Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].[CH2:5]([O:17]S(C1C=CC=CC=1)(=O)=O)[CH2:6]CCCCCCCCCC.[Na].[OH2:28]>>[C:3]([O:17][CH2:5][CH3:6])(=[O:28])[CH:2]=[CH2:1].[C:5]([OH:17])(=[O:28])[C:3]([CH3:2])=[CH2:4]
Reactant: CCCCCCCCCCCCOS(=O)(=O)c1ccccc1
Reactant: C=CC=C
Reactant: O
Agent: [Na]
Product: C=C(C)C(=O)O
Product: C=CC(=O)OCC
Temperature: 70 °C
Yield: 0.15 %

Procedure:
Into an agitated reactor is charged 1303 g of a 1000 A butadiene rubber latex (35.3% solids) with a pH of 8.1. The mixture is heated to 70° C. and 184 g of an aqueous AgAg stream is added over a 40 minute period. The AgAg stream contains 1.85% agglomerating agent A, 0.54% sodium dodecylbenzene sulfonate, and the balance water. Then 0.75% shell and core agglomerating agent is added resulting in (0.15% ethyl acrylate/methacrylic acid copolymer) in the agglomerated latex. 55% Of the small 1000 A particles are converted to larger size. To this 70° C. agglomerated latex is added over a five hour period, 565 g of a monomer stream, and 550 g of an aqueous stream. The monomer stream contains 71.7% styrene, 27.9% acrylonitrile, and 0.34% n-octyl mercaptan. The aqueous stream contains 2.58% sodium dodecylbenzene sulfonate, 0.23% sodium persulfate, and the balance water. The latex is heated for 0.5 hours after the additions are finished, steam stripped, stabilized with antioxidants, and the polymer isolated by freeze coagulation. The grafted rubber concentrate is blended with SAN on a 0.8 inch Welding Engineers twin screw extruder to give an ABS resin having 22% rubber and an excellent balance of physical properties of gloss, flow and toughness. Injection molded properties of the ABS are: Ty--5770 psi; Tr--4530 psi; % E--11; Izod--5.8 ft.lbs/inch of notch; gloss--94%; MFR--3.0 g/10 minutes (Cond. I).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.C([Li])(C)(C)C.CN(C)[CH:24]=[O:25].[Cl-].[NH4+]>O1CCCC1>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:5]2[N:6]=[CH:7][C:2]([CH:24]=[O:25])=[CH:3][CH:4]=2)=[CH:11][CH:12]=1
Reactant: CN(C)C=O
Reactant: Clc1ccc(CNc2ccc(Br)cn2)cc1
Agent: [Cl-]
Agent: [Li]C(C)(C)C
Agent: [NH4+]
Solvent: C1CCOC1
Product: O=Cc1ccc(NCc2ccc(Cl)cc2)nc1
Temperature: -78 °C
Reaction time: 1.5 h

Procedure:
(5-Bromo-pyridin-2-yl)-(4-chloro-benzyl)-amine (11, 3.81 g, 13 mmol) was dissolved in 150 mL of tetrahydrofuran at −78° C. under an atmosphere of nitrogen and tert-butyllithium (7.6 mL, 1.7 M in hexane) was added dropwise. After 30 minutes additional tert-butyllithium (16 mL, 1.7 M in hexane) was added dropwise and the reaction was stirred for 1.5 hours at −78° C. N,N-Dimethylformamide (2.4 mL, 31 mmol) was added and the mixture was stirred for 1.5 hours at −78° C., then allowed to warm up to room temperature for 1 hour. The reaction was poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic portion was dried over anhydrous sodium sulfate and concentrated. The desired compound was crystallized from a mixture of ether in ethyl acetate. The remaining material was purified with silica gel chromatography eluting with ethyl acetate and hexane to provide additional compound (12, 2.7 g, 85%).
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH2:13][C:12]3([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:11]2=[O:20])=[CH:6][CH:5]=1.O=C(Cl)[O:25][C:26](Cl)(Cl)Cl.[CH3:31][NH:32][CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1>>[CH3:31][N:32]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1)[C:26]([N:17]1[CH2:16][CH2:15][C:12]2([C:11](=[O:20])[N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:21])[F:22])=[CH:5][CH:6]=3)[CH2:14][CH2:13]2)[CH2:19][CH2:18]1)=[O:25]
Reactant: O=C1N(c2ccc(OC(F)(F)F)cc2)CCC12CCNCC2
Reactant: CNCCc1ccccn1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Product: CN(CCc1ccccn1)C(=O)N1CCC2(CC1)CCN(c1ccc(OC(F)(F)F)cc1)C2=O

Procedure:
This material was prepared in analogy to example 251 step B) from 2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one, diphosgene and methyl-(2-pyridin-2-yl-ethyl)-amine. MS (ESI): 477.4 (MH+).
Reaction SMILES: [NH3:1].F[C:3]1[N:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[N:4]=1>C(OCC)C>[NH2:1][C:3]1[N:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[N:4]=1
Reactant: N
Reactant: Fc1cc(F)nc(F)n1
Solvent: CCOCC
Product: Nc1nc(F)cc(F)n1
Temperature: 25 °C

Procedure:
69.7 g (4.1 mol) of liquid ammonia were added at -30° to -20° C. to a stirred mixture of 250 g (1.865 mol) of 2,4,6-trifluoropyrimidine and 3.3 1 of diethyl ether within 1 hour. To work up, the reaction mixture was warmed to 25° C. and the precipitate was filtered off. Washing with ether, stirring in water, renewed filtration and drying resulted in 203 g (83% of theory) of the desired product (melting point 214°-216° C.). It was possible by concentrating the ether filtrate to about 1/3 of its volume to isolate a further 20 g (8% of theory) of this compound, of melting point 193°-196° C., from a 1:1 mixture with the isomeric 4-amino compound. Comparative experiment (according to SU-A 547,447--1975)
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[C@H:39]([CH3:40])[CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:41])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:42]2[CH:43]=[C:44]([CH:51]=[CH:52][CH:53]=2)[CH2:45][O:46]S(C)(=O)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:54][N:55]1[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1.C1C[O:64]CC1>>[CH:45]([OH:46])=[O:64].[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[C@H:39]([CH3:40])[CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:41])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:42]2[CH:43]=[CH:44][CH:45]=[C:52]([CH2:51][N:58]3[CH2:59][CH2:60][N:55]([CH3:54])[CH2:56][CH2:57]3)[CH:53]=2)[N:6]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: C[C@@H]1CCC[C@H](C)N1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(COS(C)(=O)=O)c4)c4ccccc43)cn12
Reactant: C1CCOC1
Reactant: CN1CCNCC1
Product: C[C@@H]1CCC[C@H](C)N1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(CN5CCN(C)CC5)c4)c4ccccc43)cn12
Product: O=CO
Temperature: 50 °C
Reaction time: 24 h
Yield: 19 %

Procedure:
To a solution of Intermediate 130b (0.25 mmol) in THF (2.5 mL) was added N-methylpiperazine (277 μL, 2.50 mmol) and the reaction stirred at 50° C. for 24 h. After cooling, the mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by FCC on silica, using a gradient of 0-10% [2M NH3 in MeOH] in DCM, followed by MDAP (Method 7) purification, to give the title compound (37 mg, 19%). LCMS (Method 5): Rt 3.77 min, m/z 745 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.55 (3H, d, J=6.2 Hz), 0.58 (3H, d, J=6.2 Hz), 1.23 (9H, s), 1.35-1.54 (3H, m), 1.63-1.68 (2H, m), 1.72-1.86 (2H, m), 1.86-1.92 (1H, m), 2.01-2.06 (2H, m), 2.07 (3H, s), 2.26 (4H, br s), 2.34 (4H, br s), 3.08-3.20 (2H, m), 3.46 (2H, s), 4.78 (1H, td, J=8.6, 5.9 Hz), 5.47 (1H, t, J=4.2 Hz), 6.28 (1H, s), 7.00 (1H, d, J=8.6 Hz), 7.15 (1H, dd, J=9.8, 2.1 Hz), 7.18-7.25 (2H, m), 7.25-7.31 (3H, m), 7.32-7.37 (2H, m), 7.41 (1H, t, J=7.6 Hz), 7.61 (1H, d, J=9.7 Hz), 7.83 (1H, d, J=1.8 Hz), 8.05 (1H, s), 8.12 (1.1H, s).
Reaction SMILES: [CH2:1]([N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:7]=[N:6]1)[CH2:2][C:3]#[CH:4].Br[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][F:25])[N:19]=1>>[F:25][CH2:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([C:4]#[C:3][CH2:2][CH2:1][N:5]2[CH:9]=[C:8]([C:10]3[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=3)[N:7]=[N:6]2)[N:19]=1
Reactant: C#CCCn1cc(-c2ccc(F)cc2)nn1
Reactant: FCc1cccc(Br)n1
Product: FCc1cccc(C#CCCn2cc(-c3ccc(F)cc3)nn2)n1
Yield: 21.3 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 1-(but-3-ynyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole (100 mg, 0.47 mmol) and 2-bromo-6-(fluoromethyl)pyridine (97 mg, 0.51 mmol, Example 190(E)). Reaction time: 2 hours. The crude residue was purified by flash chromatography (DCM/MeOH 98.5:1.5) to yield 32 mg (0.10 mmol, 21%) of 2-(fluoromethyl)-6-(4-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)but-1-ynyl)pyridine as a yellow solid (M.P.=100-103° C.).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[H-].[Na+].Cl[C:15]1[CH:20]=[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][Si](C(C)(C)C)(C)C)=[CH:24][CH:23]=2)[C:18]([N+:36]([O-:38])=[O:37])=[CH:17][N:16]=1.O>CN(C=O)C>[OH:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:19]2[C:18]([N+:36]([O-:38])=[O:37])=[CH:17][N:16]=[C:15]([O:11][C:7]3[CH:6]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:10]=[CH:9][CH:8]=3)[CH:20]=2)=[CH:23][CH:24]=1
Reactant: CC(=O)Nc1cccc(O)c1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(Nc2cc(Cl)ncc2[N+](=O)[O-])cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)Nc1cccc(Oc2cc(Nc3ccc(O)cc3)c([N+](=O)[O-])cn2)c1
Temperature: 60 °C
Yield: 33.6 %

Procedure:
A solution of 3-acetamidophenol (10.8 g, 72 mmol) in DMF (50 mL) was added dropwise to a slurry of NaH (60% in oil, 2.88 g, 72 mmol) over 1 h. A solution of the product from Step 1 (13.7 g, 36.0 mmol) in DMF (50 mL) was added and the resulting mixture was heated to 60° C. overnight. The reaction mixture was poured into water and extracted with EtOAc. The organic layers were combined, washed with brine, dried (MgSO4), filtered and the filtrate was concentrated to give an oil which was purified by chromatography (10-100% EtOAc in hexanes) to give the title compound (4.6 g, 34%) as an orange solid. MS (ES+) m/e 381 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12](=[O:15])[NH:13][CH:14]=2)=[CH:5][CH:4]=1.[Cl:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([F:27])([F:26])[F:25])=[N:22][CH:23]=1>>[ClH:16].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12](=[O:15])[N:13]([CH2:17][C:18]3[CH:23]=[N:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][CH:19]=3)[CH:14]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(-c2ccc(=O)[nH]c2)cc1
Reactant: FC(F)(F)c1ccc(CCl)cn1
Product: COc1ccc(-c2ccc(=O)n(Cc3ccc(C(F)(F)F)nc3)c2)cc1
Product: Cl
Yield: 16.6 %

Procedure:
According to Scheme 5 Step 2: The title compound was prepared from 5-(4-methoxyphenyl)-(1H)-pyridin-2-one (1 eq, 0.50 mmol, 0.10 g, Example 7 Step 1) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (1.5 eq, 0.74 mmol, 0.15 g) according to the procedure described for Example 1 Step 2. Reaction conditions: 6 hours at 70° C. and 48 hours at room temperature. The crude product was purified by silica gel chromatography (AIT Flashsmart prepacked column 10 g SiO2, CH2Cl2/AcOEt 90/10). The purified oil was dissolved in Et2O and HCl (4M in dioxane) was added. The resulting precipitate was filtered, dried to afford 5-(4-methoxyphenyl)-1-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2(1H)-one hydrochloride (83 μmol, 30 mg, 17%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([OH:15])=O)[CH:3]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:38][CH2:39][C:40]1[S:44][CH:43]=[N:42][CH:41]=1.C(N(C(C)C)CC)(C)C>CN(C)C(=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([NH:38][CH2:39][C:40]2[S:44][CH:43]=[N:42][CH:41]=2)=[O:15])[CH:3]=1
Reactant: CCOc1nc(C(=O)O)cc(N)c1C#N
Reactant: NCc1cncs1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)N(C)C
Product: CCOc1nc(C(=O)NCc2cncs2)cc(N)c1C#N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 20 mL vial a solution of Example 104A (32.5 mg, 0.16 mmol) dissolved in N,N-dimethylacetamide (0.8 mL) was added, followed by the addition of O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (50.4 mg, 0.16 mmol) dissolved in N,N-dimethylacetamide (0.8 mL). Then, 5-(aminomethyl)thiazole (21.7 mg, 0.19 mmol) dissolved in N,N-dimethylacetamide (0.6 mL) was added followed by the addition of diisopropyl ethyl amine (57.9 uL, 0.31 mmol) dissolved in N,N-dimethylacetamide (0.8 mL). The mixture was shaken at room temperature overnight. The reaction was checked by LC/MS and concentrated to dryness. The residue was dissolved in 1:1 dimethyl sulfoxide/methanol and purified by reverse phase HPLC (0-70% CH3CN in 10 mM aq. ammonium acetate) to give the titled compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.25-1.39 (m, 3H) 4.43-4.54 (m, 2H) 4.58-4.68 (m, 2H) 7.04-7.14 (m, 1H) 7.37-7.45 (m, 1H) 8.83-9.19 (m, 1H); MS (ESI) positive ion 304 (M+H).
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([CH:8]2[CH2:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:19])[CH:14]=3)[O:9]2)[CH:5]=[CH:6][CH:7]=1.OC1C=CC(O)=CC=1C(=O)C.[Cl:31]C1C=C(C=CC=1)C=O>>[Cl:31][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:19])[CH:14]=3)[O:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1cccc(Cl)c1
Reactant: O=C1CC(c2cccc(F)c2)Oc2ccc(O)cc21
Agent: CC(=O)c1cc(O)ccc1O
Product: O=C1CC(c2cccc(Cl)c2)Oc2ccc(O)cc21

Procedure:
2-(3-Chlorophenyl)-6-hydroxychroman-4-one was prepared as described for 2-(3-fluorophenyl)-6-hydroxychroman-4-one in Example 9(a) starting from 2.0 g of 2′,5′-dihydroxyacetophenone and 1.85 g of 3-chlorobenzaldehyde. The product was recrystallised from acetic acid. 1H NMR (400 MHz, d6-DMSO) δ: 9.47 (s, 1H), 7.62 (s, 1H), 7.51-7.45 (m, 3H), 7.12 (d, 1H, J 3.0 Hz), 7.05 (dd, 1H, J 8.8, 3.0 Hz), 6.98 (d, 1H, J 8.8 Hz), 5.58 (dd, 1H, J 13.1, 2.9 Hz), 3.18 (dd, 1H, J −16.9, 13.1 Hz), 2.81 (dd, 1H, J −16.9, 2.9 Hz).
Reaction SMILES: [OH:1][CH:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:3][SiH2]C1C=CC=CN=1.[F-].[K+].C(=O)([O-])[OH:20].[K+].OO>CO.O.O1CCCC1>[C:11]1([CH:2]([OH:1])[CH2:3][OH:20])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: OC(C[SiH2]c1ccccn1)c1ccccc1
Reactant: O=C([O-])O
Agent: OO
Agent: [F-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: OCC(O)c1ccccc1
Temperature: 50 °C
Reaction time: 6 h
Yield: 95.5 %

Procedure:
To 129 mg (0.5 mmol) of the (2-hydroxy-2-phenylethyl)(2-pyridyl)silane obtained in Example 6, a solution of 58 mg (1.0 mmol) of potassium fluoride and 100 mg(1.0 mmol) of potassium hydrogencarbonate in methanol(1 ml)/tetrahydrofuran(1 ml) was added, followed by 1.71 g (15 mmol) of 30% aqueous hydrogen peroxide. The mixture was continued to be stirred at an inner temperature of 50° C. for 6 hours, and then cooled to room temperature. After addition of 10 ml of water, the mixture was extracted with four portions of 10 ml of diethyl ether. The separated organic layers were combined together and washed with 10 ml of a 15% aqueous sodium thiosulfate solution. After drying over magnesium sulfate, the residue after the evaporation of the solvent was purified with silica gel chromatograph to give 66 mg of phenyl-1,2-ethanediol. Yield: 96%.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([Br:9])[CH:6]=[CH:5][C:4]=1[OH:10])[CH3:2].C1(=O)O[CH2:14][CH2:13][O:12]1.C(=O)([O-])[O-].[K+].[K+].O>CN1C(=O)CCC1>[Br:9][C:7]1[CH:6]=[CH:5][C:4]([O:10][CH2:14][CH2:13][OH:12])=[C:3]([CH2:1][CH3:2])[CH:8]=1
Reactant: CCc1cc(Br)ccc1O
Reactant: O=C1OCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: CCc1cc(Br)ccc1OCCO
Temperature: 125 °C
Yield: 82.1 %

Procedure:
To a solution of 2-ethyl-4-bromophenol (3.5 g, 17.4 mmol) and ethylene carbonate (3.22 g, 37 mmol) in NMP (60 mL) was added potassium carbonate (5.17 g, 37.4 mmol). The resulting mixture was heated to 125° C. and maintained for 3 h. The reaction was cooled and poured into water (250 mL) and extracted with EtOAc (2×100 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (10–20% EtOAc in hexanes) to give the product (3.5 g, 82% yield) as a clear oil. 1H NMR (300 MHz, CDCl3) δ: 1.19 (t, J=7.6 Hz, 3 H), 1.89 (brs, 1 H), 2.61 (q, J=7.6 Hz, 2 H), 4.05 (m, 4 H), 6.70 (d, J=8.7 Hz, 1 H), 7.24 (m, 2 H).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25]>>[ClH:1].[CH3:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25]
Reactant: Cc1ccc(N)cc1[N+](=O)[O-]
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Product: COc1cc2ncnc(Nc3ccc(C)c([N+](=O)[O-])c3)c2cc1OC
Product: Cl

Procedure:
Using analogous procedures to those described in the portion of Example 2 which is concerned with the preparation of starting materials, 4-chloro-6,7-dimethoxyquinazoline was reacted with 4-methyl-3-nitroaniline to give 4-(4-methyl-3-nitroanilino)-6,7-dimethoxyquinazoline hydrochloride; NMR: 2.54 (s, 3H), 3.98 (s, 3H), 4.02 (s, 3H), 7.38 (s, 1H), 7.58 (m, 1H), 8.06 (m, 1H), 8.43 (m, 2H), 8.89 (s, 1H), 11.72 (s, 1H); Mass: M+H+ 341 and that material was reduced during 5 hours to give 4-(3-amino-4-methylanilino)-6,7-dimethoxyquinazoline; NMR: 2.04 (s, 3H), 3.9 (s, 3H), 3.92 (s, 3H), 4.88 (s, 2H), 6.8 (m, 1H), 6.9 (m, 1H), 7.03 (s, 1H), 7.12 (m, 1H), 7.8 (s, 1H), 8.38 (s, 1H); 9.2 (s, 1H); Mass: M+H+ 311.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](SC)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:22](O)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31].[CH3:32][CH:33]([NH2:35])[CH3:34].[CH3:36][N:37]([CH3:42])[CH2:38][CH2:39][NH:40][CH3:41]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([N:40]([CH2:39][CH2:38][N:37]([CH3:42])[CH3:36])[CH3:41])[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:22]([NH:35][CH:33]([CH3:34])[CH3:32])=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31]
Reactant: CNCCN(C)C
Reactant: CC(C)N
Reactant: CSc1nc(-c2cc(C(=O)O)ccc2C)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Product: Cc1ccc(C(=O)NC(C)C)cc1-c1nc(N(C)CCN(C)C)nc2c1ccc(=O)n2-c1c(F)cccc1F

Procedure:
The title compound was prepared from 3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzoic acid by following the procedures in Example 19 using 2-propanamine for the amide formation and N,N,N′-trimethyl-1,2-ethanediamine for the displacement reaction.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[C:11]([CH3:17])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C.[Pd]>[NH2:16][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:10][C:11]=1[CH3:17]
Reactant: Cc1nc(NC(=O)OC(C)(C)C)ccc1C#N
Agent: [Pd]
Solvent: CC(=O)O
Product: Cc1nc(NC(=O)OC(C)(C)C)ccc1CN
Reaction time: 88 h

Procedure:
A mixture of 2-t-butoxycarbonylamino-5-cyano-6-methylpyridine (14.68 g, 62.9 mmol) and 10% Pd/C (1.5 g) in glacial acetic acid (150 ml) was shaken on a Parr apparatus at 60 psi for 88 h. The reaction was filtered through celite and was evaporated in vacuo. The residue was dissolved in water and the solution was washed with methylene chloride (2 times), then was basified with sodium carbonate and extracted with ethyl acetate (2 times). The combined ethyl acetate layers were dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized (ethyl acetate/hexanes) to give the title compound:
Reaction SMILES: ClC(OCC(C)C)=O.[C:9]([O:13][C:14](=[O:40])[CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[N:20]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[C:21](=[O:32])[C:22]2[C:27]([CH:28]=1)=[CH:26][C:25]([C:29](O)=[O:30])=[CH:24][CH:23]=2)([CH3:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C.[BH4-].[Na+]>ClCCl.CO>[F:39][C:36]1[CH:37]=[CH:38][C:33]([N:20]2[C:19]([CH2:18][CH2:17][CH2:16][CH2:15][C:14]([O:13][C:9]([CH3:10])([CH3:12])[CH3:11])=[O:40])=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH2:29][OH:30])[CH:26]=3)[C:21]2=[O:32])=[CH:34][CH:35]=1
Reactant: CC(C)(C)OC(=O)CCCCc1cc2cc(C(=O)O)ccc2c(=O)n1-c1ccc(F)cc1
Agent: CC(C)COC(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CCCCc1cc2cc(CO)ccc2c(=O)n1-c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 84 %

Procedure:
Isobutyl chloroformate (0.285 mL, 2.184 mmol) was added to a stirred, 0° C. mixture of 3-(5-(tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid (800 mg, 1.820 mmol) and Hunig's Base (0.636 mL, 3.64 mmol) in Dichloromethane (20 mL) and the mixture was stirred at 0° C. for 3 h. The mixture was concentrated under reduced pressure with bath temp at 20° C., the residue was taken up in Dichloromethane (20 mL), NaBH4 (138 mg, 3.64 mmol) was added, the mixture was stirred at room temperature for 16 h. MeOH (10 mL) was added, and the resultant mixture was kept stirring at room temperature for 1 h. The mixture was diluted with dichloromethane (60 mL), washed with aqueous sodium hydrogen carbonate (saturated, 1×10 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane=1:1 to give tert-butyl 5-(2-(4-fluorophenyl)-6-(hydroxymethyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (650 mg, 1.528 mmol) as a white solid.
Reaction SMILES: [CH:1]([O:14][N:15]1[C:24](=[O:25])[CH:23]2[CH:17]([N:18]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH2:19][CH:20]=[CH:21][CH2:22]2)[C:16]1=[O:37])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]1([Mg]Br)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1COCC1.C(OCC)C>[CH:1]([O:14][NH:15][C:16]([CH:17]1[CH:23]([C:24](=[O:25])[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:22][CH:21]=[CH:20][CH2:19][N:18]1[S:26]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)(=[O:28])=[O:27])=[O:37])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Br[Mg]c1ccccc1
Reactant: COc1ccc(S(=O)(=O)N2CC=CCC3C(=O)N(OC(c4ccccc4)c4ccccc4)C(=O)C32)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1ccc(S(=O)(=O)N2CC=CCC(C(=O)c3ccccc3)C2C(=O)NOC(c2ccccc2)c2ccccc2)cc1
Temperature: -78 °C
Reaction time: 2.5 h

Procedure:
7-Benzhydryloxy-1-(4-methoxybenzenesulfonyl)-2,5,5a,8a-tetrahydro-1H-pyrrolo[3,4-b]azepine-6,8-dione (100 mg, 0.19 mmol) was dissolved in THF (2 mL) and cooled to -78° C. This solution was treated dropwise with a 3 M solution of phenyl magnesium bromide in diethyl ether and then warmed to ambient temperature. The reaction mixture was stirred another 2.5 hrs at room temperature, cooled to 0° C., and quenched with saturated aqueous NH4Cl (2 mL). This mixture was then diluted with H2O and diethyl ether and the layers were separated. The organic phase was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (silica, 5 to 10% ethyl acetate in toluene) to give 3-benzoyl-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid benzhydryloxy-amide; MS: (M+H)+ 596.9, (M+NH4)+ 614.2.