8%).
Reaction SMILES: [CH:1]([C:3]1[CH:12]=[N:11][C:6]2=[N:7][CH:8]=[CH:9][N:10]=[C:5]2[CH:4]=1)=C.CC([OH:17])(C)C.I([O-])(=O)(=O)=O.[Na+]>O1CCOCC1.O.O=[Os](=O)(=O)=O>[N:10]1[CH:9]=[CH:8][N:7]=[C:6]2[N:11]=[CH:12][C:3]([CH:1]=[O:17])=[CH:4][C:5]=12
Reactant: C=Cc1cnc2nccnc2c1
Reactant: CC(C)(C)O
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: O=Cc1cnc2nccnc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95 %

Procedure:
7-Vinyl-pyrido[2,3-b]pyrazine (68 mg, 0.43 mmol) was dissolved in dioxane (4 ml) and water (5 ml). OsO4 (0.227 ml of a 2.5% t-BuOH solution, 0.024 mmol) was added, followed by sodium periodate (276 mg, 1.3 mmol). The reaction mixture was allowed to stir at room temperature. After 2 h, the reaction was judged complete by TLC, and the reaction mixture was partitioned between ethyl acetate and brine. The brine was removed and washed one additional time with ethyl acetate. The combined ethyl acetate extracts were washed again with brine, dried using MgSO4, and concentrated under vacuum to yield the title product (65 mg, 95%) as a dark, nearly black, solid. 1H NMR (DMSO-d6): δ=10.37 (s, 1H), 9.55 (d, 1H, J=2.2 Hz,), 9.28 (d, 1H, J=1.7 Hz), 9.21 (d, 1H, J=1.7 Hz), 9.10 (d, 1H, J=2.2 Hz). Calculated mass=159.15, [M+H]+=160. HPLC Method D: 97.5% @ 210-370 nm; 97.9% @ 318 rm; RT=2.4 min.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@H:16]([O:27][N:28]2C(=O)C3C(=CC=CC=3)C2=O)[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN>O1CCCC1.CO.C(OCC)(=O)C>[NH2:28][O:27][C@@H:16]([CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:14][CH:13]=1)[C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18]
Reactant: O=C(OCc1ccccc1)[C@H](Cc1ccc(OCc2ccccc2)cc1)ON1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: NO[C@@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixed solution of (S)-benzyl 3-(4-(benzyloxy)phenyl)-2-(1,3-dioxoisoindolin-2-yloxy)propanoate (Compound XXVIII-1) 15.02 g (29.6 mmol) in tetrahydrofuran 60 ml and methanol 60 ml, hydrazine monohydrate 4.31 ml (88.8 mmol) was added and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate 500 ml and washed with saturated sodium bicarbonate solution 200 ml, water 200 ml and brine 200 ml. The organic phase was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound, which was used without further purification.
Reaction SMILES: [Br:1][C:2]([F:7])([F:6])[C:3](Cl)=[O:4].[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[I:28])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C>ClCCl>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([N:21]([C:3](=[O:4])[C:2]([Br:1])([F:7])[F:6])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[I:28])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]
Reactant: O=C(Cl)C(F)(F)Br
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2ccccc2I)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(N(C(=O)C(F)(F)Br)c2ccccc2I)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.6 %

Procedure:
Bromodifluoroacetyl chloride (0.800 g, 4.1 mmol) was added dropwise to a cooled (0° C.) solution of 4-(2-Iodophenylamino)piperidine-1-carboxylic acid tert-butyl ester (1.500 g, 3.7 mmol) and triethylamine (1.0 mL, 7.1 mmol) in dichloromethane (20 mL). The cooling bath was removed 30 minutes after the addition of all reagents. The reaction mixture was stirred at ambient temperature for 1 hour, then diluted with ethyl acetate, washed with water and brine, dried over anhydrous Na2SO4 and concentrated. Purification of the residue by flash chromatography to afford 4-[(2-bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester (1.730 g, 83%). 1H NMR (300 MHz, CDCl3) δ 7.88 (dd, J=1.2 and 7.8 Hz, 1H), 7.41-7.06 (m, 3H), 4.45-4.37 (m, 1H), 4.17-4.03 (m, 2H), 2.81-2.64 (m, 2H), 2.18-2.12 (m, 1H), 1.89-1.84 (m, 1H), 1.59-1.52 (m, 1H), 1.40 (s, 9H), 1.25-0.98 (m, 1H).
Reaction SMILES: [S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:10][C:11]1[CH:22]=[CH:21][C:14]2[C:15]([CH2:18][CH2:19][OH:20])=[CH:16][O:17][C:13]=2[CH:12]=1.CCN(C(C)C)C(C)C.[O:32](S(C)(=O)=O)[S:33]([CH3:36])(=O)=[O:34]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:10][C:11]1[CH:22]=[CH:21][C:14]2[C:15]([CH2:18][CH2:19][O:20][S:33]([CH3:36])(=[O:34])=[O:32])=[CH:16][O:17][C:13]=2[CH:12]=1
Reactant: CS(=O)(=O)OS(C)(=O)=O
Reactant: OCCc1coc2cc(Oc3nc4ncccc4s3)ccc12
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CS(=O)(=O)OCCc1coc2cc(Oc3nc4ncccc4s3)ccc12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 102.5 %

Procedure:
To a solution of 2-[6-(thiazolo[4,5-b]pyridin-2-yloxy)-benzofuran-3-yl]-ethanol (0.4 g, 1.3 mmol) in DCM (13 mL) was added 4-dimethylaminopyridine (16 mg, 0.13 mmol), DIEA (0.27 mL, 1.5 mmol) and Ms2O (0.27 g, 1.5 mmol) and the resulting solution was stirred (rt, 15 min). The reaction mixture was diluted with DCM (40 mL). The organic layer was washed with saturated NH4Cl (2×50 mL), brine (2×50 mL), dried, filtered and concentrated in vacuo to provide the title compound as a clear oil (0.52 g, 100%). MS (ESI): mass calcd. for C17H14N2O5S2, 390.4; m/z found, 391.1 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:13]=[CH:12][C:6](/[CH:7]=[CH:8]/[C:9]([OH:11])=O)=[CH:5][CH:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:40][N:41]([CH3:56])[CH2:42][CH2:43][N:44]([CH3:55])[C:45]1[S:46][C:47]2[CH:53]=[C:52]([NH2:54])[CH:51]=[CH:50][C:48]=2[N:49]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[CH3:40][N:41]([CH3:56])[CH2:42][CH2:43][N:44]([CH3:55])[C:45]1[S:46][C:47]2[CH:53]=[C:52]([NH:54][C:9](=[O:11])[CH:8]=[CH:7][C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:14])=[CH:13][CH:12]=3)[CH:51]=[CH:50][C:48]=2[N:49]=1
Reactant: CN(C)CCN(C)c1nc2ccc(N)cc2s1
Reactant: O=C(O)/C=C/c1ccc(C(F)(F)F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CO
Product: CN(C)CCN(C)c1nc2ccc(NC(=O)C=Cc3ccc(C(F)(F)F)cc3)cc2s1
Yield: 21.2 %

Procedure:
Prepare according to Method A, using trans-4-trifluoromethylcinnamic acid (130 mg, 0.60 mmol), HATU (229 mg, 0.602 mmol), N2-(2-dimethylamino-ethyl)-N2-methyl-benzothiazole-2,6-diamine (100 mg, 0.400 mmol), DIEA (260 μL, 1.49 mmol), and a chromatography gradient of MeOH in CH2Cl2 (8-20%) to afford the title compound (38 mg, 21%). mass spectrum (m/e): 449.0 [M+H], 447.0 [M−H]. 1H NMR (400 MHz, DMSO-d6): δ 10.50 (s, 1H), 8.31 (d, 1H, J=2.2 Hz), 7.87-7.78 (m, 4H), 7.64 (d, 1H, J=15.8 Hz), 7.52 (dd, 1H, J=8.8, 2.2 Hz), 7.44 (d, 1H, J=8.8 Hz), 7.03 (d, 1H, J=15.8 Hz), 3.97 (dd, 2H, J=6.4, 6.4 Hz), 3.39 (dd, 2H, J=6.2, 6.2 Hz), 3.13 (s, 3H), 2.85 (s, 6H).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[C:10]1(OB(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1.CO>[C:10]1([C:2]2[N:3]=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OB(O)Oc1ccccc1
Reactant: COc1ccc(Cl)nn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1ccc(-c2ccccc2)nn1
Temperature: 85 °C
Yield: 46.6 %

Procedure:
A mixture of 3.0 g of 3-chloro-6-methoxypyridazine, 3.8 g of phenylboric acid, 2.4 g of tetrakis(triphenylphosphine)palladium(0), 160 ml of toluene, 40 ml of methanol, 80 ml of an aqueous 2 mol sodium carbonate solution and 30 ml of tetrahydrofuran was stirred under heating at 85° C. for one hour. After cooling as it was, the reaction solution was extracted with ethyl acetate. The organic phase was washed with brine and eluted with ethyl acetate through NH-silica gel (Fuji Silicia). After removing the solvent, the residue was crystallized, to give 1.8 g of the target compound.
Reaction SMILES: N1C[CH2:2]1.C1(C)C=CC(N=[N+]=[N-])=CC=1.C=CCCCCCCCC.[CH3:24][C:25]12[N:31]([C:32]3[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=3)[CH:30]1[CH2:29]CC[CH2:26]2.CC1CCCCC=1>>[CH3:26][C:25]1([CH3:24])[C:30]([CH3:29])([CH3:2])[N:31]1[C:32]1[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=1
Reactant: Cc1ccc(N2C3CCCCC32C)cc1
Reactant: C1CN1
Agent: C=CCCCCCCCC
Agent: CC1=CCCCC1
Agent: Cc1ccc(N=[N+]=[N-])cc1
Product: Cc1ccc(N2C(C)(C)C2(C)C)cc1

Procedure:
Selected control reactions following the method of the General Catalytic Reaction were attempted but without [(Me,EtTCPh)Fe(NCCH3)2](PF6)2. These reactions either gave lower yields for aziridines or almost no isolable aziridine. Two example cases are shown. 2-octyl-1-(ptolyl)aziridine. p-Tolyl azide (0.096 g, 0.72 mmol) and 1-decene (1.853 g, 13.2 mmol) were used in the General Catalytic Reaction described above yielding 0.078 g, 43% yield. 1-methyl-7-(p-tolyl)-7-azabicyclo[4.1.0]heptane. p-Tolyl azide (0.203 g, 1.53 mmol) and 1-methylcyclohexene (4.055 g, 42.2 mol) were used in the General Catalytic Reaction described above yielding 0.007 g, 2% yield.
Reaction SMILES: C([NH:5][C:6]([C:8]1[S:12][C:11]([C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:16]([OH:18])=[O:17])=[CH:10][C:9]=1[CH:23]=O)=[O:7])(C)(C)C.[NH2:25]N>C(O)(=O)C>[CH3:22][C:21]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][C:13]=1[C:11]1[S:12][C:8]2[C:6](=[O:7])[NH:5][N:25]=[CH:23][C:9]=2[CH:10]=1
Reactant: NN
Reactant: Cc1ccc(C(=O)O)cc1-c1cc(C=O)c(C(=O)NC(C)(C)C)s1
Solvent: CC(=O)O
Product: Cc1ccc(C(=O)O)cc1-c1cc2cn[nH]c(=O)c2s1
Temperature: 110 °C

Procedure:
A solution of 3-(5-(tert-butylcarbamoyl)-4-formylthiophen-2-yl)-4-methylbenzoic acid (2.30 g, 6.7 mmol) in acetic acid (20 ml) was treated with hydrazine (0.73 ml, 20 mmol) and heated to 110° C. for 8 hrs. After cooling to RT the volatiles were removed in vacuo. The residue was recrystallized from MeOH. Yield: 1.01 g. MS (ESI, pos. ion) m/z: 287 (M+1).