Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Si:19]([CH3:22])([CH3:21])O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].CN(C)C=O.C(Cl)([Cl:30])=O>ClCCCl>[CH2:1]([Si:19]([CH3:22])([CH3:21])[Cl:30])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCC[Si](C)(C)O
Reactant: O=C(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: CCCCCCCCCCCCCCCCCC[Si](C)(C)Cl
Yield: 87 %

Procedure:
To the same reactor as used in Example 1 were added 82.2 g (0.25 mole) of octadecyldimethylsilanol, 330 g of 1,2-dichloroethane and 1.83 g (0.025 mole) of N,N-dimethylformamide, and 27.2 g (0.275 mole) of phosgene was introduced into the resulting mixture at a temperature of from 40° to 45° C. over 2 hours with stirring. After completion of the introduction, the same procedure as in Example 7 was carried out to obtain 75.5 g of octadecyldimethylchlorosilane.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=1)=[O:4].I[C:16]1C=CC(N)=C(C)C=1>>[F:14][C:2]([F:1])([F:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][C:7]=1[CH3:16])=[O:4]
Reactant: Cc1cc(I)ccc1N
Reactant: O=C(Nc1ccc(I)cc1)C(F)(F)F
Product: Cc1cc(I)ccc1NC(=O)C(F)(F)F

Procedure:
Title compound was synthesized in a manner analogous to Intermediate 32 using 4-iodo-2-methylaniline as a substrate. ES/MS calcd. for C9H7F3INO 328.95. Found m/z=330 (M+H)+.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]([OH:7])[CH:4]=[C:3]([CH2:8][CH:9]([NH2:13])[C:10]([OH:12])=[O:11])[CH:2]=1.Cl.[CH3:15]O>>[CH3:15][O:11][C:10](=[O:12])[CH:9]([NH2:13])[CH2:8][C:3]1[CH:2]=[CH:1][CH:6]=[C:5]([OH:7])[CH:4]=1
Reactant: CO
Reactant: NC(Cc1cccc(O)c1)C(=O)O
Agent: Cl
Product: COC(=O)C(N)Cc1cccc(O)c1

Procedure:
DL-m-Tyrosine (1 g) was stirred in a 3M solution of HCl in MeOH (10 ml) for 2 h at RT The solvent was removed and HV drying afforded 1.43 g of the desired compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:27][C:28](=O)[CH2:29][C:30](=[O:42])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH:41]=[N:40][N:39]=[CH:38]2)[CH:32]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH:21][C:28](=[O:27])[CH2:29][C:30](=[O:42])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH:38]=[N:39][N:40]=[CH:41]2)[CH:32]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2F)cc1N
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2cnnc2)c1
Product: CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2F)cc1NC(=O)CC(=O)c1cccc(-n2cnnc2)c1

Procedure:
Prepared from (3-amino-2′-fluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example G37) (302 mg, 1.0 mmol) and 3-oxo-3-(3-[1,2,4]triazol-4-yl-phenyl)-propionic acid tert.-butyl ester (Example H11) (345 mg, 1.2 mmol) according to the general procedure K. Obtained as a yellow amorphous substance (207 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(CN)CC1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCC(CNS(=O)(=O)c2ccc(Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
A solution of 0.844 g (4 mmol) of 4-chlorobenzenesulphonyl chloride in 5 ml of dichloromethane is added dropwise to a solution of 0.857 g (4 mmol) of tert-butyl 4-(aminomethyl)piperidine-1-carboxylate, 0.99 ml (6 mmol) of diisopropylethylamine and 0.024 g (0.2 mmol) of 4-dimethylaminopyridine in 9 ml of dichloromethane. The mixture is stirred at ambient temperature overnight. The organic phase is washed with 10 ml of water and then 4 ml of a 1N aqueous hydrochloric acid solution, 2 times 14 ml of water, 2 times 14 ml of a 1N aqueous sodium hydroxide solution, 3 times 14 ml of water and 14 ml of a saturated aqueous sodium chloride solution. It is dried over sodium sulphate and evaporated to dryness in order to obtain 1.371 g (3.52 mmol) of product in the form of an orange paste used as is in the following stage.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].N[C@H:7]([C:9]([OH:11])=[O:10])[CH3:8]>>[NH2:1][C@H:2]([C:3]([OH:5])=[O:4])[CH2:8][CH2:7][C:9](=[O:10])[OH:11]
Reactant: C[C@H](N)C(=O)O
Reactant: NCC(=O)O
Product: N[C@@H](CCC(=O)O)C(=O)O

Procedure:
Gly 471.4; Ala 576.9;
Reaction SMILES: [C:1]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)([CH3:4])([CH3:3])[CH3:2].C=O.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19](S(O)(=O)=O)=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[C:1]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][C:6]=1[CH2:7][C:6]1[CH2:26][C:16]2[C:21]([C:5]=1[C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: CC(C)(C)C1C=Cc2ccccc21
Agent: C=O
Solvent: Cc1ccccc1
Product: CC(C)(C)C1=C(CC2=C(C(C)(C)C)c3ccccc3C2)Cc2ccccc21
Temperature: 80 °C
Reaction time: 6 h
Yield: 216.4 %

Procedure:
In a 500 mL flask equipped with magnetic stirring bar were introduced 12.35 g (0.072 moles) of 1-t-butyl-indene, 1.43 g (0.048 moles) of para-formaldehyde and 2.73 g (0.014 moles) of para-toluenesulphonic acid in 200 ml of toluene; the mixture was heated to 80° C. and was maintained under stirring for 6 hours at 80° C. Then the reaction was quenched with water/NaHCO3; the conversion, measured by gas chromatographic analysis, was 79.5%. The organic layer was separated, washed with water and brought to dryness under reduced pressure. The crude product crystallized upon standing at room temperature, and then was further purified by washing with MeOH, thus isolating 10.8 g bis(3-t-butyl-2-indenyl)methane (purity of 90.9 by G.C.; yield=76.81%).
Reaction SMILES: [F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([C:13]([CH3:43])([CH3:42])[C:14]([N:16]([CH3:41])[C:17]2[C:18]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[CH3:40])=[CH:19][C:20]([N:23]3[CH2:27][C@H:26](O)[CH2:25][C@H:24]3[CH2:29][O:30][C:31](=[O:33])[CH3:32])=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(S(F)(F)[F:52])CC)C>ClCCl.[OH-].[Na+]>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C:13]([CH3:43])([CH3:42])[C:14]([N:16]([CH3:41])[C:17]2[C:18]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[CH3:40])=[CH:19][C:20]([N:23]3[CH2:27][C@@H:26]([F:52])[CH2:25][C@H:24]3[CH2:29][O:30][C:31](=[O:33])[CH3:32])=[N:21][CH:22]=2)=[O:15])[CH:4]=[C:3]([C:2]([F:1])([F:44])[F:45])[CH:8]=1
Reactant: CC(=O)OC[C@@H]1C[C@@H](O)CN1c1cc(-c2ccccc2C)c(N(C)C(=O)C(C)(C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cn1
Reactant: CCN(CC)S(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(=O)OC[C@@H]1C[C@H](F)CN1c1cc(-c2ccccc2C)c(N(C)C(=O)C(C)(C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cn1
Yield: 36.7 %

Procedure:
To a solution of 0.14 g (0.21 mmol) (2S,4R)-acetic acid 1-(5-{[2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl]-methyl-amino}-4-o-tolyl-pyridin-2-yl)-4-hydroxy-pyrrolidin-2-ylmethyl ester in 2 ml dichloromethane were added dropwise at 0° C. 0.03 ml (0.2 mmol) (diethylamino)sulfur trifluoride. After 1 h the reaction mixture was diluted with a 0.5 M aqueous sodium hydroxide solution and extracted with four portions of dichloromethane. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 47 mg (35%) of the title compound as a white solid.
Reaction SMILES: C([O:4][C@@H:5]1[C@@:31]2([CH3:32])[C:9](=[CH:10][CH2:11][C@@H:12]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:26])[CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH2:8][C@@H:7]([O:34]C(=O)C)[CH2:6]1)(=O)C.CCOCC.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)(=O)C>[OH:4][C@@H:5]1[C@@:31]2([CH3:32])[C:9](=[CH:10][CH2:11][C@@H:12]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:26])[CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH2:8][C@@H:7]([OH:34])[CH2:6]1
Reactant: CC(=O)O[C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@H]([C@H](C)COC5CCCCO5)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: C[C@H](COC1CCCCO1)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C

Procedure:
To a solution of 1.5 g. of (20S)-1α,3β-diacetoxy-20-methyl-21-tetrahydropyranyloxypregna-5-ene in 25 ml. of absolute ether was added 0.3 g. of lithium aluminum hydride and the suspension was stirred at room temperature for 1 hour. After cooling to 0°, 2 ml. of ethyl acetate was added and the mixture poured onto ice-water. The insoluble part was extracted with ethyl acetate, the organic solution was washed with water and dried over sodium sulfate. By filtration and evaporation under vacuum 1.4 g. of crystalline (20S)-1α,3β-dihydroxy-20-methyl-21-tetrahydropyranyloxypregna-5-ene was obtained. Recrystallization from methanol gave white crystals, m.p. 138°-141°; [α]D =-48.8° (c=0.5, chloroform).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:39])[CH2:16][NH:17][C:18]([C:20]2[CH:24]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([O:31]CC4C=CC=CC=4)[CH:26]=3)[NH:22][N:21]=2)=[O:19])[CH2:11][CH2:10]1.B(Br)(Br)Br>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:39])[CH2:16][NH:17][C:18]([C:20]2[CH:24]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=3)[NH:22][N:21]=2)=[O:19])[CH2:11][CH2:10]1
Reactant: O=C(NCC(=O)N1CCC(Nc2ccccc2Cl)CC1)c1cc(-c2cccc(OCc3ccccc3)c2)[nH]n1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: O=C(NCC(=O)N1CCC(Nc2ccccc2Cl)CC1)c1cc(-c2cccc(O)c2)[nH]n1
Temperature: -70 °C
Reaction time: 1 h
Yield: 44.7 %

Procedure:
A solution of 5-(3-benzyloxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide (0.19 g, 0.00035 mole) in dichloromethane was cooled to −70° C. 1 mL of a 1.6M solution of BBr3 in dichloromethane was then added dropwise with vigorous stirring. The reaction mixture was slowly brought to ambient temperature and stirring was continued at the same temperature for 1 hour. The reaction mixture was then cooled to −70° C. and ice cold water was added dropwise with stirring and while the mixture was slowly brought to ambient temperature. The product was extracted with dichloromethane and the organic layers were dried over sodium sulfate. The organic layer was collected and concentrated under reduced pressure. The resulting residue was recrystallized from ethyl acetate to afford 0.071 g (45%) of 5-(3-hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 454.16 (M+1)+, 94.25%, 1H NMR (DMSO-d6): δ 13.6 (s, 1H), 9.6 (s, 1H), 8.1 (s, 1H), 7.0 (m, 5H), 6.84 (d, 1H), 6.76 (d, 1H), 6.6 (m, 1H), 4.8 (s, 1H), 4.3 (d, 1H), 4.1 (d, 2H), 3.8 (d, 1H), 3.7 (s, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 1.95 (m, 2H), 1.3 (m, 2H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[Cl:10][C:11]1[CH:20]=[C:19]2[C:14]([C:15]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([S:28]([N:31]4[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]4)(=[O:30])=[O:29])=[CH:24][CH:23]=3)=[CH:16][CH:17]=[N:18]2)=[CH:13][CH:12]=1>>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[N:7]=[C:2]([N:34]2[CH2:35][CH2:36][N:31]([S:28]([C:25]3[CH:26]=[CH:27][C:22]([NH:21][C:15]4[C:14]5[C:19](=[CH:20][C:11]([Cl:10])=[CH:12][CH:13]=5)[N:18]=[CH:17][CH:16]=4)=[CH:23][CH:24]=3)(=[O:29])=[O:30])[CH2:32][CH2:33]2)[N:3]=1
Reactant: Cc1cc(C)nc(Cl)n1
Reactant: O=S(=O)(c1ccc(Nc2ccnc3cc(Cl)ccc23)cc1)N1CCNCC1
Product: Cc1cc(C)nc(N2CCN(S(=O)(=O)c3ccc(Nc4ccnc5cc(Cl)ccc45)cc3)CC2)n1

Procedure:
In the manner given in Example 9, part E, 2-chloro-4,6-dimethylpyrimidine is heated with [[4-[(7-chloro-4-quinolinyl)amino]phenyl]sulfonyl]piperazine to give 1-[(4,6-dimethyl-2-pyrimidinyl)]-4-[[4-[[7-chloro-4-quinolinyl]amino]phenyl]sulfonyl]piperazine.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]([CH2:8][CH2:9][CH3:10])[C:6]2[CH:11]=[CH:12][C:13]([CH2:15][O:16][Si:17]([CH3:23])([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:5]=2[N:4]=1.[CH2:24]([NH2:27])[CH2:25][CH3:26]>C(#N)C>[CH2:24]([NH:27][CH2:2][C:3]1[N:7]([CH2:8][CH2:9][CH3:10])[C:6]2[CH:11]=[CH:12][C:13]([CH2:15][O:16][Si:17]([CH3:23])([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:5]=2[N:4]=1)[CH2:25][CH3:26]
Reactant: CCCN
Reactant: CCCn1c(CCl)nc2cc(CO[Si](C)(C)C(C)(C)C)ccc21
Solvent: CC#N
Product: CCCNCc1nc2cc(CO[Si](C)(C)C(C)(C)C)ccc2n1CCC
Yield: 99 %

Procedure:
A solution of 2.0 g (5.6 mmole) of 1-{[2-(chloromethyl)-1-propylbenzimidazol-5-yl]methoxy}-1,1,2,2-tetramethyl-1-silapropane in 20 mL of anhydrous acetonitrile is treated with 10 mL of propylamine for 16 hr at room temperature. The solvent is removed in vacuo and the residue is partitioned between 30 mL of ethyl acetate and 10 mL of 1 N NaOH. The ethyl acetate layer is dried over anhydrous Na2SO4 and solvent removed in vacuo to afford 2.1 g (99%) of propyl({1-propyl-5-[(1,1,2,2-tetramethyl-1-silapropoxy)methyl]benzimidazol-2-yl}methyl)amine.
Reaction SMILES: C([O:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([CH3:18])=[CH:16][C:15]([C:19]2[N:28]=[C:27](Cl)[C:26]3[C:21](=[CH:22][C:23]([O:32][CH3:33])=[CH:24][C:25]=3[O:30][CH3:31])[N:20]=2)=[CH:14][C:13]=1[CH3:34])C1C=CC=CC=1.CO.C([O-])=O.[NH4+]>C1COCC1.[Pd]>[CH3:31][O:30][C:25]1[CH:24]=[C:23]([O:32][CH3:33])[CH:22]=[C:21]2[C:26]=1[CH:27]=[N:28][C:19]([C:15]1[CH:16]=[C:17]([CH3:18])[C:12]([O:11][CH2:10][CH2:9][OH:8])=[C:13]([CH3:34])[CH:14]=1)=[N:20]2
Reactant: COc1cc(OC)c2c(Cl)nc(-c3cc(C)c(OCCOCc4ccccc4)c(C)c3)nc2c1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc(OC)c2cnc(-c3cc(C)c(OCCO)c(C)c3)nc2c1
Temperature: 80 °C
Reaction time: 5 h
Yield: 25.4 %

Procedure:
To a 100 mL round bottom flask was added 2-amino-4,6-dimethoxy-benzamide (318 mg, 1.6 mmol), 4-(2-benzyloxy-ethoxy)-3,5-dimethyl-benzaldehyde (461 mg, 1.6 mmol), p-toluenesulfonic acid monohydrate (32 mg, 0.16 mmol), sodium hydrogensulfite (318 mg, 1.8 mmol) and dimethylacetamide (5 mL). The mixture was stirred in a 150° C. oil bath under nitrogen overnight. Water (40 mL) and ether (30 mL) were added. The precipitate was filtered off, washed with water then ether, and air-dried. The intermediate 2-[4-(2-benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one was obtained as light brown/beige solid. Yield 474 mg (64%). 2-[4-(2-Benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (474 mg, 1.03 mmol) was stirred in phosphorus oxychloride (10 mL) at 100° C. for 4 h. Excess phosphorus oxychloride was removed under reduced pressure. Ice was added and the solid was collected. The solid was washed with water and ether, and air-dried. 2-[4-(2-benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-4-chloro-5,7-dimethoxy-quinazoline was obtained as a light brown solid (yield: 356 mg, 72%). 2-[4-(2-Benzyloxy-ethoxy)-3,5-dimethyl-phenyl]-4-chloro-5,7-dimethoxy-quinazoline (192 mg, 0.4 mmol) was dissolved in a small amount of THF and 10% Pd/C (dry) (66 mg) was added. Anhydrous methanol (20 mL) and ammonium formate (955 mg) were added. The mixture was stirred in a 80° C. oil bath for 5 h. The mixture was filtered through Celite, washed with MeOH/DCM, purified by column chromatography to give 2-(4-(5,7-dimethoxyquinazolin-2-yl)-2,6-dimethylphenoxy)ethanol (36 mg, 25%) as an off-white solid. Selected data: MS (ES) m/z: 355.04; mp 169-170° C.
Reaction SMILES: O[C:2]1[CH:17]=[C:16]([OH:18])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[OH:13])=O.C([O-])(=O)C.[Na+].[F:24][C:25]([F:30])([F:29])[CH2:26][NH:27][NH2:28]>>[OH:18][C:16]1[CH:17]=[C:2]2[C:3]([C:4]([C:6]3[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=3[OH:13])=[N:28][N:27]2[CH2:26][C:25]([F:30])([F:29])[F:24])=[CH:14][CH:15]=1
Reactant: O=C(c1ccc(O)cc1O)c1ccc(O)cc1O
Reactant: NNCC(F)(F)F
Agent: CC(=O)[O-]
Agent: [Na+]
Product: Oc1ccc(-c2nn(CC(F)(F)F)c3cc(O)ccc23)c(O)c1
Yield: 17.3 %

Procedure:
Prepared according to Method B from 2,2′,4,4′-tetrahydroxybenzophenone (0.123 g, 0.5 mmol), sodium acetate (0.164 g, 2 mmol) and 2,2,2-trifluoroethylhydrazine (0.088 mL, 1.0 mmol) to give 0.028 g of product as a yellow solid
Reaction SMILES: N1N[N:3]=[N:4][C:5]=1[C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[Br:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16](Cl)=[O:17]>CC1C=CC=CC=1C>[Br:12][C:13]1[CH:14]=[C:15]([C:16]2[O:17][C:5]([C:6]3[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=3)=[N:4][N:3]=2)[CH:19]=[CH:20][CH:21]=1
Reactant: O=C(Cl)c1cccc(Br)c1
Reactant: c1cncc(-c2nn[nH]n2)c1
Solvent: Cc1ccccc1C
Product: Brc1cccc(-c2nnc(-c3cccnc3)o2)c1

Procedure:
16.8 g (114 mmol) of 3-(2H-tetrazol-5-yl)pyridine) according to Synthesis Example 7 and 25 g (114 mmol) of 3-bromobenzoylchloride were dissolved in 180 mL of o-xylene. The solution was reacted at 150° C. for 8 hours. The acquired reactant was purified under reduced pressure and washed with methanol, obtaining 30 g (Y=87%) of a white solid.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]([OH:16])[CH2:4][O:5][C:6]1[C:14]2[NH:13][C:12](=[O:15])[NH:11][C:10]=2[CH:9]=[CH:8][CH:7]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([NH:27][S:28]([C:31]2[CH:36]=[CH:35][C:34]([N:37]3[CH2:42][CH2:41][C:40](=O)[CH2:39][CH2:38]3)=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]>>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([NH:27][S:28]([C:31]2[CH:36]=[CH:35][C:34]([N:37]3[CH2:42][CH2:41][CH:40]([NH:1][CH2:2][C@H:3]([OH:16])[CH2:4][O:5][C:6]4[C:14]5[NH:13][C:12](=[O:15])[NH:11][C:10]=5[CH:9]=[CH:8][CH:7]=4)[CH2:39][CH2:38]3)=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]
Reactant: COc1ccc(NS(=O)(=O)c2ccc(N3CCC(=O)CC3)cc2)cc1OC
Reactant: NC[C@H](O)COc1cccc2[nH]c(=O)[nH]c12
Product: COc1ccc(NS(=O)(=O)c2ccc(N3CCC(NC[C@H](O)COc4cccc5[nH]c(=O)[nH]c45)CC3)cc2)cc1OC

Procedure:
The title compound was prepared from 4-((2S)-3-Amino-2-hydroxy-propoxy)-1,3-dihydrobenzoimidazol-2-one and Reference Example 73, N-(3,4-dimethoxy-phenyl)-4-(4-oxo-piperidin-1-yl)-benzenesulfonamide, according to the procedure of Example 1 as a grey solid. 1H NMR (DMSO) δ 1.28 (m, 2H), 1.84 (m, 2H), 2.65(m, 1H), 2.81 (m, 4H), 3.62(s, 3h), 3.64(s, 3H). 3.77(m, 2H), 3.89(m, 2H), 4.03(m, 1H), 4.87(bs, 1H), 6.59 (m, 4H), 6.74(d, 1H, J=8.7 Hz), 6.83(d, 1H, J=8.1 Hz), 6.91 (d, 2H, J=9.0 Hz), 7.45(d, 2H, J=9.0 Hz), 10.57 (bs, 1H), 10.69 (bs, 1H); MS (ES) m/z: 598.1 (MH+); HRMS for C29H35N5O7S: 598.2296 (MH+).
Reaction SMILES: [O:1]1[C:5]2([CH2:9][CH2:8][O:7][CH2:6]2)[CH2:4][C:3]([C:10]2[CH:11]=[CH:12][C:13]([O:17][CH3:18])=[C:14]([OH:16])[CH:15]=2)=[N:2]1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[CH2:27](Br)[CH3:28]>CN(C)C=O.O>[CH2:27]([O:16][C:14]1[CH:15]=[C:10]([C:3]2[CH2:4][C:5]3([CH2:9][CH2:8][O:7][CH2:6]3)[O:1][N:2]=2)[CH:11]=[CH:12][C:13]=1[O:17][CH3:18])[CH3:28]
Reactant: COc1ccc(C2=NOC3(CCOC3)C2)cc1O
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOc1cc(C2=NOC3(CCOC3)C2)ccc1OC
Temperature: 25 °C
Yield: 90 %

Procedure:
To a solution of the compound No. 73 (1 eq) in dimethylformamide (10 mL), was added potassium iodide (0.1 eq) and potassium carbonate (2 eq). The reaction mixture was stirred at room temperature and ethyl bromide (2 eq) was added. The reaction mixture was stirred for overnight at room temperature. The reaction mixture was cooled and diluted with water, extracted with ethylacetate and washed with saturated solution of sodium chloride. The organic solvent was removed under reduced pressure. The residue thus obtained was purified by column chromatography to furnish the title compound. Yield=90%.
Reaction SMILES: Br.[CH3:2][N:3]1[C:12]2[C:7](=[CH:8][C:9]([CH3:13])=[CH:10][CH:11]=2)[C:6](=[O:14])[N:5]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[C:4]1=[O:21].[CH2:22]([O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][C:39]=1[O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[N:36]=[CH:35][N:34]=[C:33]2Cl)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[CH2:22]([O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][C:39]=1[O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[N:36]=[CH:35][N:34]=[C:33]2[N:18]1[CH2:19][CH2:20][CH:15]([N:5]2[C:6](=[O:14])[C:7]3[C:12](=[CH:11][CH:10]=[C:9]([CH3:13])[CH:8]=3)[N:3]([CH3:2])[C:4]2=[O:21])[CH2:16][CH2:17]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: Cc1ccc2c(c1)c(=O)n(C1CCNCC1)c(=O)n2C
Reactant: Clc1ncnc2cc(OCc3ccccc3)c(OCc3ccccc3)cc12
Agent: Br
Product: Cc1ccc2c(c1)c(=O)n(C1CCN(c3ncnc4cc(OCc5ccccc5)c(OCc5ccccc5)cc34)CC1)c(=O)n2C
Yield: 54 %

Procedure:
The procedure similar to that described in Example 61 was repeated, except that 836.0 mg (2.36 mmol) of 1,2,3,4-tetrahydro-1,6-dimethyl-2,4-dioxo-3-(4-piperidinyl)quinazoline hydrobromide (Compound v) obtained in Example 41 was used and 6,7-dibenzyloxy-4-chloroquinazoline was used in place of 4-chloro-6,7-dimethoxyquinazoline. As a result, 786.3 mg (yield: 54%) of Compound 88 was obtained as white crystals.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:25]=[CH:26][C:27]([C:29]([NH:31][CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])=[O:30])=[CH:28][C:12]=3[N:11]=2)=[CH:6][CH:5]=1)(=[NH:3])[NH2:2].[CH2:38]([P:40](C#N)([CH2:42][CH3:43])=[O:41])[CH3:39]>CN(C)C=O>[CH2:38]([P:40]([NH:3][C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:25]=[CH:26][C:27]([C:29]([NH:31][CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])=[O:30])=[CH:28][C:12]=3[N:11]=2)=[CH:8][CH:9]=1)=[NH:2])([CH2:42][CH3:43])=[O:41])[CH3:39]
Reactant: CCP(=O)(C#N)CC
Reactant: COC(=O)CCNC(=O)c1ccc2c(c1)nc(-c1ccc(C(=N)N)cc1)n2CCCCc1ccccc1
Solvent: CN(C)C=O
Product: CCP(=O)(CC)NC(=N)c1ccc(-c2nc3cc(C(=O)NCCC(=O)OC)ccc3n2CCCCc2ccccc2)cc1

Procedure:
Prepared by reacting 2-(4-amidino-phenyl)-5-[(2-methoxycarbonyl-ethyl)-aminocarbonyl]-1-(4-phenyl-butyl)-benzimidazole with diethylphosphorylcyanide in dimethylformamide.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.[F:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][NH:16][C:17]([C:19]2[S:23][C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C:25]3=[O:29])=[N:21][C:20]=2[CH3:30])=[O:18])=[CH:13][CH:12]=1>>[F:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][NH:16][C:17]([C:19]2[S:23][C:22]([N:24]3[CH2:28][CH2:27][CH:26]([CH2:2][C:3]4[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=4)[C:25]3=[O:29])=[N:21][C:20]=2[CH3:30])=[O:18])=[CH:13][CH:12]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: Cc1nc(N2CCCC2=O)sc1C(=O)NCc1ccc(F)cc1
Product: Cc1nc(N2CCC(Cc3ccc(F)cc3)C2=O)sc1C(=O)NCc1ccc(F)cc1
Yield: 36 %

Procedure:
Following the procedure as described in Example 2, making variation as required to use 1-(bromomethyl)-4-fluorobenzene in place of 1-(bromomethyl)-4-(trifluoromethyl)benzene to react with N-(4-fluorobenzyl)-4-methyl-2-(2-oxopyrrolidin-1-yl)thiazole-5-carboxamide, the title compound was obtained as a white solid in 36% yield: mp 196-197° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.31-7.26 (m, 2H), 7.13 (dd, J=8.6, 5.6 Hz, 2H), 7.06-6.90 (m, 4H), 6.03 (t, J=5.6 Hz, 1H), 4.52 (d, J=5.6 Hz, 2H), 4.06-3.95 (m, 1H), 3.95-3.70 (m, 1H), 3.29-3.10 (m, 1H), 3.05-2.92 (m, 1H), 2.88-2.70 (m, 1H), 2.60 (s, 3H), 2.32-2.17 (m, 1H), 2.00-1.80 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 174.8, 176.3, 162.3, 161.8, 155.4, 152.9, 133.8, 133.7, 130.4, 129.6, 118.5, 115.7, 115.5, 45.9, 44.4, 43.4, 35.6, 24.2, 17.3; MS (ES+) m/z 442.2 (M+1).