Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[NH:13][C:12](=[O:14])[C:11]2[C:6](=[CH:7][C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:9][CH:10]=2)[N:5]=1.[CH3:19]I>CN(C=O)C>[CH3:3][C:4]1[N:13]([CH3:19])[C:12](=[O:14])[C:11]2[C:6](=[CH:7][C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:9][CH:10]=2)[N:5]=1
Reactant: COC(=O)c1ccc2c(=O)[nH]c(C)nc2c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc2c(=O)n(C)c(C)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 47.1 %

Procedure:
To a stirred suspension of sodium hydride (60% in mineral oil, 51 mg, 1.28 mmol) in DMF (5 mL) under an atmosphere of nitrogen was added methyl 2-methyl-4-oxo-3,4-dihydroquinazoline-7-carboxylate (0.14 g, 0.64 mmol) in DMF (2 mL) dropwise. Methyl iodide (80 μL, 1.28 mmol) was then added to the mixture and the resulting solution was stirred at rt overnight. The reaction was quenched with water and extracted with DCM (2×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated to afford methyl 2,3-dimethyl-4-oxo-3,4-dihydroquinazoline-7-carboxylate (70 mg, 50%). LC-MS: (FA) ES+ 233.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.[CH3:19][O:20][C:21]1[C:22](=[O:45])[C:23]([CH3:44])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][C:41](=[O:43])[CH3:42])=[C:35]([CH:39]=2)[C:36](O)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]>C(Cl)Cl>[CH3:19][O:20][C:21]1[C:22](=[O:45])[C:23]([CH3:44])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][C:41](=[O:43])[CH3:42])=[C:35]([CH:39]=2)[C:36]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]
Reactant: C1CCNCC1
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)O)c2)=C(C)C1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)N3CCCCC3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 16.9 %

Procedure:
Piperidine (0.027 g, 0.321 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.062 g, 0.321 mmol) were added to a methylene chloride solution (5 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.040 g, 0.107 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1) to obtain the titled compound (0.008 g, 0.0181 mmol, 17%).
Reaction SMILES: C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:10]([CH2:21][N:22]([CH:39]([CH3:41])[CH3:40])[C:23](=[O:38])[C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH2:33][CH2:34][CH2:35][O:36][CH3:37])[CH:25]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:39]([N:22]([CH2:21][C@H:10]1[C@H:11]([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][NH:8][CH2:9]1)[C:23](=[O:38])[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH2:33][CH2:34][CH2:35][O:36][CH3:37])[CH:25]=1)([CH3:41])[CH3:40]
Reactant: COCCCOc1cc(C(=O)N(C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@H]2CNc2ccccc2)C(C)C)ccc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCCOc1cc(C(=O)N(C[C@@H]2CNC[C@H]2CNc2ccccc2)C(C)C)ccc1OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-phenylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (65 mg, 0.12 mmol) in 2 mL CH2Cl2, TFA (139 μL, 1.8 mmol) is added. The mixture is stirred 2 h at RT, and poured into a saturated solution of NaHCO3. The layers are separated, and the aqueous one is back-extracted twice with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is purified by flash chromatography on an Isolute SPE Flash NH2 column (eluent: CH2Cl2/MeOH 100:0 to 97:3) to give the title product. TLC, Rf (SiO2—NH2, CH2Cl2/MeOH 95:5)=0.6. MS (LC-MS): 470.0 [M+H]+; tR (HPLC, Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 3.37 min.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].Cl[CH2:21][C:22](=[O:24])[CH3:23]>C1COCC1.O>[CH2:1]([N:8]([CH2:21][C:22](=[O:24])[CH3:23])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)CNCc1ccccc1
Reactant: CC(=O)CCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CN(CC(C)=O)Cc1ccccc1
Temperature: 50 °C
Reaction time: 48 h

Procedure:
A solution of ethyl 2-(benzylamino)acetate (40 g, 207 mmol) and NaHCO3 (20.9 g, 248 mmol) in THF (400 mL) and water (30 mL) was heated to 50° C. 1-chloropropan-2-one (23.9 g, 259 mmol) was added and the reaction was stirred at 50° C. for 2 d. Water was added the solution extracted with hexanes. The organic layer was separated, dried, filtered, and concentrated to afford crude ethyl 2-(benzyl(2-oxopropyl)amino)acetate (118) which without further purification
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-])=O)[C:3]=1[NH:11][CH2:12][CH2:13][OH:14].[CH:15](O)=O>[Pd]>[F:1][C:2]1[C:3]2[N:11]([CH2:12][CH2:13][OH:14])[CH:15]=[N:8][C:4]=2[CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1cccc(F)c1NCCO
Reactant: O=CO
Agent: [Pd]
Product: OCCn1cnc2cccc(F)c21
Reaction time: 8 h
Yield: 64 %

Procedure:
2-[(2-fluoro-6-nitrophenyl)amino]ethanol (18.3 g, 91.5 mmol) dissolved in 90 mL of formic acid is added to a suspension of Pd—C 10% (300 mg) in 10 ml of formic acid. The mixture is shaken in a Parr apparatus under atmospheric pressure of H2 overnight. The reaction mixture is filtered over Celite, the solvent is evaporated under vacuum and the resulting residue dissolved in NH3 2M in ethanol. This solution is stirred at room temperature for 1 h (to cleave the formic acid adduct). A precipitate forms. This mixture is evaporated to dryness and purified by column chromatography (SiO2, DCM/MeOH 10:1 to 5:1), giving the desired product as a white solid (10.5 g, 64%) TLC: DCM/MeOH 5:1, Rf=0.23.
Reaction SMILES: [CH:1]([C:4]1[S:5][C:6]([C:9]([O:11]CC)=[O:10])=[CH:7][N:8]=1)([CH3:3])[CH3:2].[OH-].[Li+]>CO.O>[CH:1]([C:4]1[S:5][C:6]([C:9]([OH:11])=[O:10])=[CH:7][N:8]=1)([CH3:3])[CH3:2]
Reactant: CCOC(=O)c1cnc(C(C)C)s1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)c1ncc(C(=O)O)s1

Procedure:
A solution of ethyl 2-isopropylthiazole-5-carboxylate (example 55, step a) (0.33 g) in methanol (6 mL) was treated with a solution of lithium hydroxide (0.079 g) in water (3 mL) and the resultant mixture stirred for 2 hours at 20° C. The methanol was evaporated off under reduced pressure and the residue partitioned between ether and brine. The aqueous layer was acidified by dropwise addition of dilute hydrochloric acid and the mixture extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 0.185 g.
Reaction SMILES: [CH2:1]([NH:13][CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(=O)([O-])[O-].[K+].[K+].[CH3:27][S:28](Cl)(=[O:30])=[O:29]>ClCCl>[CH2:1]([N:13]([CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[S:28]([CH3:27])(=[O:30])=[O:29])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CS(=O)(=O)Cl
Reactant: CCCCCCCCCCCCNCc1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CCCCCCCCCCCCN(Cc1cccnc1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A 4.1 g. portion of 3-dodecylaminomethylpyridine was dissolved in 15 ml. of dichloromethane, and 2.7 g. of potassium carbonate and 1.6 ml. of methanesulfonyl chloride were added. The mixture was stirred for 3 days at ambient temperature, and was then diluted with dichloromethane and extracted with water. The organic layer was dried and evaporated to an oil, which was dissolved in dichloromethane and chromatographed over silica gel, eluting with dichloromethane. The product-containing fractions were combined and evaporated to obtain 3.5 g. of oil which crystallized on standing, and was triturated with cold petroleum ether and diethyl ether. The solids were dried to obtain 3.2 g. of the desired product, m.p. 43°-44°.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1([OH:12])[CH2:11][CH2:10][CH2:9]1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH:26]=[C:25]([S:30]([O-:32])=[O:31])[CH:24]=[CH:23]3)=[CH:16][CH:15]=1.[Na+]>>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH:26]=[C:25]([S:30]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[C:8]2([OH:12])[CH2:11][CH2:10][CH2:9]2)(=[O:32])=[O:31])[CH:24]=[CH:23]3)=[CH:16][CH:15]=1
Reactant: O=S([O-])c1ccc2cc(-c3ccc(F)cc3)ccc2c1
Reactant: OC1(c2ccncc2Br)CCC1
Agent: [Na+]
Product: O=S(=O)(c1ccc2cc(-c3ccc(F)cc3)ccc2c1)c1cnccc1C1(O)CCC1

Procedure:
Prepared according to the method of Example 6 Step 4 using 1-(3-bromopyridin-4-yl)cyclobutanol and sodium 6-(4-fluorophenyl)naphthalene-2-sulfinate. 1H NMR (500 MHz, CDCl3): δ 8.91 (1H, s), 8.77 (1H, d, J=4.9 Hz), 8.54 (1H, s), 8.08-8.02 (3H, m), 7.88-7.82 (2H, m), 7.69 (2H, dd, J=5.2, 8.7 Hz), 7.42 (1H, d, J=5.1 Hz), 7.21 (2H, t, J=8.6 Hz), 4.74 (1H, s), 2.59-2.45 (4H, m), 2.35-2.27 (1H, m), 1.76-1.68 (1H, m). m/z (ES+) 434 [MH+].
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]4[N:27]=[CH:26][C:25]([CH2:28][CH2:29][CH3:30])=[CH:24][N:23]=4)[CH2:18][CH2:17]3)=[CH:11][C:10]2=[O:31])=[CH:5][CH:4]=1.ClC1C=C(C=CC=1)C(OO)=[O:37]>C(Cl)Cl>[CH3:1][S:2]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:17][CH2:18][N:19]([C:22]4[N:23]=[CH:24][C:25]([CH2:28][CH2:29][CH3:30])=[CH:26][N:27]=4)[CH2:20][CH2:21]3)=[CH:11][C:10]2=[O:31])=[CH:7][CH:8]=1)=[O:37]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCc1cnc(N2CCC(Oc3ccn(-c4ccc(SC)cc4)c(=O)c3)CC2)nc1
Solvent: ClCCl
Product: CCCc1cnc(N2CCC(Oc3ccn(-c4ccc(S(C)=O)cc4)c(=O)c3)CC2)nc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 93.6 %

Procedure:
To a stirring solution of 1-(4-(methylthio)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one (51.4 mg, 0.118 mmol) in CH2Cl2 (15 mL) at 0° C. was added a solution of 3-Chloroperoxybenzoic acid (26.4 mg, 0.118 mmol) in 5 mL CH2Cl2. The reaction was stirred at 0° C. for 15 min and then quenched with Na2SO3 (sat. solution in H2O). The organic layer was washed with H2O, brine, dried over Na2SO4 and concentrated in vacuo to a white solid. The solid was purified by flash chromatography (SiO2, 0 to 10% MeOH in CH2Cl2) to yield 50 mg of desired product as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.16 (s, 2H), 7.77 (d, J=8.31 Hz, 2H), 7.57 (d, J=8.31 Hz, 2H), 7.23 (d, J=7.34 Hz, 1H), 5.94-6.11 (m, 2 H), 4.44-4.64 (m, 1H), 4.07-4.31 (m, 2H), 3.50-3.74 (m, 2H), 2.77 (s, 3H), 2.40 (t, J=7.58 Hz, 2H), 1.98-2.17 (m, 2H), 1.73-1.93 (m, 2H), 1.50-1.64 (m, 2H), 0.93 (t, =7.34 Hz, 3H). MS (ESI) 453 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.Cl[CH2:21]Cl.[OH-].[Na+].S(OC)(OC)(=O)=O>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:21])[C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1
Reactant: ClCCl
Reactant: O=C1CN=C(c2ccccc2)c2cc(Cl)ccc2N1
Agent: [Na+]
Agent: [OH-]
Solvent: COS(=O)(=O)OC
Solvent: O
Product: CN1C(=O)CN=C(c2ccccc2)c2cc(Cl)ccc21
Temperature: 0 °C

Procedure:
Dissolve 5.4 g. (0.02 moles) of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (e.g. product of Example 3) in 35 ml. of dichloromethane and add to this solution 1.2 g. of NaOH (1.5 moles) dissolved in 17 ml. of water. Cool the mixture with good agitation to 0° C. and add slowly 3.8 g. (0.03 moles) of dimethyl sulfate with good cooling and stirring. After all the dimethyl sulfate is added remove the cooling bath and continue stirring for an additional 2 hours. Add water and methylene chloride to the reaction mixture. Separate the layers and wash the methylene chloride layers with water. Dry the organic solution over anhydrous sodium sulfate and evaporate. After recrystallization, 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one is obtained which after drying under vacuum at 110° C. shows a melting point of 129.5°-130.5° (corr.) and no depression on mixed melt with an authentic sample.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:9]([C:11]3[CH2:12][CH2:13][N:14]([C:17]([O-:19])=[O:18])[CH2:15][CH:16]=3)=[CH:10][C:3]=12.[CH2:29]([N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[C:33]([C:45]2[CH:50]=[CH:49][C:48]([N+:51]([O-:53])=[O:52])=[CH:47][CH:46]=2)=[N:32]1)[CH3:30]>>[CH2:29]([N:31]1[CH:35]=[C:34]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[N:8]([S:20]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)(=[O:22])=[O:21])[C:9]([C:11]4[CH2:12][CH2:13][N:14]([C:17]([O:19][C:3]([CH3:10])([CH3:4])[CH3:2])=[O:18])[CH2:15][CH:16]=4)=[CH:10][C:3]=23)[C:33]([C:45]2[CH:46]=[CH:47][C:48]([N+:51]([O-:53])=[O:52])=[CH:49][CH:50]=2)=[N:32]1)[CH3:30]
Reactant: O=C([O-])N1CC=C(c2cc3c(Br)ccnc3n2S(=O)(=O)c2ccccc2)CC1
Reactant: CCn1cc(B2OC(C)(C)C(C)(C)O2)c(-c2ccc([N+](=O)[O-])cc2)n1
Product: CCn1cc(-c2ccnc3c2cc(C2=CCN(C(=O)OC(C)(C)C)CC2)n3S(=O)(=O)c2ccccc2)c(-c2ccc([N+](=O)[O-])cc2)n1

Procedure:
Following the procedure described for Intermediate 11 with 4-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3,6-dihydro-1(2H)-pyridinecarboxylate and 1-ethyl-3-(4-nitrophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole gave the title compound. ESMS [M+H]+: 655.4
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:6][C:7]([NH:9][C:10]1[NH:11][C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH2:25][CH2:26][CH2:27]Cl)=[CH:13][C:14]=1[C:15]([NH2:17])=[O:16])=[O:8]>>[NH2:6][C:7]([NH:9][C:10]1[NH:11][C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH2:25][CH2:26][CH2:27][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:13][C:14]=1[C:15]([NH2:17])=[O:16])=[O:8]
Reactant: C1CCNC1
Reactant: NC(=O)Nc1[nH]c(-c2ccccc2OCCCCl)cc1C(N)=O
Product: NC(=O)Nc1[nH]c(-c2ccccc2OCCCN2CCCC2)cc1C(N)=O
Temperature: 120 °C
Reaction time: 5 h
Yield: 42 %

Procedure:
Pyrrolidine (0.5 mL) was added to 2-aminocarbonylamino-5-[2-(3-chloropropyloxy)phenyl]pyrrole-3-carboxamide (Compound No. 4-29, 30 mg, 0.090 mmol), the whole was sealed and stirred at 120° C. for 5 hours. This mixture was purified by silica gel column chromatography to give the target compound (14 mg) as a brown amorphous Powder (Yield 42%).
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[OH:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18](=[O:32])[N:19]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])[CH:20]=[N:21]2)=[CH:16][C:15]=1[O:33][CH3:34].O[CH2:36][CH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:34][O:33][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:14]=1[O:13][CH2:36][CH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1)[N:21]=[CH:20][N:19]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:28])([CH3:29])[CH3:30])[C:18]2=[O:32]
Reactant: COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O
Reactant: OCCN1CCCC1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCN1CCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.5 %

Procedure:
Diethyl azodicarboxylate (566 mg, 3.25 mmol) was added dropwise to a solution of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (765 mg, 2.5 mmol), (prepared as described for the starting material in Example 22), 1-(2-hydroxyethyl)pyrrolidine (374 mg, 3.25 mmol) and triphenylphosphine (851 mg, 3.25 mmol) in methylene chloride (15 ml). The mixture was stirred for 1 hour at ambient temperature and further triphenylphosphine (861 mg, 3.25 mmol) followed by diethyl azodicarboxylate (566 mg, 3.25 mmol) was added. The mixture was stirred for 1 hour at ambient temperature and the solvent was removed by evaporation. The residue was dissolved in ethyl acetate/ether and extracted with 2M hydrochloric acid. The aqueous layer was basified by addition of solid sodium hydrogen carbonate and extracted with methylene chloride. The combined extracts were dried (MgSO4), and the solvent removed by evaporation. The resulting oil was purified by column chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (90/10 followed by 80/20) to give 6-methoxy-3-((pivaloyloxy)methyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (550 mg, 55%).
Reaction SMILES: BrCCBr.[Mg].[CH2:6]1[O:14][CH:9]([CH:10]([CH3:13])[CH2:11]Br)[O:8][CH2:7]1.CON(C)[C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH3:26])[CH:20]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:6]1[O:14][CH:9]([CH:10]([CH3:13])[CH2:11][C:18](=[O:27])[C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH3:26])[CH:20]=2)[O:8][CH2:7]1
Reactant: CC(CBr)C1OCCO1
Reactant: CON(C)C(=O)c1ccc(C)c(C)c1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: BrCCBr
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)CC(C)C2OCCO2)cc1C
Reaction time: 1 h
Yield: 38.5 %

Procedure:
0.29 ml (3.4 mmol) of 1,2-dibromoethane was added to a suspension of 1.66 g (68.1 mmol) of magnesium in 5 ml of anhydrous tetrahydrofuran under a stream of nitrogen. 9.96 g (51.1 mmol) of 3-bromo-2-methylpropionaldehyde ethylene acetal [prepared as described in step (i) above] were then added dropwise to the resulting mixture, whilst ice-cooling, after which the mixture was stirred for 1 hour. A solution of 6.58 g (34.1 mmol) of N-methoxy-N-methyl-3,4-dimethylbenzamide in 30 ml of tetrahydrofuran was then added dropwise to the mixture, and the resulting mixture was stirred, whilst ice-cooling for 1 hour. A saturated aqueous solution of ammonium chloride was then added to the mixture, and the resulting mixture was extracted twice with ethyl acetate. The organic extracts were combined and washed with a saturated aqueous solution of sodium chloride, after which they were dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The residue thus obtained was applied to a silica gel chromatography column and eluted with a 6:1 by volume mixture of hexane and ethyl acetate, to give 3.26 g (yield 39%) of the title compound as a colorless oily substance.
Reaction SMILES: O[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[NH:8][C:9](=O)[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:21]>N1C=CC=CC=1.CC1C=CC(C)=CC=1>[N+:16]([C:12]1[CH:11]=[C:10]([C:9]2[S:21][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][C:3]=3[N:8]=2)[CH:15]=[CH:14][CH:13]=1)([O-:18])=[O:17]
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: O=C(Nc1cnccc1O)c1cccc([N+](=O)[O-])c1
Solvent: Cc1ccc(C)cc1
Solvent: c1ccncc1
Product: O=[N+]([O-])c1cccc(-c2nc3cnccc3s2)c1
Temperature: 140 °C
Reaction time: 18 h
Yield: 80.7 %

Procedure:
A mixture of N-(4-hydroxypyridin-3-yl)-3-nitrobenzamide (1.33 g, 5.2 mmol) and P2S5 (2.40 g, 10.4 mmol) in pyridine (6.0 mL) and p-xylene (24 mL) was stirred at 140° C. for 18 h. The solvent was removed under vacuo while hot and the residue was purified by recrystallization from EtOH to afford 2-(3-nitrophenyl)thiazolo[4,5-c]pyridine as a yellow solid (1.08 g, yield: 81%). MS (ESI) calcd. for C12H7N3O2S (m/z): 257, found: 258 [M+1]+.
Reaction SMILES: [CH3:1][S@:2](=[O:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[N:3][C:4](=[O:17])[C:5]1[CH:10]=[C:9]([C:11]#[C:12][Si](C)(C)C)[CH:8]=[N:7][CH:6]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29](I)=[CH:28][N:27]=1>>[NH2:25][C:26]1[N:27]=[CH:28][C:29]([C:12]#[C:11][C:9]2[CH:8]=[N:7][CH:6]=[C:5]([CH:10]=2)[C:4]([N:3]=[S@@:2]([CH3:1])(=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:17])=[CH:30][CH:31]=1
Reactant: C[Si](C)(C)C#Cc1cncc(C(=O)N=[S@@](C)(=O)c2ccccc2)c1
Reactant: Nc1ccc(I)cn1
Product: C[S@@](=O)(=NC(=O)c1cncc(C#Cc2ccc(N)nc2)c1)c1ccccc1
Yield: 84.4 %

Procedure:
In a manner similar to that described in Example 443, (S)—N-[methyl(oxo)phenyl-λ6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamide (100 mg, 0.28 mmol) and 2-amino-5-iodopyridine (69.3 mg, 0.31 mmol) were reacted to give the title compound as light yellow solid (89 mg).
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[C:8]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)=[CH:9][C:10](=O)[NH:11][CH:12]=2)[CH:2]=1.O=P(Cl)(Cl)[Cl:23]>>[Cl:23][C:10]1[CH:9]=[C:8]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)[C:7]([C:3]2[CH:4]=[CH:5][CH:6]=[C:1]([CH3:20])[CH:2]=2)=[CH:12][N:11]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cccc(-c2c[nH]c(=O)cc2-c2ccncc2)c1
Product: Cc1cccc(-c2cnc(Cl)cc2-c2ccncc2)c1

Procedure:
5-m-tolyl-1H-[4,4′]bipyridinyl-2-one (262 mg, 1.0 mmole) in POCl3 (5 mL) was heated to 105° C. for 12 hr. POCl3 was removed under reduced pressure. The residue was diluted with methylene chloride and was carefully quenched with aqueous sodium carbonate. Standard work up, followed by purification (silica gel, hexane/ethyl acetate) gave the title compound. MS (m/z): Calcd. C17H13N2Cl (M+): 280.5, found (M+H)+: 281.0 and 283.1.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8](I)[C:7]([NH2:11])=[N:6][CH:5]=1.O=[C:14]([CH3:18])[C:15]([OH:17])=[O:16].CCN(CC)CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]2[CH:18]=[C:14]([C:15]([OH:17])=[O:16])[NH:11][C:7]2=[N:6][CH:5]=1)=[O:12]
Reactant: COC(=O)c1cnc(N)c(I)c1
Reactant: CC(=O)C(=O)O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1cnc2[nH]c(C(=O)O)cc2c1
Reaction time: 1 h

Procedure:
A solution of 5.6 g 6-Amino-5-iodo-nicotinic acid methyl ester, 5.3 g 2-Oxo-propionic acid, 11.1 g NEt3, 4.2 g Triphenylphosphine and 1.1 g Pd(OAc)2 in 100 mL DMF was heated under argon to 100° C. After 10 h the reaction mixture was concentrated under reduced pressure and the residue was strirred with 250 mL water for 1 h. The precipitated product was collected by filtration and washed with water. The crude product was subjected to the next reaction step without further purification.
Reaction SMILES: O[CH:2]=[C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([O:14][CH3:15])[CH:10]=2)[N:5]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:4]1[CH3:23].[CH:24]([NH2:27])([CH3:26])[CH3:25]>C1C=CC=CC=1>[CH:24]([NH:27][CH:2]=[C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([O:14][CH3:15])[CH:10]=2)[N:5]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:4]1[CH3:23])([CH3:26])[CH3:25]
Reactant: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CO)C1C
Reactant: CC(C)N
Solvent: c1ccccc1
Product: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CNC(C)C)C1C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of 3.2 g. of 3-hydroxymethylene-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid, ethyl ester in 30 ml. of benzene containing 650 mg. of isopropylamine is allowed to stir at room temperature for 48 hrs. The reaction solution is concentrated to give 4 g. of a yellow foam which could not be induced to crystallize.