Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.CCN(C(C)C)C(C)C.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](Cl)=[O:28]>C(Cl)Cl>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([N:2]([CH3:1])[CH2:3][CH2:4][C:5]#[C:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)=[O:28]
Reactant: CNCCC#Cc1ccccn1
Reactant: COc1cccc(C(=O)Cl)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1cccc(C(=O)N(C)CCC#Cc2ccccn2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.6 %

Procedure:
N-Methyl-4-(pyridin-2-yl)but-3-yn-1-amine (50 mg, 0.31 mmol) was dissolved in DCM (2 mL) and DIEA (67 μl, 0.41 mmol) was added at room temperature. The resulting mixture was cooled to 0° C. before the addition of 3-methoxybenzoyl chloride (69 mg, 0.41 mmol). After stirring overnight at room temperature, the mixture was quenched with water and extracted with DCM. DCM fractions were washed with water (10 mL), NaHCO3 sat (2*10 mL), water (10 mL), brine (10 mL). The solvent was removed and the crude residue was purified over silicagel chromatography (prepacked 10 g silicagel column, DCM/MeOH: from 100/0 to 95/5 as eluent) to afford 58 mg of 3-methoxy-N-methyl-N-(4-(pyridin-2-yl)but-3-ynyl)benzamide (Yield: 63%) as a brown oil.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[NH:12][C:13]1[N:21]=[C:20]([Cl:22])[N:19]=[C:18]2[C:14]=1[N:15]=[CH:16][N:17]2[CH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>O>[Cl:22][C:20]1[N:19]=[C:18]2[C:14]([N:15]=[CH:16][N:17]2[CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[C:13]([NH:12][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH2:4][CH2:3][CH2:2][N:32]2[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]2)[N:21]=1
Reactant: ClCCCOc1ccccc1Nc1nc(Cl)nc2c1ncn2C1CCCC1
Reactant: CN1CCNCC1
Solvent: O
Product: CN1CCN(CCCOc2ccccc2Nc2nc(Cl)nc3c2ncn3C2CCCC2)CC1

Procedure:
[2-(3-Chloro-propoxy)-phenyl]-(2-chloro-9-cyclopentyl-purin-6-yl)-amine (0.4 mmol) are stirred at RT in N-methylpiperazine (0.3 ml) for 12 hours. The mixture is diluted with water and extracted 3 times with ethyl acetate. The combined organic phases are washed with brine and the extract is dried over sodium sulfate and evaporated. The residue is purified by flash chromatography on silica gel with (CH2Cl2/MeOH=9:1) as mobile phase. The product containing fractions are combined and evaporated. A pale oil with R=0.25 (CH2Cl2/MeOH=9:2) is obtained.
Reaction SMILES: Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.[C:36](Cl)(=[O:38])[CH3:37]>C(Cl)Cl>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[S:16][C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH2:5][CH2:4][C@@H:3]4[NH:2][C:36](=[O:38])[CH3:37])=[N:13][N:14]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]
Reactant: CC(=O)Cl
Reactant: CC(C)Oc1ccc(-c2nnc(-c3cccc4c3CC[C@@H]4N)s2)cc1C#N
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N[C@H]1CCc2c(-c3nnc(-c4ccc(OC(C)C)c(C#N)c4)s3)cccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Prepared using General Procedure 7: To a stirred solution of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (15 mg, 0.03 mmol) in anhydrous DCM (1 mL) was added triethylamine (11 mg, 0.1 mmol) followed by acetyl chloride (4.2 mg, 0.05 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the crude mixture purified by preparative HPLC to afford (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)acetamide 14. LCMS-ESI (m/z) calculated for: C23H22N4O2S: 418.2; found 419.3 [M+H]+, tR=3.34 min. 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J=8.9, 2.3 Hz, 1H), 8.13 (d, J=2.2 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.36 (t, J=7.6 Hz, 1H), 7.08 (d, J=9.0 Hz, 1H), 5.83 (d, J=8.4 Hz, 1H), 5.57 (q, J=7.9 Hz, 1H), 4.76 (dt, J=12.2, 6.1 Hz, 1H), 3.46 (ddd, J=17.1, 8.8, 3.8 Hz, 1H), 3.28-3.15 (m, 1H), 2.75-2.62 (m, 1H), 2.07 (s, 3H), 1.98-1.80 (m, 1H), 1.46 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 170.36, 167.43, 166.14, 162.16, 145.92, 142.83, 133.89, 133.77, 129.44, 128.23, 127.18, 126.95, 123.21, 116.05, 114.36, 104.23, 73.03, 55.00, 34.03, 31.95, 23.92, 22.24.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:20][CH2:19][CH2:18][C@@H:17]3[N:12]2[C:13](=[O:21])[CH2:14][CH:15]=[CH:16]3)=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2].[H][H]>CO.[Pt]=O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:20][CH2:19][CH2:18][C@@H:17]3[N:12]2[C:13](=[O:21])[CH2:14][CH2:15][CH2:16]3)=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2]
Reactant: [H][H]
Reactant: COC(=O)c1ccc([C@H]2CCC[C@H]3C=CCC(=O)N32)cc1
Agent: O=[Pt]
Solvent: CO
Product: COC(=O)c1ccc([C@H]2CCC[C@H]3CCCC(=O)N32)cc1
Yield: 85.6 %

Procedure:
Platinum oxide (10 mg) was added to a solution of (6R*,9aS*)-6-(4-carbomethoxyphenyl)-3,6,7,8,9,9a-hexahydroquinolizin-4-one (145 mg) in methanol (5 mL), and the reaction solution was stirred in a hydrogen stream at room temperature for three hours. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure to obtain 125 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[C:10]([C:12]#[N:13])[CH:9]=[CH:8][N:7]=2)[N:3]=[CH:2]1.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][CH:22]1[CH2:26]Br)=[O:20])([CH3:17])([CH3:16])[CH3:15]>>[C:12]([C:10]1[CH:9]=[CH:8][N:7]=[C:6]([C:4]2[N:3]=[CH:2][N:1]([CH2:26][CH:22]3[CH2:23][CH2:24][CH2:25][N:21]3[C:19]([O:18][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:20])[CH:5]=2)[CH:11]=1)#[N:13]
Reactant: CC(C)(C)OC(=O)N1CCCC1CBr
Reactant: N#Cc1ccnc(-c2c[nH]cn2)c1
Product: CC(C)(C)OC(=O)N1CCCC1Cn1cnc(-c2cc(C#N)ccn2)c1

Procedure:
The title compound was prepared from 2-(1H-imidazol-4-yl)pyridine-4-carbonitrile and tert-butyl-2-(bromomethyl)pyrrolidine-1-carboxylate according to the procedure for the preparation of Example 43, part A (heating to 120°). [M+H] Calc'd for C19H23N5O2, 354. Found, 354.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[F:20])[C:11]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[F:30])([C:21]#[N:22])[CH:10]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[NH:9]1)=[O:7].[S:36](N)([NH2:39])(=[O:38])=[O:37].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH2:39][S:36]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[F:20])[C:11]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[F:30])([C:21]#[N:22])[CH:10]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[NH:9]1)=[O:7])(=[O:38])=[O:37]
Reactant: CC(C)(C)CC1NC(C(=O)NCCCN)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Reactant: NS(N)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)CC1NC(C(=O)NCCCNS(N)(=O)=O)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Temperature: 100 °C
Reaction time: 6 h

Procedure:
To a stirred solution of rac (2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-amino-propyl)-amide (100 mg) in DMF (3 mL), sulfamide (Aldrich, 62 mg) and potassium carbonate (50 mg) were added and the mixture was stirred at 100° C. for 6 hrs. The solvent was removed under reduced pressure and the residue was portioned between EtOAc and water. The organic layer was separated and dried with sodium sulfate. The solvent was removed and the residue was chromatographed on an ISCO machine (70-100% EtOAc/Hexanes) to give a white solid. 25 mg.
Reaction SMILES: [Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][CH:20](SC)[NH:19][C:18]4=[O:24])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.[CH3:31][NH:32][CH2:33][C:34]1([CH2:37][OH:38])[CH2:36][CH2:35]1>>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:32]([CH2:33][C:34]5([CH2:37][OH:38])[CH2:36][CH2:35]5)[CH3:31])=[N:19][C:18]4=[O:24])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:27]([F:28])([F:29])[F:30])[CH:3]=1
Reactant: CSC1NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1
Reactant: CNCC1(CO)CC1
Product: CN(CC1(CO)CC1)C1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1

Procedure:
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[(1-hydroxymethyl-cyclopropylmethyl)-methyl-amino]-thiazol-4-one was prepared from 5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazolidin-4-one and (1-methylaminomethyl-cyclopropyl)-methanol following General Procedure B.
Reaction SMILES: [CH2:1]([NH:5][CH2:6][CH2:7][NH2:8])[CH2:2][CH2:3][CH3:4].C(O[C:12](=[O:18])[C:13]([O:15]CC)=O)C>C(O)(C)C>[CH2:1]([N:5]1[CH2:6][CH2:7][NH:8][C:12](=[O:18])[C:13]1=[O:15])[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(=O)C(=O)OCC
Reactant: CCCCNCCN
Solvent: CC(C)O
Product: CCCCN1CCNC(=O)C1=O
Temperature: 25 °C
Yield: 44 %

Procedure:
To a solution of N-butylethylenediamine (4.78 ml, 34.4 mmol) in isopropanol (60 ml) at 0° C. under a nitrogen atmosphere was added diethyloxalate (4.67 ml, 34.4 mmol). The reaction was allowed to warm to rt and heated to reflux for 6 h. The reaction was concentrated in vacuo and purified via flash chromatography (silica) to yield 1-butylpiperazine-2,3-dione (44%).
Reaction SMILES: C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[NH:26][N:25]=[N:24][N:23]=3)[CH:17]=2)[CH2:10][C@H:9]1[C:28]([N:30]1[CH2:34][CH2:33][S:32][CH2:31]1)=[O:29])=O)(C)(C)C.Cl.O1CCOCC1>CO>[NH:26]1[C:22]([C:18]2[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=2)[C:15]([NH:14][CH2:13][C@H:11]2[CH2:10][C@@H:9]([C:28]([N:30]3[CH2:34][CH2:33][S:32][CH2:31]3)=[O:29])[NH:8][CH2:12]2)=[O:27])=[N:23][N:24]=[N:25]1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](CNC(=O)c2cccc(-c3nnn[nH]3)c2)C[C@H]1C(=O)N1CCSC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: O=C(NC[C@@H]1CN[C@H](C(=O)N2CCSC2)C1)c1cccc(-c2nnn[nH]2)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of Example 30B (292.8 mg, 0.6 mmol) dissolved in methanol (10 mL) was added a solution of 4N HCl in dioxane (1.5 mL, 4 M, 6 mmol) via syringe at room temperature. The mixture was allowed to stir for 12 hours at room temperature, concentrated under reduced pressure to provide the titled compound. MS (ESI) m/e 388 (M+H)+, 386 (M−H)−; 1H NMR (500 MHz, CD3OD) δ ppm 1.97 (m, 1H) 2.86 (m, 2H) 3.16 (m, 2H) 3.39 (m, 1H) 3.61 (s, 2H) 3.69 (m, 1H) 3.76 (s, 2H) 3.97 (m, 1H) 4.53 (m, 2H) 7.69 (m, 1H) 8.07 (m, 1H) 8.20 (m, 1H) 8.57 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]4[NH:22][CH:23]=[C:24]([C:26]([O:28]C)=O)[N:25]=4)=[CH:16][CH:15]=3)[C:10]([CH2:30][CH3:31])=[C:9]([CH3:32])[N:8]=2)=[CH:4][CH:3]=1.[NH3:33]>C(O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]4[NH:22][CH:23]=[C:24]([C:26]([NH2:33])=[O:28])[N:25]=4)=[CH:16][CH:15]=3)[C:10]([CH2:30][CH3:31])=[C:9]([CH3:32])[N:8]=2)=[CH:4][CH:3]=1
Reactant: N
Reactant: CCc1c(C)nc(-c2ccc(Cl)s2)nc1Nc1ccc(Cc2nc(C(=O)OC)c[nH]2)cc1
Solvent: CCO
Product: CCc1c(C)nc(-c2ccc(Cl)s2)nc1Nc1ccc(Cc2nc(C(N)=O)c[nH]2)cc1
Temperature: 25 °C
Yield: 32 %

Procedure:
A 25-mL round bottomed flask was charged with methyl 2-[[4-[[2-(5-chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]phenyl]methyl]-1H-imidazole-4-carboxylate (18 mg, 0.038 mmol) and 2N NH3 in ethanol (10 ml). The mixture was stirred under reflux overnight. After cooling to room temperature, the volatile material was removed under reduced pressure and the residue was purified by chromatography on silica gel using 10% acetone in dichloromethane as eluent to afford the title compound (5.5 mg, 32% yield). MW=452.96. 1H NMR (400 MHz, CDCl3) δ 7.68˜7.65 (m, 4H), 7.30 (d, J=8.0 Hz, 2H), 6.93 (d, J=4.0 Hz, 1H), 6.54 (brs, 1H), 4.45 (brs, 2H), 4.19 (s, 2H), 2.65 (q, J=7.6 Hz, 2H), 2.49 (s, 3H), 1.26 (t, J=7.6 Hz, 3H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[C:32]3[C:27](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=3)[CH2:26][N:25]([CH3:35])[CH2:24]2)[CH:18]=1)(=[O:16])=[O:15].[CH3:36][C:37]([CH3:58])([C:48]([O:50]N1C(=O)CCC1=O)=O)[C:38]([O:40]N1C(=O)CCC1=O)=O>>[Cl:33][C:30]1[CH:31]=[C:32]2[C:27](=[C:28]([Cl:34])[CH:29]=1)[CH2:26][N:25]([CH3:35])[CH2:24][CH:23]2[C:19]1[CH:18]=[C:17]([S:14]([NH:13][CH2:12][CH2:11][O:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][C:48](=[O:50])[C:37]([CH3:36])([CH3:58])[C:38]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]3[C:32]4[C:27](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=4)[CH2:26][N:25]([CH3:35])[CH2:24]3)[CH:18]=2)(=[O:16])=[O:15])=[O:40])(=[O:16])=[O:15])[CH:22]=[CH:21][CH:20]=1
Reactant: CC(C)(C(=O)ON1C(=O)CCC1=O)C(=O)ON1C(=O)CCC1=O
Reactant: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCN)c2)C1
Product: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCNC(=O)C(C)(C)C(=O)NCCOCCOCCOCCNS(=O)(=O)c3cccc(C4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)c2)C1

Procedure:
Compound 182 was prepared from compound 28 and bis(2,5-dioxopyrrolidin-1-yl) 2,2-dimethylmalonate (prepared using the methods outlined in example 168) following the procedure outlined in example 175. The crude product (250 mg) was purified by Prep-HPLC with the following conditions: Column, C18 silica gel; mobile phase, MeCN/H2O/CF3COOH=39/100/0.05; Detector, UV 254 nm. This resulted in 152.3 mg (47%) of a TFA salt of N1,N3-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,2-dimethylmalonamide as a white solid. 1H-NMR (300 MHz, CDCl3, ppm): δ 7.92˜7.89 (d, J=8.1 Hz, 2H), 7.79 (s, 2H), 7.6˜97.64 (m, 2H), 7.57˜7.55 (d, J=7.5 Hz, 4H), 3.68 (s, 2H), 4.87˜4.75 (m, 4H), 4.5˜44.49 (m, 2H), 3.90˜3.88 (m, 2H), 3.67˜3.45 (m, 20H), 3.3˜93.32 (m, 4H), 3.31 (s, 6H), 3.17˜3.05 (m, 4H), 1.41 (s, 1H). MS (m/z): 1189 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:3]=12.[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[CH2:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1.C1(C)C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[CH2:29][N:30]1[CH:34]=[C:33]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:3]=23)[CH:32]=[N:31]1
Reactant: CC1(C)OB(c2cnn(Cc3ccc4ccccc4c3)c2)OC1(C)C
Reactant: C[Si](C)(C)CCOCn1ccc2c(Br)ccnc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(Cc4ccc5ccccc5c4)c3)ccnc21
Temperature: 120 °C
Yield: 88 %

Procedure:
4-Bromo-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (0.06 g, 0.0002 mol) and 1-(2-naphthylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.074 g, 0.00022 mol) were combined in toluene (2.0 mL, 0.019 mol) and ethanol (1.0 mL, 0.017 mol), and then potassium carbonate (0.063 g, 0.00046 mol, in 1 mL water) was added. The reaction mixture was degassed with nitrogen, then tetrakis(triphenylphosphine)palladium(0) (0.02 g, 0.00002 mol) was added, sealed in a tube and heated to 120° C. in a microwave for 30 minutes. This was allowed to cool and then partitioned between ethyl acetate and brine. The organic layer was dried over magnesium sulfate and concentrated to give 4-[1-(2-naphthylmethyl)-1H-pyrazol-4-yl]-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine 0.08 g, as an oily residue, LC/MS (M+H)+: 455.
Reaction SMILES: [CH2:1]([CH2:8][NH:9][C:10]1[CH:11]=[C:12]([CH:14]=[CH:15][C:16]=1[N+:17]([O-:19])=[O:18])[NH2:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:21]([O:23][CH3:24])=[O:22]>C(COC)OC.N1C=CC=CC=1>[CH2:1]([CH2:8][NH:9][C:10]1[CH:11]=[C:12]([NH:13][C:21](=[O:22])[O:23][CH3:24])[CH:14]=[CH:15][C:16]=1[N+:17]([O-:19])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)Cl
Reactant: Nc1ccc([N+](=O)[O-])c(NCCc2ccccc2)c1
Solvent: COCCOC
Solvent: c1ccncc1
Product: COC(=O)Nc1ccc([N+](=O)[O-])c(NCCc2ccccc2)c1
Temperature: 20 °C
Yield: 84 %

Procedure:
A stirred solution of 3-(N-benzylmethylamino)-4-nitroaniline (2.2 g, 8.5 mM) in dry dimethoxyethane (15 ml) and pyridine (4 ml) was treated dropwise with methyl chloroformate (10 mM) at 0° C. The mixture was allowed to warm slowly to 20° C. and after 3 h was quenched with water (5 ml). Volatile solvents were removed under vacuum and the residue was extracted with ethyl acetate. After successive washings with aqueous methanesulfonic acid, water, aqueous KHCO3 and brine the organic layer was dried over Na2SO4. Removal of the solvent and chromatography of the residue on silica gel in ethyl acetate-petroleum ether (3:7) gave the product as a bright red oil (2.25 g, 84% yield).
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3](=[O:20])[CH2:4][C:5]([CH3:19])([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2([CH3:18])[O:17][CH2:16][CH2:15][O:14]2)[CH:8]=1)[CH3:6].[Na].[I-].[CH3:25][S+](C)(C)=O>CS(C)=O>[CH3:19][C:5]([C:7]1[CH:8]=[C:9]([C:13]2([CH3:18])[O:14][CH2:15][CH2:16][O:17]2)[CH:10]=[CH:11][CH:12]=1)([CH3:6])[CH2:4][C:3]1([C:2]([F:1])([F:21])[F:22])[CH2:25][O:20]1
Reactant: C[S+](C)(C)=O
Reactant: CC(C)(CC(=O)C(F)(F)F)c1cccc(C2(C)OCCO2)c1
Agent: [I-]
Agent: [Na]
Solvent: CS(C)=O
Product: CC(C)(CC1(C(F)(F)F)CO1)c1cccc(C2(C)OCCO2)c1
Reaction time: 2 h

Procedure:
To a solution of 1,1,1-trifluoro-4-methyl-4-[3-(2-methyl-[1,3]dioxolan-2-yl)phenyl]pentan-2-one (0.56 g, 1.8 mmol) in anhydrous DMSO (2.3 mL) was added the sodium ylide of trimethylsulfoxonium iodide (2.6 mL of a 0.8M solution in DMSO) over 5 minutes. The mixture was stirred 2 hours, quenched with water, and extracted with ethyl acetate. The combined organic layers were washed with water and brine, and dried over sodium sulfate. The solution was concentrated in vacuo to afford the yellow oil, 2-{3-[1,1-dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]phenyl}-2-methyl-[1,3]dioxolane, which was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:9])[NH:5][CH:6]=[CH:7][CH:8]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][CH2:18][CH2:19][CH2:20][Cl:21]>CN(C)C=O>[Cl:21][CH2:20][CH2:19][CH2:18][CH2:17][N:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[C:4]1=[O:9]
Reactant: COc1ccc[nH]c1=O
Reactant: ClCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cccn(CCCCCl)c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 42 %

Procedure:
A mixture of 3-methoxy-2(1H)-pyridone (0.54 g, 4.31 mmol) and potassium carbonate (0.71 g, 5.14 mmol) in anhydrous N,N-dimethylformamide (20 mL) was stirred at room temperature for 1 h. 1-Bromo-4-chlorobutane (0.50 mL, 4.33 mmol) was then added and the resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with water (20 mL) and extracted with dichloromethane (3×30 mL). The organic layers were collected, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel, eluting with 100% dichloromethane and 5% methanol in dichloromethane to afford the title compound as a pale yellow oil (0.39 g, 42%). 1H NMR (400 MHz, CDCl3) δ ppm 6.87 (dd, 1H) 6.59 (dd, 1H) 6.10 (t, 1H) 4.02 (t, 2H) 3.81 (s, 3H) 3.57 (t, 2H) 2.01-1.87 (m, 2H) 1.87-1.73 (m, 2H).
Reaction SMILES: [CH3:1][Si:2]([CH3:38])([CH3:37])[CH2:3][CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[S:16][C:17]3[CH:23]=[C:22]([C:24]4[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH:25]=4)[CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7]>C(OCC)(=O)C.[Pd]>[CH3:1][Si:2]([CH3:37])([CH3:38])[CH2:3][CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[S:16][C:17]3[CH:23]=[C:22]([CH:24]4[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:26][CH2:25]4)[CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7]
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc3nc(OC4CCN(C(=O)OCC[Si](C)(C)C)CC4)sc3c2)CC1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(c2ccc3nc(OC4CCN(C(=O)OCC[Si](C)(C)C)CC4)sc3c2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.1 %

Procedure:
To a solution of tert-butyl 4-(2-(1-((2-(trimethylsilyl)ethoxy)carbonyl)-piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (555 mg, 0.991 mmol) in ethyl acetate (10 mL) was added Pd/C (10%, 2.638 g, 2.48 mmol). The mixture was charged with a balloon of H2 and stirred at rt overnight. The reaction mixture was filtered through a pad of celite and rinsed with EtOAc. The filtrate was concentrated to afford tert-butyl 4-(2-(1-((2-(trimethylsilyl)ethoxy)carbonyl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)piperidine-1-carboxylate (385 mg, 0.685 mmol, 69% yield) as a gray gum. LCMS (m/z)=562 (M+H)+.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[CH2:6]1[O:14][CH:7]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CCO.N1C=CC=CC=1>[N:1]1([CH2:6][CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[OH:14])[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: c1ccc(C2CO2)cc1
Reactant: c1c[nH]cn1
Solvent: c1ccncc1
Solvent: CCO
Product: OC(Cn1ccnc1)c1ccccc1
Yield: 35.2 %

Procedure:
A solution of 17.6 g (0.258 mol) of imidazole in 100 mL of absolute EtOH was treated with 0.6 mL (4.0 mmol) of pyridine and refluxed for 25 minutes. This was then treated dropwise with a solution of 31.06 g (0.258 mol) of styrene oxide and the solution heated at reflux overnight. The solvent was removed under reduced pressure and the residue taken up in Et2O and washed with H2O. A solid separated which was collected and dissolved in warm CHCl3 /EtOAc. The organic phase was washed with saturated NaCl and dried over MgSO4. Treatment of the filtrate with charcoal, filtering, and concentrating to 1/3 volume caused a solid to separate. There was collected 17.09 g (35% yield) of the product as a white solid, mp 146-148° C. The structure was confirmed by NMR and mass spectroscopy. MS m/z 189 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)=[CH:4][C:3]=1[O:16][CH3:17].Cl[CH2:19][C:20]1[N:21]=[C:22](/[CH:25]=[CH:26]/[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:23][CH:24]=1>>[CH3:17][O:16][C:3]1[CH:4]=[C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:6]=[CH:7][C:2]=1[O:1][CH2:19][C:20]1[N:21]=[C:22](/[CH:25]=[CH:26]/[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:23][CH:24]=1
Reactant: COc1cc(CCCn2cncn2)ccc1O
Reactant: ClCc1coc(/C=C/c2ccccc2)n1
Product: COc1cc(CCCn2cncn2)ccc1OCc1coc(/C=C/c2ccccc2)n1
Yield: 62 %

Procedure:
In substantially the same manner as in Working Example 37, 1-[3-(4-hydroxy-3-methoxyphenyl)propyl]-1,2,4-triazole was allowed to react with 4-chloromethyl-2-[(E)-2-phenylethenyl]oxazole to give 1-[3-[3-methoxy-4-[2-[(E)-2-phenylethenyl]-4-oxazolylmethoxy]phenyl]propyl]-1,2,4-triazole. The yield was 62%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 113-114° C.