Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C:3]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4]1.Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(N(CC)CC)C.O>ClCCl>[CH2:12]([O:11][C:9]([N:6]1[CH2:7][CH2:8][C:3]([CH2:2][NH:1][C:22]([O:24][CH2:25][CH3:26])=[O:23])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[CH2:4][CH2:5]1)=[O:10])[CH3:13]
Reactant: CCOC(=O)N1CCC(CN)(c2ccccc2C)CC1
Reactant: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)NCC1(c2ccccc2C)CCN(C(=O)OCC)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51 %

Procedure:
Subsequently, the obtained 4-aminomethyl-1-(ethoxycarbonyl)-4-(2-methylphenyl)piperidine was dissolved in dichloromethane (10 ml), added with ethyl chloroformate (0.18 ml) and triethylamine (0.26 ml) and stirred at room temperature for 30 minutes. The reaction mixture was added with water (10 ml), and the layers were separated. Then, the aqueous layer was further extracted with dichloromethane (10 ml). The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: hexane:ethyl acetate=2:1) to obtain 372 mg of the title compound. Yield: 51% (for the two steps).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([NH2:5])=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:17])=CC=1.Br[CH2:31][C:32](=O)[C:33]([O:35][CH2:36][CH3:37])=[O:34]>C1COCC1>[F:1][C:2]([F:7])([F:6])[C:3]1[S:17][CH:31]=[C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[N:5]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CCOC(=O)C(=O)CBr
Reactant: NC(=O)C(F)(F)F
Solvent: C1CCOC1
Product: CCOC(=O)c1csc(C(F)(F)F)n1
Temperature: 25 °C
Yield: 52.5 %

Procedure:
A mixture of 2,2,2-trifluoroacetamide (7.12 g, 63 mmol) and Lawesson's reagent (15.3 g, 37.8 mmol) in THF (60 mL) was heated at reflux for 18 hours. The reaction was then cooled down to RT and treated with ethyl bromopyruvate (8.0 mL, 63 mmol). The reaction was stirred at reflux for an additional 18 hours, then concentrated under vacuum and diluted with ethyl acetate. This mixture was washed with water (1×) and brine (1×), dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (8×11 cm, toluene, then second time with 120 g silica gel, hexane/ethyl acetate) to give the title material (4.47 g, 32%) as a pale yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.37 (s, 1H), 4.45 (q, J=7.0 Hz, 2H), 1.41 (t, J=7.0 Hz, 1H).
Reaction SMILES: [N:1]([C@@:4]([C:9]([OH:11])=[O:10])([CH:6]([CH3:8])[CH3:7])N)=[C:2]=[O:3].[CH3:12][N:13]([C:15]1[S:16][CH:17]=[C:18]([CH2:20][NH:21][CH3:22])[N:19]=1)[CH3:14].Cl[CH2:24]Cl>>[CH3:24][O:11][C:9](=[O:10])[C@H:4]([CH:6]([CH3:8])[CH3:7])[NH:1][C:2]([N:21]([CH3:22])[CH2:20][C:18]1[N:19]=[C:15]([N:13]([CH3:12])[CH3:14])[S:16][CH:17]=1)=[O:3]
Reactant: CNCc1csc(N(C)C)n1
Reactant: CC(C)[C@@](N)(N=C=O)C(=O)O
Reactant: ClCCl
Product: COC(=O)[C@@H](NC(=O)N(C)Cc1csc(N(C)C)n1)C(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 34 %

Procedure:
A solution of 741 mg (4.42 mmol) of α-isocyanato-L-valine in in 5 ml of dichloromethane was added to a solution of 720 mg (4.21 mmol) of 2-(N,N-dimethylamino)-4-(((N-methyl)amino)methyl)thiazole in 25 ml of dichloromethane. The resulting solution was stirred at ambient temperature for 16 h, partitioned between chloroform and aqueous NaHCO3, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel chromatography using 2% methanol in chloroform to provide 463 mg (34%) of the desired compound, Rf 0.25 (2% methanol in chloroform). NMR (CDCl3) δ 0.96 (d, J=7 Hz, 3 H), 0.98 (d, J=7 Hz, 3 H), 2.13 (m, 1 H), 2.97 (s, 3 H), 3.11 (s, 6 H), 3.71 (s, 3 H), 4.07 (br d, J=16 Hz, 1 H), 4.34 (dd, J=9, 5 Hz, 1 H), 4.42 (d, J=16 Hz, 1 H), 6.29 (s, 1 H), 6.37 (br, 1 H). Mass spectrum: (M+H)+ =329.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].Br[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[O:22][CH:23]=[C:24]([CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][CH:28]3[CH3:32])[N:25]=2)=[CH:17][CH:16]=1.Cl>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[O:22][CH:23]=[C:24]([CH2:26][N:27]4[CH2:31][CH2:30][CH2:29][CH:28]4[CH3:32])[N:25]=3)=[CH:17][CH:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc(B(O)O)cc1
Reactant: CC1CCCN1Cc1coc(-c2ccc(Br)cc2)n1
Agent: Cl
Product: CC1CCCN1Cc1coc(-c2ccc(-c3ccc(S(C)(=O)=O)cc3)cc2)n1

Procedure:
The titled compound is prepared substantially in accordance with the procedure of Example 4 using 4-methylsulfonylphenylboronic acid and (+/−)-2-(4-Bromo-phenyl)-4-(2-methyl-pyrrolidin-1-ylmethyl)-oxazole; hydrochloride (See Example 5). MS (m/e) 397.1 (M+1)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[NH:5][C:6]1[C:7]2[CH:14]=[C:13]([CH:15]=O)[NH:12][C:8]=2[N:9]=[CH:10][N:11]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>CO.CN1C(=O)N(C)CCC1.C(O)(=O)C.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[NH:5][C:6]1[C:7]2[CH:14]=[C:13]([CH2:15][N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[NH:12][C:8]=2[N:9]=[CH:10][N:11]=1
Reactant: C1COCCN1
Reactant: O=Cc1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1
Agent: [Ni]
Solvent: CC(=O)O
Solvent: CO
Solvent: CN1CCCN(C)C1=O
Product: Clc1cccc(Nc2ncnc3[nH]c(CN4CCOCC4)cc23)c1

Procedure:
109 mg (0.40 mmol) of 4-(3-chloroanilino)-6-formyl-7H-pyrrolo[2,3-d]pyrimidine (stage 1.6) and 70 μl (0.8 mmol) of morpholine in 6 ml of methanol, 2 ml of DMPU and 50 μl of acetic acid are heated at 50° C. for 2 h. 30 mg of Raney nickel are then added and the mixture is hydrogenated at 50° C. The catalyst is filtered off, the filtrate is evaporated and the residue is dissolved in ethyl acetate and satd Na2CO3 solution. The aqueous phase separated off is extracted twice with ethyl acetate; the organic phases are washed with satd NaHCO3 solution, twice with water and brine, dried (MgSO4) and evaporated. The residue is taken up in methanol, and the solution is treated with silica gel and dried. The powder is added to a silica gel column and eluted with CH2Cl2/methanol=10:1. Crystallization from ethyl acetate/diethyl ether/hexane yields 4-(3-chloroanilino)-6-[(morpholin-4-yl)-methyl]-7H-pyrrolo[2,3-d]pyrimidine; m.p: 244-246° C.; HPLC: tRet(Grad20)=7.4; TLC-Rf=0.20 (CH2Cl2/methanol 10:1); FAB-MS: (M+H)+=344.
Reaction SMILES: [C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13]C)[CH:11]=2)[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([O:21]C)=[CH:17][CH:16]=2)[CH:4]=1)#[N:2].N1C(=O)CC[C@H]1C(O)=O.Br>>[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([OH:13])[CH:11]=2)[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[CH:4]=1)#[N:2]
Reactant: COc1ccc(-c2cc(C#N)c3cc(OC)ccc3n2)cc1
Agent: Br
Agent: O=C1CC[C@@H](C(=O)O)N1
Product: N#Cc1cc(-c2ccc(O)cc2)nc2ccc(O)cc12
Yield: 89 %

Procedure:
This compound was prepared from 9a using Pyr./HBr according to method I. Yellow solid; Yield: 89%; mp>240° C. (dec.); 1H-NMR (300 MHz, DMSO-d6) δ 6.92 (d, J=8.7 Hz, 2H), 7.30 (d, J=2.6 Hz, 1H), 7.45 (dd, J=9.1, 2.6 Hz, 1H), 8.02 (d, J=9.1 Hz, 1H), 8.13 (d, J=8.7 Hz, 2H), 8.58 (s, 1H), 9.93 (s, 1H), 10.64 (s, 1H): MS (ESI) m/z 261 ([M−H]−), 263 ([M+H]+); Anal. Calcd for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68. Found: C, 71.75; H, 3.86; N, 10.14.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10](=[N:19][NH2:20])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2F)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:11]3[C:16](=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[NH:20][N:19]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCC(C(=NN)c2ccc(Cl)cc2F)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)N1CCC(c2n[nH]c3cc(Cl)ccc23)CC1
Temperature: 120 °C
Reaction time: 16 h
Yield: 20.8 %

Procedure:
A mixture of 19.6 g of 1-acetyl-4-(2-fluoro-4-chlorobenzoyl)piperidine hydrazone, 18.2 g of potassium carbonate and 200 ml of dimethylformamide was stirred, under nitrogen, at 120° C. for 16 hrs. After cooling to ambient temperature, the reaction mixture was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated to an oil. Upon standing, a solid formed. The solid was triturated with ethyl acetate to yield 3.8 g (21%) of product. Recrystallization from acetonitrile gave the analytical sample, mp 172°-174° C.
Reaction SMILES: [NH2:1][C:2]1[N:3]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:4]=[C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]#[CH:13])[N:6]=1.[N:21]([CH2:24][CH2:25][NH:26][S:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:29])=[O:28])=[N+:22]=[N-:23]>>[NH2:1][C:2]1[N:3]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:4]=[C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]2[N:23]=[N:22][N:21]([CH2:24][CH2:25][NH:26][S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:28])=[O:29])[CH:13]=2)[N:6]=1
Reactant: [N-]=[N+]=NCCNS(=O)(=O)c1ccccc1
Reactant: C#CCCCCCc1cn(C(=O)OC(C)(C)C)c(N)n1
Product: CC(C)(C)OC(=O)n1cc(CCCCCc2cn(CCNS(=O)(=O)c3ccccc3)nn2)nc1N

Procedure:
tert-butyl 2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.114 g, 0.410 mmol) was reacted with N-(2-azidoethyl)benzenesulfonamide (0.104 g, 0.410 mmol) following the general click procedure to give tert-butyl 2-amino-4-(5-(1-(2-(phenylsulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate 1H NMR (300 MHz, CDCl3) δ 7.81 (d, 2H), δ 7.44 (m, 5H), δ 6.44 (s, 1H), δ 6.07 (s, 2H), δ 4.42 (t, 2H), δ 3.36 (t, 2H), δ 2.47 (t, 2H), δ 2.20 (s, 2H), δ 1.47 (m, 13H0, δ 1.29 (s, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 202.9, 149.5, 148.2, 140.2, 132.8, 129.4, 127.1, 122.5, 106.5, 85.0, 53.7, 50.3, 42.9, 32.7, 31.2, 29.9, 29.2, 28.9, 28.2, 26.3, 25.5 ppm; HRMS (ESI) calcd for C23H33N7O4S (M+) 503.2315, found 503.2310, which was subsequently deprotected to give tert-butyl 2-amino-4-(5-(1-(2-(phenylsulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate hydrochloride (0.142 g, 64% yield). 1H NMR (300 MHz, CD3OD) δ 7.81 (d, 2H), δ 7.56 (m, 4H), δ 6.47 (s, 1H), δ 4.62 (s, 2H), δ 3.41 (s, 2H), δ 2.78 (s, 2H), δ 2.48 (s, 2H), δ 1.72 (s, 2H), δ 1.63 (s, 2H), δ 1.42 (s, 2H) ppm; 13C NMR (75 MHz, CD3OD) δ 176.2, 165.6, 159.9, 147.3, 140.2, 132.8, 129.3, 127.7, 126.8, 108.5, 108.4, 515.8, 42.3, 28.1, 27.9, 27.6, 24.1 ppm; HRMS (ESI) calcd for C18H25N7O2S (M+) 403.1790, found 403.1781.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[NH:9][C:10]([NH:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:20])=S.CI>C(O)C>[ClH:19].[Cl:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[NH:12][C:10]1[NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=2[N:9]=1
Reactant: Nc1cccc(O)c1NC(=S)Nc1c(Cl)cccc1Cl
Solvent: CI
Solvent: CCO
Product: Cl
Product: Oc1cccc2[nH]c(Nc3c(Cl)cccc3Cl)nc12
Temperature: 25 °C
Yield: 47 %

Procedure:
Intermediate 1 was dissolved in ethanol and treated with 8 equivalents of methyl iodide. The mixture was heated to reflux for 8 h. After it cooled to RT, the reaction solution was filtered through activated carbon and the filtrate was concentrated in vacuo. The residue was treated with 0.5 N HCl and the precipitate was filtered off with suction after 30 min. The residue was stirred once more with EA and dried. The title compound was isolated in a yield of 47%. M.p.: 333-335° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.N1C=CC=CC=1.Cl[C:14]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:15].C(=O)(O)[O-].[Na+]>ClCCl>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[NH:1][C:14](=[O:15])[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Nc1nccs1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(Nc1nccs1)Oc1ccccc1
Reaction time: 0.5 h
Yield: 75 %

Procedure:
To a stirred mixture of 2-aminothiazole (2 g, 20 mmol), pyridine (10 mL), and anhydrous dichloromethane (20 mL) was added phenyl chloroformate (3 mL, 24 mmol) under argon at 0° C. The mixture was stirred at the same temperature for 5 min and at rt overnight before saturated aqueous sodium bicarbonate solution (30 mL) was added slowly. After mixed with heptanes (30 mL), the mixture was stirred for 30 min. The solid was filtered, washed with water (3×3 mL) and then diethylether (3×3 mL), and dried to give phenyl thiazol-2-ylcarbamate (3.4 g, 15 mmol, 75% yield) as an off-white solid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][OH:22])[CH2:17][CH2:16]1)=[O:14].C(N(CC)CC)C>ClCCl>[CH3:11][O:12][C:13]([N:15]1[CH2:16][CH2:17][CH:18]([CH:21]=[O:22])[CH2:19][CH2:20]1)=[O:14]
Reactant: COC(=O)N1CCC(CO)CC1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: COC(=O)N1CCC(C=O)CC1
Temperature: -10 °C
Reaction time: 0.08 h
Yield: 77.3 %

Procedure:
To a solution of oxalyl chloride (4.1 mL, 8.2 mmol) in dichloromethane (4 mL) at −78° C. was added dropwise a solution of dimethylsulfoxide (1.2 mL, 16.4 mmol) in dichloromethane (4 mL). After stirring for 5 min, a solution of 4-hydroxymethyl-piperidine-1-carboxylic acid methyl ester (1.3 g, 7.5 mmol) in dichloromethane (5 mL) was added. The resulting solution was stirred for another 5 min, then triethylamine (5.2 mL, 37.3 mmol) was added and the mixture allowed to warm to −10° C. After stirring for 1 h, dichloromethane (100 mL) was added, and the organic layer was washed with 1M aqueous phosphoric acid, 1M aqueous sodium hydroxide, and brine. The solution was dried over sodium sulfate then evaporated to afford the title intermediate as a wheat colored oil (1.0 g, 5.8 mmol, 78%). 1H NMR (300 MHz, DMSO-d6): δ (ppm) 1.36 (m, 2H), 1.83 (m, 2H), 2.48 (br m, 1H), 2.93 (br t, 2H), 3.56 (s, 3H), 3.80 (br d, 2H), 9.56 (s, 1H).
Reaction SMILES: [CH3:1][CH:2]1[C:6](=[O:7])[C:5]([OH:8])=[C:4]([CH3:9])[O:3]1.C(N(CC)CC)C.Cl[C:18]([O:20][CH2:21][CH3:22])=[O:19]>C(Cl)Cl>[C:18](=[O:19])([O:7][C:6]1[C:5](=[O:8])[CH:4]([CH3:9])[O:3][C:2]=1[CH3:1])[O:20][CH2:21][CH3:22]
Reactant: CC1=C(O)C(=O)C(C)O1
Reactant: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)OC1=C(C)OC(C)C1=O
Yield: 72.5 %

Procedure:
A solution of 2,5-dimethyl-4-hydroxy-3(2H)-furanone (pineapple ketone, 133.0 g, 1.0 mole) and triethylamine (152.0 g, 1.5 moles) in methylene chloride (665 g) is cooled to 5° C. under nitrogen atmosphere. To the cooled solution is added over a period of 2.5 hours, a solution of ethyl chloroformate (127.7 g, 1.18 moles) in methylene chloride (600 g) stirred at 5°-8° C. for two additional hours. The reaction mixture is filtered through a Buchner funnel to remove the triethylamine hydrochloride. The salt is washed with methylene chloride (200 ml). The combined organic layers are washed twice with 100 ml portions of water and dried over sodium sulfate. The solvent is removed in vacuo and the crude product distilled (<0.1 torr) through a Goodloe column to yield 72.5% of ethyl 2,5-dimethyl-3-oxo-4(2H)-furyl carbonate product b.p. 87° C. (0.08 torr), IR (neat film) 2980(M), 1770(S), 1715(S), 1640(S), 1250(S) cm-1, 'H NMR δ1.58(t.J=8 Hz,3), 1.65 (d,J=7Hz,3), 2.32 (s,3), 4.45 (q,J=7Hz,2), 4.75 (q,J=7Hz,1), and 3.3% of the diadduct, diethyl 2,5-dimethyl-3,4-furyl dicarbonate, b.p. 110° C. (0.08 torr), IR (neat film 2980(M), 1770(S), 1250(S), 'H NMR δ=1.50 (t,J=6 Hz,6) 2.3 (S,6) 4.45 (q,J=8 Hz,4).
Reaction SMILES: [N:1]1([C:5]2[N:10]=[CH:9][C:8]([NH:11][C:12]([C:14]3[N:15]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=4)[C:16]4[C:21]([CH:22]=3)=[CH:20][C:19](Br)=[CH:18][CH:17]=4)=[O:13])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH2:32]([SiH:34]([CH2:36][CH3:37])C)[CH3:33].[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].[CH3:56]N1CCCC1=O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[N:1]1([C:5]2[N:10]=[CH:9][C:8]([NH:11][C:12]([C:14]3[N:15]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=4)[C:16]4[C:21]([C:22]=3[SiH:34]([CH2:36][CH3:37])[CH2:32][CH3:33])=[CH:20][C:19]([CH3:56])=[CH:18][CH:17]=4)=[O:13])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Nc1ccc(N2CCC2)nc1)c1cc2cc(Br)ccc2n1Cc1cccc(F)c1
Reactant: CN1CCCC1=O
Reactant: CC[SiH](C)CC
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: O=P([O-])([O-])OP(=O)([O-])OP(=O)([O-])[O-]
Agent: [K+]
Product: CC[SiH](CC)c1c(C(=O)Nc2ccc(N3CCC3)nc2)n(Cc2cccc(F)c2)c2ccc(C)cc12

Procedure:
Compound No. 22 was prepared according to a process similar to that described in stage 8.4, by reacting 0.15 g (0.31 mmol) of N-[6-(azetidin-1-yl)pyridin-3-yl]-5-bromo-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxamide, prepared according to the protocol described in stage 17.3, with 95 mg (0.93 mmol) of diethyl(methyl)silane in the presence of 0.2 g (0.94 mmol) of potassium triphosphate and of 16 mg (0.03 mmol) of bis(tri-tert-butylphosphine)palladium in 2 ml of dry 1-methyl-2-pyrrolidinone (NMP). 13 mg of the expected product are obtained.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:15](=[O:17])[CH3:16].[O:18]1[CH2:23][CH2:22][CH2:21][C:20](=O)[CH2:19]1.N1CCCC1>C1(C)C=CC=CC=1>[O:8]([C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[O:1][C:20]1([CH2:21][CH2:22][CH2:23][O:18][CH2:19]1)[CH2:16][C:15]2=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(=O)c1cc(Oc2ccccc2)ccc1O
Reactant: O=C1CCCOC1
Solvent: Cc1ccccc1
Solvent: C1CCNC1
Product: O=C1CC2(CCCOC2)Oc2ccc(Oc3ccccc3)cc21
Yield: 51.4 %

Procedure:
To a solution of 1-(2-hydroxy-5-phenoxyphenyl)ethanone (2.0 g, 8.77 mmol) in toluene (30 mL) was added dihydro-2H-pyran-3(4H)-one (1.14 g, 11.40 mmol) and pyrrolidine (0.81 g, 11.40 mmol), and the reaction mixture was refluxed overnight. After cooling, the mixture was concentrated. The residue was washed with 1 N HCl, brine, dried and concentrated to give the crude product, which was purified by chromatography to afford 6-phenoxy-2′,4′,5′,6′-tetrahydrospiro[chroman-2,3′-pyran]-4-one (1.40 g, 52%). 1H-NMR (CDCl3): 0.79 (m, 1H), 1.52 (m, 2H), 1.67 (m, 1H), 1.92 (m, 1H), 2.08 (m, 1H), 2.57-2.61 (q, 2H), 3.51 (m, 2H), 3.88 (m, 2H), 6.89 (d, 2H), 7.03 (m, 2H), 7.18 (m, 1H), 7.26 (t, 2H), 7.39 (m, 1H).
Reaction SMILES: C([O:3][C:4](=[O:26])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[C:14](=[O:25])[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][C:18]=1[F:24])C.[OH-].[Na+].Cl>C(O)C.C(OCC)(=O)C>[Br:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][NH:15][C:14]([C:8]2[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:7]=2[O:6][CH2:5][C:4]([OH:26])=[O:3])=[O:25])=[C:18]([F:24])[CH:19]=1
Reactant: CCOC(=O)COc1cc(Cl)ccc1C(=O)NCc1ccc(Br)cc1F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CCOC(C)=O
Product: O=C(O)COc1cc(Cl)ccc1C(=O)NCc1ccc(Br)cc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97 %

Procedure:
A solution of [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid ethyl ester (3.20 g, 7.20 mmol) in ethanol (36 mL, 0.2 M) was cooled to 0° C. and treated with aq NaOH (1.25 M, 28.8 mL, 36.0 mmol). After stirring for 30 min, the solution was warmed to room temperature and stirred an additional 4 h. Next, the solution was acidified to pH 1-2 with 2 N HCl, diluted with ethyl acetate and washed with saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated to give [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-chloro-phenoxy]-acetic acid as a white crystalline solid (2.91 g, 97%): mp 184-185° C.; Rf 0.31 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 13.40 (br s, 1H), 9.05, (t, J=5.7 Hz, 1H), 7.83, (d, J=8.4 Hz, 1H), 7.48 (d, J=10.5 Hz, 1 Hz), 7.38-7.32 (m, 2H), 7.26 (d, J=1.8 Hz, 1H), 7.13 (dd, J1=8.4 Hz, J2=1.5 Hz, 1H), 4.91 (s, 2H), 4.49 (d, J=5.7 Hz, 2H). ESI-LC/MS m/z calcd for C16H12BrClFNO4: 416.6; found 418.0 (M+1)+. Anal. calcd for C16H12BrClFNO4: C, 46.13; H, 2.90; N, 3.36; Cl, 17.02. Found C, 46.04; H, 2.89; N, 3.31; Cl, 17.09.
Reaction SMILES: C([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[NH:5]1)(C)C.Cl[C:11]1[CH:16]=[CH:15][N:14]2[N:17]=[CH:18][CH:19]=[C:13]2[N:12]=1.Br[C:21]1C=NN2C=CC(Cl)=NC=12>>[CH3:21][CH:8]1[O:7][C:6](=[O:9])[N:5]([C:11]2[CH:16]=[CH:15][N:14]3[N:17]=[CH:18][CH:19]=[C:13]3[N:12]=2)[CH2:4]1
Reactant: Clc1ccn2ncc(Br)c2n1
Reactant: CC(C)[C@H]1COC(=O)N1
Reactant: Clc1ccn2nccc2n1
Product: CC1CN(c2ccn3nccc3n2)C(=O)O1
Yield: 48 %

Procedure:
5-Methyl-3-(pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (0.170 g, 48%) was prepared by the procedure described in Example 1, Step 4, substituting 5-methyloxazolidin-2-one (0.494 g, 4.88 mmol) for (S)-4-isopropyloxazolidin-2-one and 5-chloropyrazolo[1,5-a]pyrimidine (0.250 g, 1.63 mmol) for 3-bromo-5-chloropyrazolo[1,5-a]pyrimidine.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[C:7]([N+:11]#[C-:12])([CH3:10])([CH3:9])[CH3:8].[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=1[CH:16]=O>Cl(O)(=O)(=O)=O>[C:7]([NH:11][C:12]1[N:6]2[C:2]([S:3][CH:4]=[CH:5]2)=[N:1][C:16]=1[C:15]1[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=1[F:13])([CH3:10])([CH3:9])[CH3:8]
Reactant: [C-]#[N+]C(C)(C)C
Reactant: Nc1nccs1
Reactant: O=Cc1ccccc1F
Agent: [O-][Cl+3]([O-])([O-])O
Product: CC(C)(C)Nc1c(-c2ccccc2F)nc2sccn12

Procedure:
Compound 44 was prepared in accordance with the general synthesis instructions from 1.0 ml (0.1 mmol) 2-aminothiazole solution (0.1 M, MC), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, MC), 0.500 ml (0.15 mmol) 2-fluorobenzaldehyde solution (0.3 M, MC) and 10 μl perchloric acid (w=20%) in a substance library.
Reaction SMILES: [NH:1]1[C:5]([SH:6])=[N:4][N:3]=[N:2]1.[H-].[Na+].[S:9]1[CH:13]=C[CH:11]=[C:10]1CC(OCCl)=O.CN(C)C=[O:23]>Cl.O>[C:10]([S:9][CH2:13][S:6][C:5]1[NH:4][N:3]=[N:2][N:1]=1)(=[O:23])[CH3:11]
Reactant: Sc1nnn[nH]1
Reactant: CN(C)C=O
Reactant: O=C(Cc1cccs1)OCCl
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CC(=O)SCSc1nnn[nH]1
Reaction time: 0.09 h

Procedure:
To a solution of tetrazole-5-thiol (3.00 g : 29.41 mMol.) in dimethylformamide (50 ml) under ice cooling is added sodium hydride (60% suspension in oil : 2.59 q : 64.75 mMol.), and the mixture is stirred under ice cooling for 5 to 6 minutes. To the mixture is added a solution of chloromethyl thiolacetate (4.39 gi 35.26 mMol.) in dimethylformamide (10 ml), and the mixture is stirred at room temperature for 2 hours. The reaction mixture is diluted with 10% hydrochloric acid (11 ml) and water and extracted with ethyl acetate. The extract is washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue is purified by silica gel column chromatography (toluene : ethyl acetate=1:1) and the resulting residue is washed with a mixture of n-hexane and ether to give 5-acetylthiomethylthiotetrazole (2.49 9) as colorless crystals. Yield : 45%, m.p. 90° C.