Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:18]=[C:17]([F:19])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:8][C@@H:7]1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:3])[CH3:2].[C:28](Cl)(=[O:38])[C:29]1[CH:37]=[CH:36][CH:35]=[C:31]([C:32](Cl)=[O:33])[CH:30]=1.C(N(CC)CC)C.[C:47]([O:55][C:56]1[C:61]([Cl:62])=[CH:60][NH:59][C:58](=[O:63])[CH:57]=1)(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>O1CCOCC1>[C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:18]=[C:17]([F:19])[C:15](=[O:16])[N:14]([C:28](=[O:38])[C:29]3[CH:37]=[CH:36][CH:35]=[C:31]([C:32]([O:63][C:58]4[CH:57]=[C:56]([O:55][C:47](=[O:54])[C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)[C:61]([Cl:62])=[CH:60][N:59]=4)=[O:33])[CH:30]=3)[C:12]2=[O:13])[CH2:8][C@@H:7]1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:3])[CH3:2]
Reactant: O=C(Oc1cc(=O)[nH]cc1Cl)c1ccccc1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cc(F)c(=O)[nH]c2=O)C[C@@H]1OCc1ccccc1
Reactant: O=C(Cl)c1cccc(C(=O)Cl)c1
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(F)c(=O)n(C(=O)c3cccc(C(=O)Oc4cc(OC(=O)c5ccccc5)c(Cl)cn4)c3)c2=O)C[C@@H]1OCc1ccccc1
Yield: 37.4 %

Procedure:
To a solution of 0.60 g of 5'-O-acetyl-3'-O-benzyl-2'-deoxy-5-fluorouridine in 30 ml of dry dioxane were added 0.42 g of isophthaloyl chloride and 1.11 ml of triethylamine, and the mixture was refluxed for 2 hours. Then 0.60 g of 4-benzoyloxy-5-chloro-2(1H)-pyridone and 1.11 ml of triethylamine were added and the resulting mixture was refluxed for 1 hour. The precipitate thus formed was filtered off, and the filtrate was concentrated. The residue was placed on a silica gel column and eluted with 40% ethyl acetate-benzene, giving 0.45 g of the title compound in a yield of 37%.
Reaction SMILES: [CH2:1]([O:4][C@H:5]1[C@H:13]([CH3:14])[O:12][C:11](=[O:15])[C@@H:10]([N:16]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:9][O:8][CH2:7][C@@H:6]1[O:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH:2]=C.C([O-])(O)=[O:37].[Na+].O=[O+][O-].CSC>CO.C(Cl)Cl>[C:19]([O:18][C:17]([N:16]([C@H:10]1[CH2:9][O:8][CH2:7][C@H:6]([O:31][CH2:32][CH2:33][CH2:34][CH3:35])[C@@H:5]([O:4][CH2:1][CH:2]=[O:37])[C@H:13]([CH3:14])[O:12][C:11]1=[O:15])[C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:23])([CH3:21])([CH3:22])[CH3:20]
Reactant: C=CCO[C@H]1[C@H](C)OC(=O)[C@@H](N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)COC[C@@H]1OCCCC
Reactant: O=C([O-])O
Agent: O=[O+][O-]
Agent: [Na+]
Solvent: CO
Solvent: CSC
Solvent: ClCCl
Product: CCCCO[C@H]1COC[C@H](N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)O[C@@H](C)[C@@H]1OCC=O
Temperature: 25 °C
Reaction time: 20 h
Yield: 907.8 %

Procedure:
A mixture of tert-butyl N-[(3S,7S,8S,9S)-8-allyloxy-7-butoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl]-N-tert-butoxycarbonylcarbamate (0.350 g, 0.698 mmol) and NaHCO3 (5.86 mg, 0.070 mmol) in MeOH (0.21 ml) and DCM (6.8 ml) was treated with ozone at −78° C. until the solution became light blue in color. The mixture was purged with nitrogen until colorless and quenched by the addition of DMS (0.10 ml, 1.40 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 20 h. The mixture was concentrated and purified by flash chromatography on (SiO2, hexanes/EtOAc gradient) to yield the title compound as a colorless oil (320 mg, 91%): IR (neat) 2934, 2876, 1743, 1706, 1367, 1253, 1121, 1096 cm−1; 1H NMR (400 MHz, CDCl3) δ 9.63 (s, 1H), 5.18 (dd, J=8.9, 3.8 Hz, 1H), 4.84 (dq, J=9.4, 6.3 Hz, 1H), 4.39 (dd, J=17.9, 0.9 Hz, 1H), 4.22 (dd, J=17.8, 0.5 Hz, 1H), 4.19 (dd, J=12.2, 3.8 Hz, 1H), 3.91-3.75 (m, 2H), 3.57-3.42 (m, 2H), 3.37 (dt, J=9.2, 6.5 Hz, 1H), 3.29 (dd, J=7.9, 6.9 Hz, 1H), 3.21 (t, J=9.0 Hz, 1H), 1.52-1.40 (m, 2H), 1.45 (s, 18H), 1.41 (d, J=6.3 Hz, 3H), 1.30-1.19 (m, 2H), 0.83 (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 200.51, 168.79, 152.61, 86.19, 83.52, 83.08, 79.09, 75.35, 72.95, 71.99, 70.03, 57.92, 32.02, 27.94, 19.29, 18.84, 13.85; HRMS-ESI (m/z) [M]+ calcd for C24H41NO10, 503.2730; found, 503.2727.
Reaction SMILES: S(Cl)([Cl:3])=O.[NH:5]1[CH2:12][CH2:11][CH2:10][C@H:6]1[C:7]([OH:9])=[O:8].[CH3:13]O>>[ClH:3].[NH:5]1[CH2:12][CH2:11][CH2:10][CH:6]1[C:7]([O:9][CH3:13])=[O:8]
Reactant: O=S(Cl)Cl
Reactant: CO
Reactant: O=C(O)[C@@H]1CCCN1
Product: COC(=O)C1CCCN1
Product: Cl
Temperature: 40 °C
Reaction time: 72 h

Procedure:
600 ml of technical-grade methanol are introduced into a multinecked flask equipped with dropping funnel and internal thermometer, with ice/sodium chloride cooling. 2.4 mol of thionyl chloride are added dropwise in such a way that the temperature of the reaction solution does not exceed -5° C. Then, 2.18 mol of proline are added in portions in the course of approximately 10 minutes. The mixture is stirred for approximately 4 hours at 40° C. and subsequently for three days at room temperature, and the solution is greatly concentrated, the residue is taken up several times in methanol to remove excess thionyl chloride, and the mixture is reconcentrated. After drying the product for several hours in a lukewarm water bath in an evacuated flask, the target compound is obtained in quantitative yield. Some of the oily crude product crystallises after being left to stand over several days.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH3:9])[CH:4]=1)#[N:2].C[O-].[Na+].[Cl-:13].[NH4+:14]>CO>[ClH:13].[CH3:9][C:5]1[CH:4]=[C:3]([C:1](=[NH:14])[NH2:2])[CH:8]=[CH:7][N:6]=1
Reactant: [Cl-]
Reactant: Cc1cc(C#N)ccn1
Reactant: [NH4+]
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Cc1cc(C(=N)N)ccn1
Product: Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A 17.2 g portion of 4-cyano-2-picoline [E. Ochiai and I. Suzuki, Pharm. Bull. (Japan), 2, 147 (1954)] was dissolved in 150 ml of methanol, 756 mg of sodium methoxide was added and the mixture was stirred overnight. A 7.9 g portion of ammonium chloride was added and the mixture was heated to reflux, then cooled to room temperature, giving 15 g of the desired compound, mp 168°-178° C.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[CH2:3][CH2:4][C:5]1[NH:9][C:8]([C:10](O)=[O:11])=[CH:7][CH:6]=1.C(Cl)(=O)C([Cl:18])=O>C(Cl)Cl.CN(C=O)C>[F:1][C:2]([F:14])([F:13])[CH2:3][CH2:4][C:5]1[NH:9][C:8]([C:10]([Cl:18])=[O:11])=[CH:7][CH:6]=1
Reactant: O=C(O)c1ccc(CCC(F)(F)F)[nH]1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1ccc(CCC(F)(F)F)[nH]1
Yield: 83.1 %

Procedure:
5-(3,3,3-trifluoropropyl)-1H-pyrrole-2-carboxylic acid (5.55 mmol, 1.15 g) in CH2Cl2 (10 ml) was treated with oxalyl chloride (16.7 mmol, 1.5 ml), then DMF (1 drop). The solution was heated to reflux for 1 h, then concentrated under reduced pressure to provide 5-(3,3,3-trifluoropropyl)-1H-pyrrole-2-carboxylic acid chloride (1.04 g). 1H NMR (CDCl3) δ 10.25 (1H, br s), 7.12 (1H, dd, J=4.0, 2.6), 6.12 (1H, dd, J=3.8, 2.7), 3.05-2.88 (2H, m), 2.59-2.41 (2H, m).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=2[C:18]([F:21])([F:20])[F:19])[CH2:4][CH2:3]1.S(S([O-])=O)([O-])=O.[Na+].[Na+]>CC(C)=O.O>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=2[C:18]([F:21])([F:19])[F:20])[CH2:4][CH2:3]1
Reactant: CN1CCN(Cc2ccc([N+](=O)[O-])cc2C(F)(F)F)CC1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: CN1CCN(Cc2ccc(N)cc2C(F)(F)F)CC1
Yield: 64.9 %

Procedure:
A suspension of 1-methyl-4-(4-nitro-2-(trifluoromethyl)benzyl)piperazine (1.23 g, 4 mmol) and sodium hydrosulfite (7.0 g, 85% pure from Aldrich, 40 mmol) in acetone and water (1:1, 20 mL) was refluxed for 3 h. Upon cooling, the volatile components (mainly acetone) were removed on rotavap, and the resulting mixture was subjected to filtration. The solid was thoroughly washed with EtOAc. The combined filtrate was extracted with n-BuOH (4×), and the combined organic layer was washed with saturated aq. NaHCO3, dried (Na2SO4), filtered, concentrated, and the resulting residue was purified by silica gel chromatography (eluted with 5% MeOH/DCM, MeOH was pre-saturated with ammonia gas) to provide 0.71 g of product as a pale yellow solid.
Reaction SMILES: [C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[CH2:10]([NH:17][C:18](=[O:21])[CH2:19]Cl)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])O.[Cs+]>CN1C(=O)CCC1>[C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[C:4]([O:6][CH2:19][C:18](=[O:21])[NH:17][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:5]
Reactant: COC(=O)/C=C/C(=O)O
Reactant: O=C(CCl)NCc1ccccc1
Agent: O=C([O-])O
Agent: [Cs+]
Solvent: CN1CCCC1=O
Product: COC(=O)/C=C/C(=O)OCC(=O)NCc1ccccc1
Yield: 52.5 %

Procedure:
Following general procedure A, methyl hydrogen fumarate (MHF) (0.50 g, 3.85 mmol) dissolved in NMP was reacted at ca. 55° C. with N-benzyl chloroacetamide (0.84 g, 4.61 mmol) in the presence of CsHCO3 (0.89 g, 4.61 mmol) to afford 0.56 g (53% yield) of the title compound (2) as a white solid after purification by mass-guided preparative HPLC and lyophilization. 1H NMR (CDCl3, 400 MHz): δ 7.36-7.26 (m, 5H), 6.94-6.88 (m, 2H), 6.19 (br s, 1H), 4.73 (s, 2H), 4.51 (d, J=5.6 Hz, 2H), 3.81 (s, 3H). MS (ESI): m/z 278.04 (M+H)+.
Reaction SMILES: CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.O1CCCCC1[O:24][CH2:25][CH2:26]/[CH:27]=[CH:28]/[C:29]1[CH:30]=[C:31]([NH:38][C:39]2[CH:44]=[CH:43][N:42]=[C:41]([NH2:45])[N:40]=2)[CH:32]=[C:33]2[C:37]=1[NH:36][N:35]=[CH:34]2>CO.CCOC(C)=O>[NH2:45][C:41]1[N:40]=[C:39]([NH:38][C:31]2[CH:32]=[C:33]3[C:37](=[C:29](/[CH:28]=[CH:27]/[CH2:26][CH2:25][OH:24])[CH:30]=2)[NH:36][N:35]=[CH:34]3)[CH:44]=[CH:43][N:42]=1
Reactant: Nc1nccc(Nc2cc(/C=C/CCOC3CCCCO3)c3[nH]ncc3c2)n1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CO
Solvent: CCOC(C)=O
Product: Nc1nccc(Nc2cc(/C=C/CCO)c3[nH]ncc3c2)n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 51 %

Procedure:
PPTS (0.019 g, 0.075 mmol) was added to a mixture of 4-{7-[(E)-4-(tetrahydro-pyran-2-yloxy)-but-1-enyl]-1H-indazol-5-ylamino}-pyrimidine-2-amine (prepared from Example #N.2.7 reacted with trans-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyoxy]-tetrahydropyran using general procedure F, 0.037 g, 0.100 mmol) in MeOH (3.0 mL). The reaction mixture was stirred at about 25° C. for about 5 hours. The reaction mixture was diluted with EtOAc (5 mL) and was washed with aqueous Na2CO3 solution (5 mL). The organic portion was evaporated under reduced pressure to afford (E)-4-[5-(2-amino-pyrimidin-4-ylamino)-1H-indazol-7-yl]-but-3-en-1-ol (0.015 g, 0.051 mmol) as an off white solid; RP-HPLC (Table 1, Method e) Rt 0.62 min; m/z: (M+H)+ 297.0.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13](=[O:15])[CH3:14])[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=3)=[N:9]2)=[CH:5][CH:4]=1.[CH3:27][N:28]([CH3:31])[CH:29]=O>O1CCCC1>[CH3:27][N:28]([CH3:31])/[CH:29]=[CH:14]/[C:13]([C:11]1[C:10]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)=[N:9][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:26][CH:25]=2)[CH:12]=1)=[O:15]
Reactant: COc1ccc(Cn2cc(C(C)=O)c(-c3cccc([N+](=O)[O-])c3)n2)cc1
Reactant: CN(C)C=O
Solvent: C1CCOC1
Product: COc1ccc(Cn2cc(C(=O)/C=C/N(C)C)c(-c3cccc([N+](=O)[O-])c3)n2)cc1
Temperature: 70 °C
Reaction time: 6 h
Yield: 94.6 %

Procedure:
460 mg (1.3 mmol) of 1-[1-(4-methoxybenzyl)-3-(3-nitrophenyl)-1H-pyrazol-4-yl]-ethanone were dissolved in 25 ml of dry tetrahydrofuran and 15 ml of dimethylformamide di-tert-butylacetale (62 mmol) were added to the resulting solution. The reaction was heated at 70° C. under stirring for 6 hours. The solvent was then evaporated in vacuo and the residue diluted with dichloromethane and washed with water. The organic layer was finally dried over sodium sulphate and evaporated, giving 500 mg (96%) of the title compound as an oil.
Reaction SMILES: Cl.[F:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:21]3[CH:22]=[N:23][N:24]([CH2:26][CH2:27][NH2:28])[CH:25]=3)=[CH:8][N:9]2[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:5][CH:4]=1.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[F:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:21]3[CH:22]=[N:23][N:24]([CH2:26][CH2:27][NH:28][S:30]([CH3:29])(=[O:32])=[O:31])[CH:25]=3)=[CH:8][N:9]2[S:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)(=[O:14])=[O:13])=[CH:5][CH:4]=1
Reactant: NCCn1cc(-c2cn(S(=O)(=O)c3ccccc3)c3cc(F)ccc23)cn1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Product: CS(=O)(=O)NCCn1cc(-c2cn(S(=O)(=O)c3ccccc3)c3cc(F)ccc23)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 120.1 %

Procedure:
To the solution of 2-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)ethanamine hydrochloride (Intermediate 19; 228 mg; 0.54 mmol) and DMAP (3 mg; 0.02 mmol) in pyridine (4 mL), was added MsCl (0.07 mL; 0.90 mmol) under nitrogen at 0° C. The reaction was warmed to r.t. and stirred overnight. The reaction mixture was concentrated and the residue was diluted with EtOAc (20 mL), washed with aqueous HCl (10 mL; 1 M), water (10 mL), brine (10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford 300 mg of the title compound as a yellow solid, which was used directly without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[C:9]=1[OH:10])[CH:5]=[O:6].C1(O)C=CC=CC=1.[CH3:21][O:22][C:23](=[O:27])[CH:24](Br)[CH3:25]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[O:6])[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[C:9]=1[O:10][CH:24]([CH3:25])[C:23]([O:22][CH3:21])=[O:27]
Reactant: COC(=O)C(C)Br
Reactant: O=Cc1cc(Cl)c(O)c([N+](=O)[O-])c1
Solvent: Oc1ccccc1
Product: COC(=O)C(C)Oc1c(Cl)cc(C=O)cc1[N+](=O)[O-]

Procedure:
Using 3-chloro-4-hydroxy-5-nitrobenzaldehyde as the phenol and methyl-2-bromopropanoate as the alkylating agent in the general procedure for alkylation of substituted-2-nitrophenols gives a light yellow oil: 1H NMR (DMSO-d6, 400 MHz): δ ppm 9.98 (s, 1H), 8.43 (d, J=1.8 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 5.08-5.15 (m, 1H), 3.62 (s, 3H), 1.57 (d, J=6.8 Hz, 3H). ESI-MS: m/z 328.1 (M+H)+.
Reaction SMILES: [C:1]1([N:7]2[C:12](=O)C3SC=C(C4C=CC=CC=4)C=3N=C2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:23][C:24]1[C:28]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)=[CH:27][S:26][C:25]=1[C:36]([O:38]C)=O.C(OCC)(OCC)OCC.[Cl:50]C1C=CC(N)=CC=1>C(O)(=O)C>[Cl:50][C:4]1[CH:5]=[CH:6][C:1]([N:7]2[C:36](=[O:38])[C:25]3[S:26][CH:27]=[C:28]([C:29]4[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=4)[C:24]=3[N:23]=[CH:12]2)=[CH:2][CH:3]=1
Reactant: Nc1ccc(Cl)cc1
Reactant: O=c1c2scc(-c3ccccc3)c2ncn1-c1ccccc1
Reactant: COC(=O)c1scc(-c2ccc(C)cc2)c1N
Solvent: CC(=O)O
Solvent: CCOC(OCC)OCC
Product: Cc1ccc(-c2csc3c(=O)n(-c4ccc(Cl)cc4)cnc23)cc1
Yield: 35 %

Procedure:
In the same manner as the synthesis of Compound 1, methyl 3-amino-4-(p -tolyl)thiophene-2-carboxylate (100 mg, 0.40 mmol), triethyl orthoformate (1 ml), 4-chloroaniline (94.4 mg, 0.74 mmol), and acetic acid (0.1 ml) were used to give 48 mg (0.14 mmol, 35% yield) of the title compound.
Reaction SMILES: O1CCCC1.[NH:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([NH2:10])=[O:9].[I-:14].CS[C:17]1[S:21][CH:20]=[CH:19][S+:18]=1>CC(C)=O.C(OCC)C>[I-:14].[S:18]1[CH:19]=[CH:20][S:21][C:17]1=[N+:6]1[CH2:13][CH2:12][CH2:11][CH:7]1[C:8](=[O:9])[NH2:10]
Reactant: NC(=O)[C@@H]1CCCN1
Reactant: CSc1scc[s+]1
Agent: [I-]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CC(C)=O
Product: NC(=O)C1CCC[N+]1=c1sccs1
Temperature: 25 °C
Yield: 52.5 %

Procedure:
To 30 ml of tetrahydrofuran, 1.6 g of proline amide was dissolved, and 2.0 g of 2-methylthio-1,3-dithiolium iodide was gradually added under stirring at room temperature. The mixture was stirred at room temperature for 1 hour, and the precipitated crystals were collected by filtration and recrystallized from acetone-ethyl ether, whereby 1.3 g (yield: 53%) of 1-(1,3-dithiol-2-ylidene)-2-carbamoylpyrrolidinium iodide (Compound No. 44) was obtained as crystals having a melting point of from 250° to 251° C.
Reaction SMILES: [NH2:1][C:2]([CH2:9][CH2:10][CH3:11])=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].C([O:14][CH:15]=[C:16]([C:22](OCC)=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])C>>[CH2:9]([C:2]1[NH:1][C:15](=[O:14])[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:22][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:10][CH3:11]
Reactant: CCCC(N)=CC(=O)OCC
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Product: CCCc1[nH]c(=O)c(C(=O)OCC)cc1C(=O)OCC
Temperature: 20 °C

Procedure:
62.8 g (0.4 mol) of ethyl 3-amino-hex-2-en-oate and 86.4 g (0.4 mol) of diethyl ethoxymethylenemalonate are stirred at 100° C. for 40 hours. The mixture is cooled to 20° C. and the solid is filtered off with suction and recrystallised from ethanol.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]([S:7]([F:12])([F:11])([F:10])([F:9])[F:8])[CH:4]=[C:3]([C:13]([OH:15])=O)[CH:2]=1.O=S(Cl)[Cl:18]>>[F:8][S:7]([F:12])([F:11])([F:10])([F:9])[C:5]1[CH:4]=[C:3]([CH:2]=[CH:1][CH:6]=1)[C:13]([Cl:18])=[O:15]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cccc(S(F)(F)(F)(F)F)c1
Product: O=C(Cl)c1cccc(S(F)(F)(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 3-(pentafluorothio)benzoic acid (Apollo Scientific, 0.42 g, 1.7 mmol) and SOCl2 (1.2 mL, 16.9 mmol) was warmed to reflux and was allowed to stir for 2 hours. The mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was dissolved in toluene (5 mL) and was concentrated under reduced pressure. This dilution with toluene and concentration was repeated two additional times to remove residual thionyl chloride and afford 3-(pentafluoro-λ6-sulfanyl)benzoyl chloride that was used directly below.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]([F:28])([F:27])[F:26])(=[O:18])=[O:17])=[N:11][CH:12]=[CH:13][N:14]=2)=[CH:5][CH:4]=1.[Cl:29][C:30]1[CH:31]=[C:32]([OH:36])[CH:33]=[CH:34][CH:35]=1>>[Cl:29][C:30]1[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=1)[O:36][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]([F:27])([F:26])[F:28])(=[O:17])=[O:18])=[N:11][CH:12]=[CH:13][N:14]=2)=[CH:5][CH:4]=1
Reactant: O=S(=O)(Nc1nccnc1-c1ccc(CCl)cc1)c1ccccc1C(F)(F)F
Reactant: Oc1cccc(Cl)c1
Product: O=S(=O)(Nc1nccnc1-c1ccc(COc2cccc(Cl)c2)cc1)c1ccccc1C(F)(F)F
Yield: 70 %

Procedure:
Following the general method as outlined in Example 1 (Method A), starting from N-{3-[4-(chloromethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamide (Intermediate 9), and 3-chlorophenol, the title compound was isolated as a yellow solid in 70% yield (98% purity by HPLC).
Reaction SMILES: [I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][C:17](C)=[CH:16][CH:15]=2)[O:6][C:7]=1[C:8]1C=CC=CC=1.C/C(/[C:25](C)=[O:26])=N\O.COC1C=CC(C=O)=CC=1>>[I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][C:17]([O:26][CH3:25])=[CH:16][CH:15]=2)[O:6][C:7]=1[CH3:8]
Reactant: CC(=O)/C(C)=N/O
Reactant: Cc1ccc(-c2nc(CI)c(-c3ccccc3)o2)cc1
Agent: COc1ccc(C=O)cc1
Product: COc1ccc(-c2nc(CI)c(C)o2)cc1

Procedure:
Analogously to the building block synthesis of 4-iodomethyl-5-phenyl-2-p-tolyloxazole, diacetylmonoxime and 4-methoxybenzaldehyde gave 4-iodomethyl-2-(4 methoxyphenyl)-5-methyloxazole.
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=2)[CH:4]=[CH:5][N:6]=1.[N+:15]([CH2:18][CH3:19])([O-:17])=[O:16].NCCC(O)=O>C(O)CCC>[CH3:1][C:2]1[N:3]([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=[C:18]([N+:15]([O-:17])=[O:16])[CH3:19])=[CH:9][CH:8]=2)[CH:4]=[CH:5][N:6]=1
Reactant: CC[N+](=O)[O-]
Reactant: Cc1nccn1-c1ccc(C=O)cc1
Agent: NCCC(=O)O
Solvent: CCCCO
Product: CC(=Cc1ccc(-n2ccnc2C)cc1)[N+](=O)[O-]

Procedure:
Similar to example 4(a), the reaction is carried out with 66 g 4-(2-methyl-1-imidazolyl)-benzaldehyde (DE-OS No. 33 06 196), 31.7 g nitroethane, 3.2 g β-alanine and 250 ml n-butanol.
Reaction SMILES: COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:18][CH:19]=[C:20]([CH:23]=3)[CH:21]=O)[N:10]=2)=CC=1.Cl.[OH:45][CH:46]1[CH2:49][NH:48][CH2:47]1>>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:23]=[C:20]([CH2:21][N:48]3[CH2:49][CH:46]([OH:45])[CH2:47]3)[CH:19]=[N:18][C:17]=2[NH:24][C:25]2[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[N:10]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C=O)cnc3Nc3ccc(OC)nc3)n2)cc1
Reactant: OC1CNC1
Agent: Cl
Product: COc1ccc(Nc2ncc(CN3CC(O)C3)cc2-c2nc(C)nc(N)n2)cn1

Procedure:
The title compound was synthesized following an analogous procedure to Example 220 using 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (0.22 g, 0.381 mmol) and 3-hydroxyazetidine hydrochloride (Oakwood Products, Inc., West Columbia, S.C.) (0.063 g, 0.571 mmol). 1H NMR (400 MHz, CDCl3) δ 11.46 (s, 1H); 8.53 (br. s., 1H); 8.36 (d, J=2.54 Hz, 1H); 8.14 (d, J=2.15 Hz, 1H); 8.09 (dd, J=8.90, 2.64 Hz, 1H); 6.77 (d, J=8.80 Hz, 1H); 4.46-4.55 (m, 1H); 3.94 (s, 3H); 3.64 (s, 2H); 3.59 (t, J=7.73 Hz, 2H); 3.30-3.40 (m, 2H); 2.56 (s, 3H). m/z (ESI, +ve ion) 395.0 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C:3]=1[CH:4]=[CH:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C@@H:10]2[C:22]([NH:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].O.[C:30](OC(=O)C)(=[O:32])[CH3:31]>N1C=CC=CC=1>[C:30]([NH:1][C:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C:3]=1[CH:4]=[CH:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C@@H:10]2[C:22]([NH:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])(=[O:32])[CH3:31]
Reactant: CC(C)(C)NC(=O)[C@H]1CC[C@H]2[C@@H]3C=CC4=C(N)C(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)NC1=C2C=C[C@H]3[C@@H]4CC[C@H](C(=O)NC(C)(C)C)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Reaction time: 3 h
Yield: 30.4 %

Procedure:
A solution of 4-amino-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17β-carboxamide (0.9 g, 2.34 mmole) in acetic anhydride (3 mL) and pyridine (6 mL) was stirred overnight at room temperature. Water was added and the mixture was stirred for 3 hours. The solids were collected by filtration to give a brown solid which was purified by flash chromatography (hexane-50% ethyl acetate, ethyl acetate) to give 4-acetamido-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17β-carboxamide (0.29 g, 30.4%, diethyl ether-hexane). IR 3442, 3382, 1664, 1616 cm-1 ; MS (CI) m/z 427 (100%, M+ +1); (EI) m/z 426 (65%, M+), 57 (100%); 1H NMR (CDCl3) δ 0.78 (3H, s, C18 -Me), 1.13 (3H, s, C19 -Me), 1.35 (s, 3× tBu-Me's), 2.14 (s, Ac-Me), 5.13 (1H, s, NHCOBu), 6.16 (2H, s, C6 -H+C7 -H), 7.12 (1H, NHAc); 13C NMR (CDCl3) δ 124.65, 124.89, 139.95, 153.20, 168.74, 171.44, 194.93. This compound has the following structure: ##STR4##