Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:4]1[CH:10]=[CH:9][CH:8]=[C:7]([CH:11]([CH3:13])[CH3:12])[C:5]=1[NH2:6])([CH3:3])[CH3:2].Cl[C:15]1[CH:32]=[C:19]2[C:20]3[C:25]([CH2:26][CH2:27][N:18]2[C:17](=[O:33])[N:16]=1)=[CH:24][C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=3>CC(O)C>[CH:11]([C:7]1[CH:8]=[CH:9][CH:10]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5]=1[N:6]=[C:15]1[CH:32]=[C:19]2[C:20]3[C:25]([CH2:26][CH2:27][N:18]2[C:17](=[O:33])[NH:16]1)=[CH:24][C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=3)([CH3:13])[CH3:12]
Reactant: CC(C)c1cccc(C(C)C)c1N
Reactant: COc1cc2c(cc1OC)-c1cc(Cl)nc(=O)n1CC2
Solvent: CC(C)O
Product: COc1cc2c(cc1OC)-c1cc(=Nc3c(C(C)C)cccc3C(C)C)[nH]c(=O)n1CC2
Temperature: 25 °C
Yield: 78.7 %

Procedure:
2,6-Diisopropylaniline (9.62 ml, 51 mmol) and 2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one (5 g, 17 mmol) were suspended in propan-2-ol (400 ml) and heated at reflux, under nitrogen, for 4 days. After cooling to room temperature, the solution was concentrated in vacuo and the residue purified by flash column chromatography [dichloromethane/methanol (98:2-96:4)] to afford the title compound (5.8 g, 79%) as a yellow/orange solid.
Reaction SMILES: [NH2:1][CH:2]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.C[CH2:28][OH:29]>C(OCC)=O>[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH:2]([C:3]2[N:12]=[C:11]([NH:13][C:14]3[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=3)[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=2)[NH:1][CH:28]=[O:29])=[CH:25][CH:24]=1
Reactant: CCO
Reactant: Cc1cc(Nc2nc(C(N)c3ccc(F)cc3)nc3ccccc23)n[nH]1
Solvent: CCOC=O
Product: Cc1cc(Nc2nc(C(NC=O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
Temperature: 120 °C
Yield: 8 %

Procedure:
To 2-(amino(4-fluorophenyl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine from Example 45 Step B (0.1 g, 0.28 mmol) in ethyl formate (4 mL) were added TEA (0.2 mL) and EtOH (0.5 mL), and the mixture was heated to 120° C. for 30 min in a Biotage microwave reactor and then concentrated under reduced pressure. The residue was diluted with DMSO (5 mL) and purified by reverse-phase preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% HOAC/MeOH and solvent A=0.05% HOAc/H2O) to afford N-((4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methyl)formamide (8 mg, 8%). 1H NMR (300 MHz, DMSO-d6) δ 2.26 (s, 3H) 6.07 (d, 1H) 6.44 (s, 1H) 7.16 (t, 2H) 7.4-7.6 (m, 3H) 7.8 (m, 2H) 8.21 (s, 1H) 8.62 (d, 1H) 9.06 (d, 1H) 10.48 (bs, 1H) 12.17 (bs, 1H); LC-MS (ESI) m/z 377 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][C:11]([Cl:15])=[CH:10]2)=[O:5])[CH3:2].[C:22](=O)([O-])[O-].[K+].[K+].CI>CS(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:22])[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][C:11]([Cl:15])=[CH:10]2)=[O:5])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)c1[nH]c(-c2ccccc2)c2cc(Cl)ccc12
Agent: [K+]
Solvent: CS(C)=O
Solvent: CI
Product: CCOC(=O)c1c2ccc(Cl)cc2c(-c2ccccc2)n1C
Temperature: 0 °C

Procedure:
A suspension of 15 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 150 ml. of dimethylsulfoxide is treated under an atmosphere of argon at 15°-20° C. with 13.8 g. of finely ground dry potassium carbonate and 14 ml. of methyl iodide, the mixture is stirred intensively at room temperature for 1 hour and then poured on to 750 ml. of ice-water. After the addition of 35 g. of sodium chloride, the precipitated product is removed by filtration, washed with water and dissolved in methylene chloride. The organic phase is dried over sodium sulfate and evaporated. The residue crystallizes upon trituration with hexane. Recrystallization from ethanol yields 5-chloro-2-methyl-3-phenylisoindole-1-carboxylic acid ethyl ester in the form of almost colorless crystals having a melting point of 94°-96° C.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([OH:23])=O)=[CH:15]3)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH2:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH2:50][CH2:49][NH:48]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH2:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH2:50][CH2:49][N:48]1[C:21]([C:16]1[NH:17][C:18]2[C:14]([CH:15]=1)=[CH:13][C:12]([C:10]([N:7]1[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]1)=[O:11])=[CH:20][CH:19]=2)=[O:23]
Reactant: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)O)cc3c2)CC1
Reactant: c1ccc2c(c1)CCNC2
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)N4CCc5ccccc5C4)cc3c2)CC1

Procedure:
The title compound was synthesized in analogy to example 1, from 5-(4-isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid 1:1 hydrochloride, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (commercially available), 3,4-Dihydro-1H-isoquinoline (commercially available) and N,N-diisopropylethylamine in N,N-dimethylformamide to give the desired product after purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile/water/formic acid.
Reaction SMILES: [F-].[K+].[F:3][C:4]([P:10](=[O:25])(C(F)(F)C(F)(F)F)[C:11]([F:17])([F:16])[C:12]([F:15])([F:14])[F:13])([F:9])[C:5]([F:8])([F:7])[F:6].[CH2:26]([OH:29])[C:27]#[CH:28]>>[P:10]([O:29][CH2:26][C:27]#[CH:28])([C:4]([C:5]([F:6])([F:7])[F:8])([F:3])[F:9])([C:11]([C:12]([F:15])([F:14])[F:13])([F:17])[F:16])=[O:25]
Reactant: O=P(C(F)(F)C(F)(F)F)(C(F)(F)C(F)(F)F)C(F)(F)C(F)(F)F
Reactant: C#CCO
Agent: [F-]
Agent: [K+]
Product: C#CCOP(=O)(C(F)(F)C(F)(F)F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 19.5 h

Procedure:
Potassium fluoride (0.262 g; 4.5 mmol) is suspended in cooled (0° C.) tris(pentafluoroethyl)phosphine oxide (14.930 g; 37.0 mmol) in a 100 ml glass flask, and propargyl alcohol (2.055 g; 36.7 mmol) is added. The yellow reaction solution is slowly warmed (about 6 h) and stirred at room temperature for 19.5 h. Volatile components are removed in vacuo (10−3 mbar) at 0° C. After recondensation in vacuo (10−3 mbar) at room temperature, propargyl bis(pentafluoroethyl)phosphinate, (C2F5)2P(O)OCH2C≡CH, is isolated as clear and colourless liquid (7.831 g; 23.0 mmol) in a yield of 63% and a purity of 95%. The ester becomes a brown colour after a few minutes at room temperature and is therefore stored at 3° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)=[O:13])=[CH:2]1.[CH2:26](Br)[CH:27]([CH3:29])[CH3:28]>>[CH2:26]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)=[O:13])=[CH:2]1)[CH:27]([CH3:29])[CH3:28]
Reactant: COc1cc(C(=O)/C=C/c2c[nH]c3ccccc23)cc(OC)c1OC
Reactant: CC(C)CBr
Product: COc1cc(C(=O)/C=C/c2cn(CC(C)C)c3ccccc23)cc(OC)c1OC

Procedure:
Substantially the same procedure as in Example 3 was repeated using Compound 1 (1.69 g) obtained in Example 1 and isobutyl bromide (0.82 ml) to give Compound 5 (1.32 g).
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:14])[N:4]([CH:11]([CH3:13])[CH3:12])[C:5]([S:9][CH3:10])=[N:6][C:7]=1[OH:8].[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Br:1][C:2]1[C:3](=[O:14])[N:4]([CH:11]([CH3:12])[CH3:13])[C:5]([S:9][CH3:10])=[N:6][C:7]=1[O:8][CH2:20][C:19]1[CH:22]=[CH:23][C:16]([Cl:15])=[CH:17][CH:18]=1
Reactant: Clc1ccc(CBr)cc1
Reactant: CSc1nc(O)c(Br)c(=O)n1C(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CSc1nc(OCc2ccc(Cl)cc2)c(Br)c(=O)n1C(C)C
Yield: 55.3 %

Procedure:
In 20 ml of N,N-dimethylformamide were dissolved 1.0 g of 5-bromo-6-hydroxy-2-methylthio-3-i-propyl-4(3H)-pyrimidinone and 0.74 g of 4-chlorobenzylbromide, and then 1 g of potassium carbonate was added thereto. The mixture was subjected to a reaction at 80° C. for 3 hours. After allowing to cool in air, the resulting solution was poured into 50 ml of water and then extracted twice with 30 ml of ethyl ether. The ethyl ether layer was washed with water, dried over anhydrous sodium sulfate and freed of solvent by distillation under reduced pressure to give 1.25 g of a crude product. The product was purified by means of column chromatography (on silica gel, eluting with benzene) to give 0.8 g of the intended product as an oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](C2C=CC=CC=2)[C@@:9]([NH:38]C(=O)OC(C)(C)C)([C:11]2[O:12][C:13]([C:16]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[N:19]=[C:18]([N:28]([CH2:34][CH2:35][O:36][CH3:37])[CH2:29][C@@H:30]4[CH2:32][C@H:31]4[CH3:33])[CH:17]=3)=[N:14][N:15]=2)[CH3:10])=[CH:4][CH:3]=1.[C:52]([OH:58])([C:54]([F:57])([F:56])[F:55])=[O:53]>C(Cl)Cl>[NH2:38][C@:9]([C:11]1[O:12][C:13]([C:16]2[CH:17]=[C:18]([N:28]([CH2:34][CH2:35][O:36][CH3:37])[CH2:29][C@@H:30]3[CH2:32][C@H:31]3[CH3:33])[N:19]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:24])=[O:25])[CH:21]=2)=[N:14][N:15]=1)([CH3:10])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1.[C:52]([OH:58])([C:54]([F:57])([F:56])[F:55])=[O:53]
Reactant: COCCN(C[C@@H]1C[C@H]1C)c1cc(-c2nnc([C@](C)(NC(=O)OC(C)(C)C)C(c3ccccc3)c3ccc(F)cc3)o2)cc(N(C)S(C)(=O)=O)n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCN(C[C@@H]1C[C@H]1C)c1cc(-c2nnc([C@](C)(N)Cc3ccc(F)cc3)o2)cc(N(C)S(C)(=O)=O)n1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of tert-butyl [(1R)-2-(4-fluorophenyl)-1-(5-{2-{(2-methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]pyridin-4-yl}-1,3,4-oxadiazol-2-yl)-1-methyl-2-phenylethyl]carbamate (11.58 g, 17.9 mmol) in DCM (75 mL) cooled to 0° C. was added TFA (25 mL) and the reaction mixture was stirred at rt for 16 h, concentrated in vacuo, and reconcentrated several times from DCM, to give N-(4-{5-[(1R)-1-amino-2-(4-fluorophenyl)-1-methylethyl]-1,3,4-oxadiazol-2-yl}-6-{(2-methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-methylmethanesulfonamide as a TFA salt. MS M+1=547. 1H NMR (400 MHz, CD3OD) δ 7.10 (m, 5H), 7.01 (s, 1H), 3.82 (t, J=5.86 Hz, 2H), 3.64 (t, J=5.86, 2H), 3.50 (AB overlapping m, 4H), 3.39 (s, 3H), 3.35 (s, 3H), 3.18 (s, 3H), 1.88 (s, 3H), 1.05 (d, J=5.86, 3H), 0.78 (m, 2H), 0.49 (m, 1H), 0.30 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([NH:14][CH:15]([CH3:17])[CH3:16])[N:11]3[C:18](=[O:21])[NH:19][N:20]=[C:10]3[C:9]=2[C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)=[CH:4][CH:3]=1.[CH3:29]N(C=O)C.C(=O)([O-])[O-].[K+].[K+].CI>CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([NH:14][CH:15]([CH3:17])[CH3:16])[N:11]3[C:18](=[O:21])[N:19]([CH3:29])[N:20]=[C:10]3[C:9]=2[C:22]2[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=2)=[CH:4][CH:3]=1
Reactant: CC(C)Nc1nc(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2)c2n[nH]c(=O)n12
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CI
Product: CC(C)Nc1nc(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2)c2nn(C)c(=O)n12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a mixture of crude 7,8-bis(4-chlorophenyl)-5-(isopropylamino)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one, DMF (0.7 mL), and potassium carbonate (21 mg, 0.15 mmol) was added methyl iodide (213 mg, 1.5 mmol). The resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was then diluted with EtOAc, washed with water and saturated aqueous NaCl, dried (Na2SO4), and concentrated at reduced pressure. The residue was purified by preparative reverse phase HPLC to obtain 14 mg (65% over two steps) of the title compound as a light yellow solid. HPLC/MS: retention time=4.54 min, [M+H]30 =428.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[F:11][C:12]1[CH:13]=[C:14]([NH2:19])[CH:15]=[C:16]([NH2:18])[CH:17]=1.C(N(CC)CC)C>C1COCC1>[NH2:19][C:14]1[CH:15]=[C:16]([NH:18][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=2)[CH:17]=[C:12]([F:11])[CH:13]=1
Reactant: Nc1cc(N)cc(F)c1
Reactant: O=C(Cl)c1ccc(F)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Nc1cc(F)cc(NC(=O)c2ccc(F)cc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 60.1 %

Procedure:
Add slowly 4-fluorobenzoyl chloride (403 mg, 2.54 mmol) to a solution of 5-fluoro-benzene-1,3-diamine (Preparation 32 320 mg, 2.54 mmol) in triethylamine (514 mg, 0.71 mL, 5.08 mmol) and THF (10 mL) at 0° C. Stir the mixture overnight and gradually raise to room temperature. Quench the reaction with 0.1N NaOH solution, and extract the mixture with ethylacetate three times. Combine the organic layers and wash with saturated NaCl solution, dry over Na2SO4, filter and concentrate to give a solid. Purify by chromatography (silica gel, eluting with 25–40% ethylacetate in hexanes) gives 379 mg (60%) of N-(3-amino-5-fluoro-phenyl)-4-fluoro-benzamide.
Reaction SMILES: [NH:1]1CCCN1C(O)=O.CC#N.[C:12]1([N:18]=[C:19]=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(Cl)Cl>[C:12]1([NH:18][C:19]([NH2:1])=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(O)N1CCCN1
Reactant: O=C=Nc1ccccc1
Solvent: ClCCl
Solvent: CC#N
Product: NC(=O)Nc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 247.9 %

Procedure:
To a solution of azaproline VI (20.0 mg, 0.056 mmol) and TEA (9.5 pt, 0.068 mmol) in DCM (400 μL)/MeCN (750 μL) was added phenylisocyanate (7.3 μL, 0.067 mmol). The solution was stirred at rt for 16 h then concentrated in vacuo. The crude residue was purified by silica gel chromatography (ethyl acetate-hexanes) to afford 18.9 mg of phenylurea in 71% yield. LCMS (M+1): 474.84.
Reaction SMILES: [O:1]1[CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2]1.[CH3:12][C:13]([NH2:24])([CH3:23])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1>>[OH:1][CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2][NH:24][C:13]([CH3:23])([CH3:12])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1
Reactant: COc1ccc(CC(C)(C)N)cc1
Reactant: CCCCCCCCC1CO1
Product: CCCCCCCCC(O)CNC(C)(C)Cc1ccc(OC)cc1
Yield: 21.8 %

Procedure:
Using the method of Example 5, supra, 1,2-epoxydecane (204 mg, 1.0 mmol) and 1,1-dimethyl-2-(4-methoxyphenyl)-ethylamine (197 mg, 1.1 mmol) were used to prepare 73 mg of the title compound as a clear, colorless oil: GC/EI-MS, m/z (rel. int.) 214 (M−121, 100), 196 (27.8), 163 (10), 121 (2.2); 1H-NMR (CDCl3) δ 7.08 (2H, d, J=5.6), 6.83 (2H, d, J=8.6), 3.79 (3H, s), 3.53 (1H, m), 2.79 (1H, dd, J=11.7 and 2.9), 2.67 (2H, s), 2.42 (1H, dd, J=12.6 and 9.6), 1.26 (18 H, m), 1.08 (3H, s), 0.88 (3H, t, J=6.6); 13C-NMR (CDCl3) δ 158.2, 131.4, 129.8, 113.5, 77.2, 69.8, 55.2, 53.8, 47.8, 46.5, 35.1, 31.9, 29.8, 29.7, 29.6, 29.3, 26.6, 26.4, 25.7, 22.7, 14.1; FT-IR (film) cm−1 3399 (broad s), 1612, 1512, 1246, 1039, 823.
Reaction SMILES: [Na].[CH3:2][O-:3].[Na+].[O:5]1[C@H:7]2[CH2:8][C@H:9]3[C@:24]([CH3:26])([CH2:25][C@@H:6]12)[C@@H:23]1[C@H:12]([C@H:13]2[C@:20]([CH3:28])([CH2:21][C:22]1=[O:27])[C@@H:16]([C:17](=[O:19])[CH3:18])[CH2:15][CH2:14]2)[CH2:11][CH2:10]3.Cl>CO.O>[OH:3][C@@H:2]1[C@@H:6]([O:5][CH3:7])[CH2:25][C@@:24]2([CH3:26])[C@@H:9]([CH2:10][CH2:11][C@@H:12]3[C@@H:23]2[C:22](=[O:27])[CH2:21][C@@:20]2([CH3:28])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C:17](=[O:19])[CH3:18])[CH2:8]1
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]5O[C@@H]5C[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: C[O-]
Agent: Cl
Agent: [Na+]
Agent: [Na]
Solvent: O
Solvent: CO
Product: CO[C@H]1C[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CC[C@H](C(C)=O)[C@@]4(C)CC(=O)[C@@H]32)C[C@@H]1O

Procedure:
Sodium (70 mg.) was dissolved in dry methanol (5 ml.), and to the resulting solution of sodium methoxide (about 166 mg,) was added 2α,3α-epoxy-5α-pregnane-11,20-dione (100 mg). The solution was refluxed for 5 days, then water was added, and the mixture was neutralised with dilute hydrochloric acid and extracted into chloroform. The extract was dried over sodium sulphate and evaporated to a brown oil which was purified by preparative TLC in ethyl acetate/petrol (1/1). The title compound was recrystallised from ethyl acetate/petrol (21 mg).
Reaction SMILES: [OH:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([O:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][C:3]1([CH3:20])[CH3:19].C(#N)C.[CH2:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.OO>O>[CH:24]1([O:1][N:2]2[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([O:10][C:11](=[O:18])[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:4][C:3]2([CH3:20])[CH3:19])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1O
Reactant: C1CCCCC1
Agent: OO
Solvent: CC#N
Solvent: O
Product: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1OC1CCCCC1
Temperature: 56 °C
Yield: 84 %

Procedure:
A solution of 0.097 g (0.359 mmol) of ferric chloride hexahydrate in 2 ml of water is added to a mixture of 5.00 g (18.1 mmol) of 1-oxyl-4-benzoyloxy-2,2,6,6-tetramethylpiperidine, 28 ml of acetonitrile, and 19 ml of cyclohexane. The mixture is heated to 56° C. A solution of 4.70 g (69 mmol) of 50% aqueous hydrogen peroxide is added dropwise over 2.25 hours to the reaction mixture while the temperature is brought to and maintained at reflux. After the peroxide is added, the mixture is heated at reflux for 45 minutes. Work-up and purification according to the procedure of Example 5 afford 5.47 g (84% yield) of the title compound, a pale yellow syrup. GC assay is 100%.
Reaction SMILES: [C:1]([C:3]1[C:4]([O:13][CH2:14][CH2:15][OH:16])=[N:5][NH:6][C:7]=1[N:8]=[CH:9][N:10](C)C)#[N:2].[CH3:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=1)N>>[F:33][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=1)[CH2:26][O:25][C:24]1[CH:23]=[CH:22][C:20]([NH:2][C:1]2[N:10]=[CH:9][N:8]=[C:7]3[NH:6][N:5]=[C:4]([O:13][CH2:14][CH2:15][OH:16])[C:3]=23)=[CH:19][C:18]=1[CH3:17]
Reactant: CN(C)C=Nc1[nH]nc(OCCO)c1C#N
Reactant: Cc1cc(N)ccc1OCc1cccc(F)c1
Product: Cc1cc(Nc2ncnc3[nH]nc(OCCO)c23)ccc1OCc1cccc(F)c1
Yield: 57.8 %

Procedure:
The procedure described in Example 1 was repeated using N′-[4-cyano-3-(2-hydroxyethoxy)-1H-pyrazol-5-yl]-N,N-dimethylimidoformamide (2.0 g, 8.96 mmol) and 3-methyl-4-[(3-fluorobenzyl)oxy]aniline (2.5 g, 10.8 mmol) to give the title compound as a white solid (2.12 g, 58%); NMR Spectrum: 2.24 (s, 3H), 3.79 (s, 2H), 4.30 (t, 2H), 5.17 (s, 2H), 7.02 (d, 1H), 7.15 (td, 1H), 7.31 (m, 2H), 7.42 (m, 3H), 7.85 (t, 1H), 8.23 (s, 1H), 8.21 (s, 1H), 8.33 (s, 1H); Mass Spectrum: 410 (MH+).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([NH2:17])([CH3:16])[CH3:15])[N:5]=[C:4]([CH3:18])[C:3]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20].[CH3:24][CH:25]([CH3:30])[CH2:26][C:27](O)=[O:28]>>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([CH3:16])([NH:17][C:27](=[O:28])[CH2:26][CH:25]([CH3:30])[CH3:24])[CH3:15])[N:5]=[C:4]([CH3:18])[C:3]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20]
Reactant: CC(C)CC(=O)O
Reactant: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)N)c2c1N
Product: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)NC(=O)CC(C)C)c2c1N

Procedure:
Prepared as in Example 24a from ethyl 4-amino-5-(2-amino-2-methylpropoxy)-2-methylquinoline-3-carboxylate (Example 24b) and 3-methylbutanoic acid as an off-white solid (100%). MS 402 (MH+).
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][C:6](=[N:9][OH:10])[CH2:7][CH3:8])[CH3:3].CO.C[O-].[Na+].O1C[CH2:19][CH2:18][CH2:17]1.C(Br)C=C>>[CH3:1][C:2](=[CH:4][CH2:5][C:6](=[N:9][O:10][CH2:19][CH:18]=[CH2:17])[CH2:7][CH3:8])[CH3:3]
Reactant: C1CCOC1
Reactant: CCC(CC=C(C)C)=NO
Agent: C[O-]
Agent: [Na+]
Solvent: C=CCBr
Solvent: CO
Product: C=CCON=C(CC)CC=C(C)C
Temperature: 0 °C

Procedure:
A reactor was charged with 1 mole of 2-methyl-5-hydroxyimino-2-heptene, 8 moles of methanol containing 1.2 moles of sodium methylate, and 10 moles of tetrahydrofuran (THF). The mixture was cooled to 0° C., and with stirring, 1.3 moles of allyl bromide was added dropwise over 5 minutes. The mixture was stirred at room temperature for one day. The reaction mixture was concentrated, and 40 parts of methylene chloride was added. The mixture was washed with water, and the solvent was evaporated. The residue was purified by silica gel column chromatography to give 2-methyl-5-allyloxyimino-2-heptene in a yield of 80 mole %. Identification of this compound was performed by using IR, NMR and mass spectra (the same techniques were used to identify compounds appearing hereinafter).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[CH3:12][O:13][C:14](=[O:21])[CH:15]=[C:16]([NH2:20])[O:17][CH2:18][CH3:19]>C(O)(C)C>[CH3:12][O:13][C:14]([C:15]1[CH:7]([C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH:15]([C:14]([O:13][CH3:12])=[O:21])[C:16]([O:17][CH2:18][CH3:19])=[N:20][C:16]=1[NH2:20])=[O:21]
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: CCOC(N)=CC(=O)OC
Solvent: CC(C)O
Product: CCOC1=NC(N)=C(C(=O)OC)C(c2cccc([N+](=O)[O-])c2)C1C(=O)OC
Yield: 71 %

Procedure:
Upon boiling a solution of 7.6 g of 3-nitrobenzaldehyde and 14.5 g of 3-amino-3-ethoxyacrylic acid methyl ester in 40 ml of alcohol for 6 hours, 2-amino-4-(3-nitrophenyl)-6-ethoxy-4,5-dihydropyridine-3,5-dicarboxylic acid dimethyl ester of melting point 163° C (isopropanol) is obtained. Yield: 71% of theory.
Reaction SMILES: [C:1](OC([O-])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(C[NH:16][CH2:17][CH2:18][CH2:19][NH2:20])CN.O>C(Cl)Cl>[C:4]([O:3][C:1]([NH:20][CH:19]([CH2:19][CH2:18][CH2:17][NH2:16])[CH2:18][CH2:17][NH2:16])=[O:2])([CH3:7])([CH3:6])[CH3:5]
Reactant: CC(C)(C)OC(=O)OC(=O)[O-]
Reactant: NCCCNCCCN
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC(CCN)CCCN
Yield: 44.7 %

Procedure:
A solution of 33 g of tert-butyl dicarbonate in 200 ml of methylene chloride was added at 5° C. to a solution of 39.3 g of 3,3'-diaminodipropylamine in 300 ml of methylene chloride and after stirringf or 16 hours at 20° C., water was added, followed by decanting and evaporation to dryness. The residue was chromatographed on silica (eluant; methanol-ammonia (98-2)) to obtain 15.5 g of the expected product which was used as is for the next step.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][NH2:12].[CH3:13][S:14](Cl)(=[O:16])=[O:15]>N1C=CC=CC=1.ClCCl>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][NH:12][S:14]([CH3:13])(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: NCc1ccc([N+](=O)[O-])cc1F
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)NCc1ccc([N+](=O)[O-])cc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.3 %

Procedure:
To a stirred solution of (2-fluoro-4-nitrophenyl)methanamine (194 mg, 1.140 mmol) in pyridine, cooled to 0° C., were added methanesulfonyl chloride (248 mg, 2.166 mmol). The resulting reaction mixture was stirred for 1 h at room temperature. The mixture was dissolved in dichloromethane and washed with 1N HCl. The organic layer was dried over magnesium sulfate and filtered. The filtrate removed in vacuo. The crude was purified by column chromatography. N-(2-Fluoro-4-nitrobenzyl)methanesulfonamide (250 mg) was obtained as 88% yield.