Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([N:13]3[CH2:20][CH:19]4[CH:15]([CH2:16][NH:17][CH2:18]4)[CH2:14]3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:21]1[N:22]([C:26]2[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=2[C:28](O)=[O:29])[N:23]=[CH:24][CH:25]=1>>[C:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([N:13]3[CH2:14][CH:15]4[CH:19]([CH2:18][N:17]([C:28]([C:27]5[CH:31]=[CH:32][CH:33]=[CH:34][C:26]=5[N:22]5[N:23]=[CH:24][CH:25]=[N:21]5)=[O:29])[CH2:16]4)[CH2:20]3)[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)c1ccccc1-n1nccn1
Reactant: c1ccc(-c2ccnc(N3CC4CNCC4C3)n2)cc1
Product: O=C(c1ccccc1-n1nccn1)N1CC2CN(c3nccc(-c4ccccc4)n3)CC2C1

Procedure:
The title compound was prepared in a manner analogous to Example 15 utilizing Intermediate 26 and Intermediate 2. MS (ESI): mass calculated for C25H23N7O, 437.50; m/z found 438.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.46-8.31 (m, 1H), 8.21-7.91 (m, 3H), 7.82-7.59 (m, 2H), 7.58-7.39 (m, 6H), 7.01-6.97 (m, 1H), 4.04-3.31 (m, 7H), 3.17-2.86 (m, 3H).
Reaction SMILES: [OH-].[Na+].[CH:3]1([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:5][CH2:4]1.[CH2:15]([CH:17]1[O:19][CH2:18]1)Cl>O.C(O)C>[CH:3]1([CH2:6][O:7][C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH:17]3[CH2:18][O:19]3)=[CH:12][CH:13]=2)[CH2:4][CH2:5]1
Reactant: ClCC1CO1
Reactant: Oc1ccc(OCC2CC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: c1cc(OCC2CO2)ccc1OCC1CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 0.46 g of sodium hydroxide in 1.8 ml water and 14 ml ethanol, 1.64 g of p-(cyclopropylmethoxy)-phenol and 5.54 g of epichlorohydrin is stirred at room temperature in a nitrogen atmosphere for 24 hours and left at room temperature for 21/2 days. The solvent is evaporated in vacuo and the residue is taken up in ether, washed with water and sodium chloride solution. After drying over anhydrous magnesium sulfate, the solution is filtered and concentrated under reduced pressure to yield p-(cyclopropylmethoxy)-phenoxymethyloxirane which is used directly in the condensation.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([NH2:19])=[O:18])[C:5]([CH3:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:20][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([NH2:19])=[O:18])=[N:7][C:2]([NH:21][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[N:3][CH:4]=1
Reactant: Cc1cnc(Cl)nc1CCc1ccccc1CC(N)=O
Reactant: Nc1cccnc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: O
Solvent: C1COCCO1
Product: Cc1cnc(Nc2cccnc2)nc1CCc1ccccc1CC(N)=O
Temperature: 150 °C
Yield: 10.2 %

Procedure:
A mixture of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamide (K6) (0.050 g, 0.17 mmol), 3-aminopyridine (0.019 g, 0.21 mmol), Pd(OAc)2 (0.8 mg, 0.003 mmol), Cs2CO3 (0.169 g, 0.518 mmol) and Xantphos (4 mg, 0.007 mmol) in 1,4-dioxane (1 mL) was heated under microwave irradiation at 150° C. for 10 minutes. Water (30 mL) was added and the resulting suspension was sonicated for 1 minute. The precipitate was collected by filtration then adsorbed onto silica gel and purified by silica gel column chromatography (CombiFlash Rf, 12 g SiO2 cartridge, 0-10% MeOH in DCM) to give the title compound 24 as a light pink solid (6 mg, 10%); 1H NMR (300 MHz, d4-MeOH) δ 8.87 (s, 1H), 8.26 (d, J=7.4 Hz, 1H), 8.16 (s, 1H), 8.10 (s, 1H), 7.34 (dd, J=8.1, 4.6 Hz, 1H), 7.23-7.27 (m, 1H), 7.16-7.20 (m, 3H), 3.65 (s, 2H), 3.12-3.17 (m, 2H), 2.97-3.02 (m, 2H), 2.12 (s, 3H). LCMS-B: rt 4.649 min; m/z 348 [M+H]+.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C:2]1=[O:7].[Br:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([CH2:15]Cl)[CH:14]=1>>[Br:8][C:9]1[CH:14]=[C:13]([CH2:15][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][C:2]2=[O:7])[CH:12]=[N:11][CH:10]=1
Reactant: O=C1CCCCN1
Reactant: ClCc1cncc(Br)c1
Product: O=C1CCCCN1Cc1cncc(Br)c1

Procedure:
In analogy to the procedure described for the preparation of intermediates B-1 [B], piperidin-2-one has been coupled to 3-bromo-5-chloromethyl-pyridine (intermediate B-1 [A]) to yield the title compound as a colorless oil. MS: 269.2, 271.2 (M+H+).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5].[C:8]1(=O)[CH2:12][CH2:11][CH2:10][CH2:9]1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+].[OH-].[Na+]>C(Cl)Cl>[CH:8]1([NH:1][CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5])[CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: O=C1CCCC1
Reactant: COC(=O)CCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Solvent: ClCCl
Product: COC(=O)CCNC1CCCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 74.2 %

Procedure:
Methyl 3-aminopropanoate (9.37 g, 0.09 mol) was dissolved in DCM (200 mL). Cyclopentanone (6.43 mL, 0.07 mol, 0.77 eq), sodium acetate (5.96 g, 0.07 mol, 0.77 eq) and sodium triacetoxyborohydride (22 g, 0.10 mol, 1.11 eq) were added then the reaction was stirred at rt for 16h. 20% Sodium bicarbonate (100 mL) and 2 M sodium hydroxide (50 mL) were added and the product extracted using DCM/H2O. The organic extracts were combined, washed with sat. NaCl, dried (MgSO4) and evaporated under reduced pressure to give the product as a pale yellow oil (8.90 g, 55%); MS+ve: 172.4.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([OH:10])[CH3:9].C([Li])CCC.CCCCCC.[CH2:22]([N:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O1CCCC1.CCOCC.O>[CH2:22]([N:29]1[CH2:34][CH2:33][C:32]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH:8]([OH:10])[CH3:9])([OH:35])[CH2:31][CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: CC(O)c1ccccc1Br
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(O)c1ccccc1C1(O)CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 49.2 %

Procedure:
To a stirred solution of (RS)-1-(2-bromo-phenyl)-ethanol (8.0 g, 39.8 mmol) −70° C. in tetrahydrofuran (40 ml) was added dropwise a 1.6M n-butyllithium solution in hexane (57.2 ml, 91.5 mmol) over a period of 20 min. After 2 hours, a solution of 1-benzyl-4-piperidone (10.2 ml, 55.7 mmol) in tetrahydrofuran (32 ml) was added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The mixture was poured into a stirred mixture of water (200 ml) and ether (200 ml). The aqueous layer was extracted with ether (2×100 ml). The combined extracts were washed with water (80 ml), dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was chromatographed on silica gel (eluent: heptane/ethylacetate 3:7) to yield 6.1 g (49%) of (RS)-1-benzyl-4-[2-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ol as a white solid. MS m/e: 312 (M+H+).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([NH:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH2:25][CH2:26][O:27][Si](C)(C)C(C)(C)C)[CH:20]=[CH:19]3)=[O:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(C1C=CC(/C=C/C(O)=O)=CC=1)(C)(C)C.C[Si](C)(OCCN1C2C(=CC(N)=CC=2)C=C1)C(C)(C)C>>[C:1]([C:5]1[CH:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([NH:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH2:25][CH2:26][OH:27])[CH:20]=[CH:19]3)=[O:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(/C=C/C(=O)Nc2ccc3c(ccn3CCO[Si](C)(C)C(C)(C)C)c2)cc1
Agent: CC(C)(C)[Si](C)(C)OCCn1ccc2cc(N)ccc21
Agent: CC(C)(C)c1ccc(/C=C/C(=O)O)cc1
Product: CC(C)(C)c1ccc(/C=C/C(=O)Nc2ccc3c(ccn3CCO)c2)cc1

Procedure:
(2E)-3-[4-(tert-Butyl)phenyl]-N-{1-[2-(1,1,2,2-tetramethyl-1-silapropoxy)ethyl]indol-5-yl}prop-2-enamide. According to the procedure used to prepare Example 1, 4-tert-butyl-trans-cinnamic acid (100 mg, 0.50 mmol, EMKA-Chemie) and 1-[2-(1,1,2,2-tetramethyl-1-silapropoxy)ethyl]indole-5-ylamine, Example 73(a), (145 mg, 0.50 mmol) provided the title product. MS (ESI, pos. ion) m/z: 477 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([OH:16])=O)[CH:13]=[C:8]2[C:7]([CH2:17][N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)=[CH:6]1.Cl.[CH3:31][O:32][NH2:33]>>[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([NH:33][O:32][CH3:31])=[O:16])[CH:13]=[C:8]2[C:7]([CH2:17][N:18]2[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]2)=[CH:6]1
Reactant: CON
Reactant: CN1CCN(Cc2cn(Cc3ccc(F)cc3F)c3cnc(C(=O)O)cc23)CC1
Agent: Cl
Product: CONC(=O)c1cc2c(CN3CCN(C)CC3)cn(Cc3ccc(F)cc3F)c2cn1

Procedure:
The title compound was prepared by coupling of 1-(2,4-difluorobenzyl)-3-[(4-methylpiperazin-1-yl)methyl]-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid and O-methylhydroxylamine hydrochloride in analogy to step 2 of example 17. 1H NMR (MeOH-d4) δ 8.77 (s, 1H), 8.43 (s, 1H), 7.59 (s, 1H), 7.27-7.03 (m, 1H) 7.01-6.93 (m, 2H), 5.55 (s, 2H), 3.82 (s, 5H), 2.82 (m, 4H), 2.66 (m, 4H), 2.50 (s, 3H). LCMS (APCI, M+H+): 430.2. Anal. (C22H22F2N5O3×1.5H2O×0.8AcOH)C, H, N.
Reaction SMILES: [Cl-].[Ca+2].[Cl-].[O:4]1[CH:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]1.S(=O)(=O)(O)O.C(=O)([O-])O.[Na+].[OH:27][CH2:28][CH:29]([CH2:31][OH:32])[OH:30]>O>[OH: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][O:27][CH2:28][CH:29]([CH2:31][OH:32])[OH:30]
Reactant: CCCCCCCCCCC1CO1
Reactant: OCC(O)CO
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Ca+2]
Solvent: O
Product: OCCCCCCCCCCCCOCC(O)CO
Temperature: 72.5 °C
Reaction time: 0.25 h
Yield: 96.7 %

Procedure:
Separately, a 100 ml mixing vessel equipped with a calcium chloride-containing tube was charged with 36.9 g (0.20 mole) of 1,2-epoxydodecane. While the charged 1,2-epoxydodecane was stirred and cooled with water, a concentrated sulfuric acid was gradually dropped in an amount of 0.4 g (0.004 mole) into the cooled 1,2-epoxydodecane. After stirring for 15 minutes, the resultant mixture was placed into the dropping apparatus attached to the reaction vessel and was dropped into glycerol contained in the reaction vessel and maintained at a temperature of 70 to 75° C. over a time of 2 hours. Then the reaction of the mixture was carried out at a temperature of 70 to 75° C. for one hour. After the exhaustion of the starting material, namely 1,2-epoxydodecane, was confirmed by a thin-layer chromatography, the reaction was stopped. A powdered sodium hydrogen carbonate solution was mixed in an amount of 0.4 g (0.005 mole) into the resultant reaction liquid in the reaction vessel, the resultant mixture was stirred for 30 minutes to neutralize the reaction liquid. From the reaction liquid, precipitated crystals were separated by filtration. A glycerol monohydroxydodecyl ether mixture was obtained in an amount of 55.3 g (yield: 96.7%)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[N:25](COCC[Si](C)(C)C)[C:24]([O:34][C@H:35]3[C@H:39]4[O:40][CH2:41][C@@H:42]([OH:43])[C@H:38]4[O:37][CH2:36]3)=[N:23][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=1.Br[C:45]1[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[C:47]([F:53])[CH:46]=1.N#N.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CS(C)=O.[Pd+2]>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:25][C:24]([O:34][C@H:35]3[C@H:39]4[O:40][CH2:41][C@@H:42]([OH:43])[C@H:38]4[O:37][CH2:36]3)=[N:23][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:45]2[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[C:47]([F:53])[CH:46]=2)=[CH:10][CH:9]=1
Reactant: COc1cc(F)cc(Br)c1
Reactant: CC1(C)OB(c2ccc(-c3nc4nc(O[C@@H]5CO[C@H]6[C@@H]5OC[C@H]6O)n(COCC[Si](C)(C)C)c4cc3Cl)cc2)OC1(C)C
Agent: [Pd+2]
Agent: N#N
Agent: O=P([O-])([O-])[O-]
Solvent: C1COCCO1
Solvent: CS(C)=O
Product: COc1cc(F)cc(-c2ccc(-c3nc4nc(O[C@@H]5CO[C@H]6[C@@H]5OC[C@H]6O)[nH]c4cc3Cl)cc2)c1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
(3R,3aR,6R,6aR)-6-((6-chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethyl-silyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (40 mg, 0.063 mmol) and 1-bromo-3-fluoro-5-methoxybenzene (15.62 mg, 0.076 mmol) in anhydrous dioxane (0.4 ml) was purged with N2 and then chloro[tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II) (6.5 mg, 0.013 mmol) and tripotassium phosphate (0.191 ml, 0.191 mmol) were added under N2 flow. The mixture was heated to 60° C. overnight. Then the crude mixture was extracted with DCM. The combined organic extracts were washed with water and evaporated under reduced pressure. 1 mL of 1:1 CH2Cl2 and TFA was added to the resulting residue and the solution was stirred for 2 h. Then the solvent was evaporated under reduced pressure to give an amber residue. The residue was diluted with 1.5 ml DMSO, filtered and purified by mass directed reverse phase column chromatography eluting with acetonitrile/water+0.1% TFA to give the title product. LC-MS: calculated for C25H21ClFN3O5, 497.12, observed m/e: 498.11 (M+H)+ (RT 1.03/2.00 min)
Reaction SMILES: [C:1]([C:3]1([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=2)[CH2:8][CH2:7][N:6]([CH2:9][C:10]([NH2:12])=[O:11])[CH2:5][CH2:4]1)#[N:2]>[Pt].CO.C(Cl)Cl>[NH2:19][C:16]1[CH:15]=[CH:14][C:13]([C:3]2([C:1]#[N:2])[CH2:4][CH2:5][N:6]([CH2:9][C:10]([NH2:12])=[O:11])[CH2:7][CH2:8]2)=[CH:18][CH:17]=1
Reactant: N#CC1(c2ccc([N+](=O)[O-])cc2)CCN(CC(N)=O)CC1
Agent: [Pt]
Solvent: CO
Solvent: ClCCl
Product: N#CC1(c2ccc(N)cc2)CCN(CC(N)=O)CC1
Yield: 98.9 %

Procedure:
2-[4-Cyano-4-(4-nitro-phenyl)-piperidin-1-yl]-acetamide (0.644 g, 2.23 mmol) was shaken over 5% Platinum on Carbon, Sulfided (0.5%) (94 mg, 0.024 mmol) in Methanol (10.0 mL) under an atmosphere of Hydrogen (40 psi) for 5 h. The precipitate was solubilized in DCM and then filtered to remove catalyst, washing with DCM. Conc. in vacuo to give 2-[4-(4-Amino-phenyl)-4-cyano-piperidin-1-yl]-acetamide (0.570 g; Yield=98.8) as an off white solid. 1H-NMR (DMSO-d6): 7.29 (s, 1H), 7.14 (m, 3H), 6.58 (d, 2H, J=8.4 Hz), 5.17 (s, 2H), 3.17 (d, 1H, J=5.2 Hz), 2.92 (s, 2H), 2.90 (m, 2H), 2.39 (m, 2H), 2.00 (m, 4H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[CH2:17][CH:18]([OH:21])[CH2:19][OH:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>N1C=CC=CC=1>[CH3:32][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O:20][CH2:19][CH:18]([OH:21])[CH2:17][C:10]2[CH:11]=[CH:12][C:13]([O:15][CH3:16])=[CH:14][C:9]=2[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)(=[O:30])=[O:29])=[CH:24][CH:23]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COc1ccc(CC(O)CO)c(OCc2ccccc2)c1
Solvent: c1ccncc1
Product: COc1ccc(CC(O)COS(=O)(=O)c2ccc(C)cc2)c(OCc2ccccc2)c1
Temperature: 0 °C
Reaction time: 12 h
Yield: 91.3 %

Procedure:
To a solution of (±)-3-[2-(benzyloxy)-4-methoxyphenyl]propane-1,2-diol (30.50 g, 0.106 mol) in anhydrous pyridine (600 mL) cooled to 0° C. under a nitrogen atmosphere was added p-toluenesulfonyl chloride (22.18 g, 0.116 mol). The reaction mixture was allowed to stir at 0° C. for 12 h. The reaction mixture was quenched by the addition of water (10 mL). The reaction mixture was diluted with ethyl acetate (750 mL) and the organic layer was washed with aqueous hydrogen chloride (6 N, 4×400 mL), saturated aqueous sodium chloride (300 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:8) gave 42.84 g (91%) of (±)-3-[2-(benzyloxy)-4-methoxyphenyl]-2-hydroxypropyl 4-methylbenzenesulfonate as a colorless oil. Rf=0.28 (silica, ethyl acetate:hexanes 2:8); Anal. calcd. for C24H26O6S: C, 65.14; H, 5.92. Found: C, 64.59; H, 5.72.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][C:3]=1[N:12]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N:23]3[CH2:28][CH2:27][N:26]([CH2:29][CH3:30])[CH2:25][CH2:24]3)[CH:19]=2)[N:14]=[CH:13]1.[OH-].[Na+]>>[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N:12]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N:23]3[CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH2:28]3)[CH:19]=2)[N:14]=[CH:13]1
Reactant: CCN1CCN(c2ccc3ncn(-c4cc(C(=O)OC)ccc4C)c(=O)c3c2)CC1
Agent: [Na+]
Agent: [OH-]
Product: CCN1CCN(c2ccc3ncn(-c4cc(C(=O)O)ccc4C)c(=O)c3c2)CC1

Procedure:
Using an analogous procedure to that described paragraph (C) in the portion of Example 1 which is concerned with the preparation of starting material methyl 4-methyl-3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoate was hydrolysed with 1N NaOH to give 4-methyl-3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid; NMR Spectrum: (DMSOd6) 1.30 (t, 3H), 2.16 (s, 3H), 3.20 (m, 6H), 3.59 (d, 2H), 4.03 (d, 2H), 7.60 (m, 2H), 7.71 (m, 2H), 7.93 (s, 1H), 8.01 (d, 1H), 8.15 (s, 1H), 10.48 (s, 1H), 13.11 (s, 1H); Mass Spectrum: M+H+ 393.
Reaction SMILES: [CH2:1]([C:4]1[C:5]([Cl:16])=[N:6][CH:7]=[N:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1)[CH:2]=C.C[N+]1([O-])CC[O:21]CC1>O1CCOCC1.[Os](=O)(=O)(=O)=O>[Cl:16][C:5]1[C:4]([CH2:1][CH:2]=[O:21])=[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[N:8]=[CH:7][N:6]=1
Reactant: C=CCc1c(Cl)ncnc1-c1ccccn1
Reactant: C[N+]1([O-])CCOCC1
Agent: O=[Os](=O)(=O)=O
Solvent: C1COCCO1
Product: O=CCc1c(Cl)ncnc1-c1ccccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 69.4 %

Procedure:
To a stirred solution of 5-allyl-4-chloro-6-(pyridin-2-yl)pyrimidine (1 g) in dry dioxane (10 mL), N-methyl morpholine N-oxide (0.75 g) and osmium tetroxide (0.35 mL, 25% solution in water) were added. The reaction mixture was stirred at room temperature for 2 hours before being quenched by solid sodium bisulphate. The reaction mixture was filtered through celite bed and the celite bed was washed with dioxane (5 mL). The combined filtrate was taken into a 100 mL three necked round bottom flask and sodium metaperiodate (2.3 g, in 5 mL water) was added. The reaction mixture was stirred at room temperature for 3 hours and then diluted with water (30 mL). Aqueous layer was extracted with dichloromethane (2×25 mL). The combined organic layer was washed with brine (50 mL) and dried over anhydrous Na2SO4. Evaporation of solvents under reduced pressure gave crude 2-(4-chloro-6-(pyridin-2-yl)pyrimidin-5-yl)acetaldehyde (0.7 g) which was used as was. 1H NMR (DMSO-d6): δ 4.12 (s, 2H), 7.53-7.55 (m, 1H), 7.88-8.01 (m, 2H), 8.66-8.69 (d, 1H), 8.97 (s, 1H), 9.79 (s, 1H).
Reaction SMILES: [CH:1]1([C:4]([O:6][CH2:7][CH2:8][O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=2)=[O:5])[CH2:3][CH2:2]1.S(Cl)([Cl:21])=O.CN(C)C=O>CCOCC>[CH:1]1([C:4]([O:6][CH2:7][CH2:8][O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14]([Cl:21])=[O:15])=[CH:12][CH:11]=2)=[O:5])[CH2:3][CH2:2]1
Reactant: O=C(O)c1ccc(OCCOC(=O)C2CC2)cc1
Reactant: O=S(Cl)Cl
Solvent: CCOCC
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(OCCOC(=O)C2CC2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a mixture of 3.2 g (12.8 mmol) of 4-(2-cyclopropylcarbonyloxyethoxy)benzoic acid, 80 ml of ether and 1.5 ml (20.5 mmol) of thionyl chloride, at RT, is added 0.3 ml (3.8 mmol) of dimethylformamide. This mixture is stirred, at RT, for 1 day. The top phase is decanted (the residue is discarded), and solvent and ohter volatiles are removed from it by rotoevaporation to give 4-(2-cyclopropylcarbonyloxyethoxy)benzoic acid chloride.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][C:13]([OH:15])=O)=[O:5])[CH3:2].[NH2:16][CH2:17][C:18]1([OH:25])[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>ClCCl.CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][C:13](=[O:15])[NH:16][CH2:17][C:18]1([OH:25])[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(C)c[nH]c1CC(=O)O
Reactant: CN1CCC(O)(CN)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCOC(=O)c1c(C)c[nH]c1CC(=O)NCC1(O)CCN(C)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 149.5 %

Procedure:
A solution of 2-carboxymethyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (3.717 g, 17.62 mmol) in dichloromethane (91 ml) in an ice-water bath was added with 4-aminomethyl-1-methyl-piperidin-4-ol (4 g, 19.38 mmol), N,N′-dimethylformamide (9.1 ml), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (8.751 g, 45.6 mmol) and 1-hydroxybenzotriazol (3,577 g, 26.5 mmol). Upon completion of the addition, the resulting mixture was stirred at room temperature overnight. The mixture was added with ice to quench the reaction, and washed with saturated potassium carbonate solution (10 ml×3) with brine (50 ml×3) The resulting mixture was partitioned and the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-{[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-carbamoyl]-methyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (8.891 g) as a brown oil, which was used as such.
Reaction SMILES: [C:1]([NH:4][C@H:5]([C:7]1[CH:26]=[CH:25][C:10]([CH2:11][N:12]2[CH2:21][CH2:20][C:19]3[C:18]([C:22]([OH:24])=O)=[CH:17][CH:16]=[CH:15][C:14]=3[CH2:13]2)=[CH:9][CH:8]=1)[CH3:6])(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:58]([NH2:65])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1>CN(C=O)C>[CH2:58]([NH:65][C:22]([C:18]1[C:19]2[CH2:20][CH2:21][N:12]([CH2:11][C:10]3[CH:25]=[CH:26][C:7]([C@@H:5]([NH:4][C:1](=[O:3])[CH3:2])[CH3:6])=[CH:8][CH:9]=3)[CH2:13][C:14]=2[CH:15]=[CH:16][CH:17]=1)=[O:24])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1
Reactant: CC(=O)N[C@@H](C)c1ccc(CN2CCc3c(cccc3C(=O)O)C2)cc1
Reactant: NCc1ccccc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(=O)N[C@@H](C)c1ccc(CN2CCc3c(cccc3C(=O)NCc3ccccc3)C2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
80 mg (0.15 mmol, 65%) 2-[4-((S)-1-Acetylamino-ethyl)-benzyl]-1,2,3,4-tetrahydro-isoquinoline-5-carboxylic acid (example XXXVII), 51 μL (0.30 mmol) DIPEA and 95 mg (0.30 mmol) TBTU in 1 mL DMF are stirred at r.t. for 10 min. Then 16 mg (0.15 mmol) benzylamine and 63 μL (0.37 mmol) DIPEA are added and the resulting mixture is stirred at r.t. for 2 h. After that time, the reaction is quenched by the addition of 200 μL water and purified by HPLC.
Reaction SMILES: [Li]CCCC.BrC1C=[CH:11][C:10]2[C:13]3[C:18]([C:19]4([CH:27]=[C:26]5[C:21]([C:22]([C:34]6[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=6)=[CH:23][CH:24]=[C:25]5[C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[CH:20]4)[C:9]=2C=1)=[CH:17][CH:16]=[CH:15][CH:14]=3.[CH:40]([B:43]1[O:47][C:46]([CH3:49])([CH3:48])[C:45]([CH3:51])([CH3:50])[O:44]1)([CH3:42])[CH3:41].O>C1COCC1.CCOCC>[C:34]1([C:22]2[C:21]3[C:26]([C:25]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:24][CH:23]=2)=[CH:27][C:19]2([C:9]4[CH:42]=[C:40]([B:43]5[O:47][C:46]([CH3:49])([CH3:48])[C:45]([CH3:51])([CH3:50])[O:44]5)[CH:41]=[CH:11][C:10]=4[C:13]4[C:18]2=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH:20]=3)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: Brc1ccc2c(c1)C1(C=c3c(-c4ccccc4)ccc(-c4ccccc4)c3=C1)c1ccccc1-2
Reactant: CC(C)B1OC(C)(C)C(C)(C)O1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Solvent: C1CCOC1
Product: CC1(C)OB(c2ccc3c(c2)C2(C=c4c(-c5ccccc5)ccc(-c5ccccc5)c4=C2)c2ccccc2-3)OC1(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 79 %

Procedure:
n-BuLi (1.2 equiv) is added to a solution of 2-bromo-4′,7′-diphenylspiro(fluorene-9,2′-indene) (6b) in anhydrous THF at −78° C. After stirring the mixture for 1 h, 2-isopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 equiv) is added. The reaction mixture is allowed to warm to room temperature and then is stirred overnight. The reaction mixture is mixed with a large amount of water for extraction with ether. The organic extracts are washed with brine before drying over anhydrous MgSO4. The crude product of 2-[4′,7′-diphenylspiro(fluorene-9,2′-inden)-2-yl]-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane (7b) is purified by column chromatography on silica gel using methylene chloride as the eluent yielding a white powder (79%).