Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([CH3:19])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[C:20]1([C@@H:26]([CH3:30])[C:27](O)=[O:28])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH3:19][N:12]1[C:13]2[N:14]=[CH:15][N:16]=[CH:17][C:18]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:27](=[O:28])[C@@H:26]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:30])[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1
Reactant: Cn1cc(C(=O)c2cncc(N)c2)c2cncnc21
Reactant: C[C@@H](C(=O)O)c1ccccc1
Product: C[C@@H](C(=O)Nc1cncc(C(=O)c2cn(C)c3ncncc23)c1)c1ccccc1

Procedure:
The title compound was prepared according to the method described for Library protocol 1 starting from (5-amino-pyridin-3-yl)-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone (Preparation 110) and (2R)-2-phenylpropanoic acid to afford the title compound. LCMS: Rt=2.52 min; m/z 386 [M+H]+.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[C:15]([CH3:22])[CH:14]=2)[CH2:9]1>CO.C(Cl)Cl.[Pd]>[CH3:22][C:15]1[CH:14]=[C:13]([N:10]2[CH2:11][CH2:12][C@H:8]([CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][C@@H:2]3[CH3:1])[CH2:9]2)[CH:18]=[CH:17][C:16]=1[NH2:19]
Reactant: Cc1cc(N2CC[C@H](CN3CCC[C@@H]3C)C2)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Solvent: ClCCl
Product: Cc1cc(N2CC[C@H](CN3CCC[C@@H]3C)C2)ccc1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of (2S,3R)-2-methyl-1-[1-(3-methyl-4-nitro-phenyl)-pyrrolidin-3-yl-methyl]-pyrrolidine (0.3 g, 1 mmol) in MeOH (15 mL) was deaerated and nitrogen was introduced. To this solution was added Pd—C (10%, 30 mg). This mixture was stirred under H2 atmosphere at r.t. overnight. TLC (10% MeOH in DCM) and LC/MS showed the reaction was complete, product peak was observed at t=1.458 min, m/z: 274 (M). The mixture was passed through a Celite pad, rinsed with methanol. The filtrate was concentrated to dryness, and further dried under high vacuum to yield the title compound as a reddish brown liquid after drying under high vacuum.
Reaction SMILES: [H-].[Li+:2].[C:3]([C:5]([C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[C:6]([OH:17])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15])#[N:4].C1COCC1>CCOCC>[Li+:2].[C:3]([C:5]([C:18](=[O:23])[C:19]([CH3:21])([CH3:20])[CH3:22])=[C:6]([O-:17])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[N+:14]([O-:16])=[O:15])#[N:4]
Reactant: CC(C)(C)C(=O)C(C#N)=C(O)c1ccc(Cl)cc1[N+](=O)[O-]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(C)C(=O)C(C#N)=C([O-])c1ccc(Cl)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 81.8 %

Procedure:
To a stirred slurry of 0.36 g of LiH in 15 ml of dry ether under N2 at room temperature was rapidly added a solution of 1.5 g of 2-cyano-4,4-dimethyl-1-hydroxy-3-oxo-1-(2-nitro-4-chlorophenyl)-1-pentene dissolved in 15 ml of dry ether. The reaction mixture turned brown and a precipitate formed with 5 min. Enough dry THF was added to dissolve the solid and the mixture allowed to stir overnight at ambient temperature. The reaction was filtered and the filtrate concentrated under reduced pressure to yield 1.25 g of product as a yellow solid, m.p. >230° C. (decomp.).
Reaction SMILES: [CH3:1][N:2]1[C:9]([NH:10][OH:11])=[CH:8][C:6](=[O:7])[N:5]([CH3:12])[C:3]1=[O:4].[CH:13]([O-])([O-])OCC>CN(C)C=O>[CH3:12][N:5]1[C:6](=[O:7])[C:8]2=[CH:13][O:11][N:10]=[C:9]2[N:2]([CH3:1])[C:3]1=[O:4]
Reactant: Cn1c(NO)cc(=O)n(C)c1=O
Reactant: CCOC([O-])[O-]
Solvent: CN(C)C=O
Product: Cn1c(=O)c2conc2n(C)c1=O

Procedure:
A mixture of 2 g of 1,3-dimethyl-6-hydroxyamino-uracil, 20 ml of dimethylformamide and 20 ml of ethyl orthoformate is boiled at 160° C. for 1 hour, after which the solvent is distilled off. To the residue is added ethanol and the resultant crystals are collected by filtration. As recrystallized from hot water, 1.0 g of the captioned compound is obtained as colorless prisms, melting point: 170°-171° C.
Reaction SMILES: C([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:20]([CH3:21])[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[N:13]=1)C1C=CC=CC=1.C(O)=O>CO.[OH-].[OH-].[Pd+2]>[CH3:21][N:20]1[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[N:13]=[C:12]1[CH2:11][CH2:10][CH2:9][OH:8]
Reactant: Cn1c(CCCOCc2ccccc2)nc2cccnc21
Agent: [Pd+2]
Agent: [OH-]
Solvent: O=CO
Solvent: CO
Product: Cn1c(CCCO)nc2cccnc21
Temperature: 25 °C
Yield: 81.7 %

Procedure:
A mixture of 2-[3-(benzyloxy)propyl]-3-methyl-3H-imidazo[4,5-b]pyridine (1.8 g), 20% palladium hydroxide on carbon (2.35 g, containing water (50%)), and formic acid (8.45 mL) in methanol (84.5 mL) was refluxed for 6 hr. The mixture was allowed to cool to room temperature, and the catalyst was filtered off. The obtained filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.0 g).
Reaction SMILES: [C:1]([OH:5])(=O)[CH2:2][CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:30][C:31]1[CH:32]=[C:33]([NH:37][C:38]2[CH:43]=[C:42]([NH:44][C:45]3[CH:50]=[CH:49][C:48]([O:51][C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)=[CH:47][CH:46]=3)[N:41]=[CH:40][N:39]=2)[CH:34]=[CH:35][CH:36]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[O:51]([C:48]1[CH:47]=[CH:46][C:45]([NH:44][C:42]2[N:41]=[CH:40][N:39]=[C:38]([NH:37][C:33]3[CH:32]=[C:31]([NH:30][C:1](=[O:5])[CH2:2][CH3:3])[CH:36]=[CH:35][CH:34]=3)[CH:43]=2)=[CH:50][CH:49]=1)[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1
Reactant: CCC(=O)O
Reactant: Nc1cccc(Nc2cc(Nc3ccc(Oc4ccccc4)cc3)ncn2)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCC(=O)Nc1cccc(Nc2cc(Nc3ccc(Oc4ccccc4)cc3)ncn2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of propionic acid (12 mg, 0.1 mmol) in DMF (0.6 mL) was added HATU (92 mg, 0.2 mmol) and the reaction mixture was stirred at room temperature for 30 min. To it was added N4-(3-aminophenyl)-N6-(4-phenoxyphenyl)pyrimidine-4,6-diamine (60 mg, 0.1 mmol) followed by DIPEA (41 mg, 0.3 mmol) and the reaction mixture was stirred at this temperature for 16 h. It was concentrated under reduced pressure. The residue was diluted with CH2Cl2 (5 mL) and was washed with NaHCO3 solution (2 mL), water (2 mL), and brine (2 mL). Drying over Na2SO4 followed by concentration under reduced pressure offered a residue that was purified by column chromatography (SiO2, 230-400, chloroform/methanol:9/1) to give N-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)propionamide (IR-10) as a brown solid. 1H NMR (DMSO-d6) δ ppm: 1.06 (t, J=7.56 Hz, 3H), 2.30 (q, J=7.48 Hz, 2H), 6.13 (s, 1H), 6.94-6.99 (m, 4H), 7.08 (t, J=7.36 Hz, 1H), 7.16-7.24 (m, 3H), 7.36 (t, J=7.44 Hz, 2H), 7.54 (d, J=8.88 Hz, 2H), 7.81 (s, 1H), 8.23 (s, 1H), 9.12 (s, 2H), 9.81 (s, 1H); LCMS: m/e 426.3 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15]N)=[CH:11][CH:10]=2)=[O:7])=[CH:4][CH:3]=1.[C:19]1(=[O:35])[N:23]([CH2:24][CH2:25][CH2:26][C:27](=O)[CH3:28])[C:22](=[O:30])[C:21]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:20]12.Cl.CCCCCC>C(O)C>[CH3:28][C:27]1[NH:15][C:12]2[C:13]([C:26]=1[CH2:25][CH2:24][N:23]1[C:22](=[O:30])[C:21]3=[CH:31][CH:32]=[CH:33][CH:34]=[C:20]3[C:19]1=[O:35])=[CH:14][C:9]([NH:8][C:6](=[O:7])[C:5]1[CH:17]=[CH:18][C:2]([F:1])=[CH:3][CH:4]=1)=[CH:10][CH:11]=2
Reactant: NNc1ccc(NC(=O)c2ccc(F)cc2)cc1
Reactant: CC(=O)CCCN1C(=O)c2ccccc2C1=O
Agent: Cl
Solvent: CCCCCC
Solvent: CCO
Product: Cc1[nH]c2ccc(NC(=O)c3ccc(F)cc3)cc2c1CCN1C(=O)c2ccccc2C1=O
Temperature: 80 °C
Reaction time: 6 h
Yield: 6.6 %

Procedure:
To a solution of 5.33 gm (21.7 mMol) 4-(4-fluorobenzoyl)aminophenylhydrazine and 5.03 gm (21.8 mMol) 5-phthalimidyl-2-pentanone in 100 mL ethanol were added 2 mL concentrated hydrochloric acid and the reaction mixture was heated at 80° C. for 14 hours. To the reaction mixture were then added an additional 3 mL concentrated hydrochloric acid and heating continued for an additional 6 hours. The reaction mixture was then cooled to 0° C. and 100 mL hexane were slowly added. The solid which formed was filtered and washed with hexane and provided, after drying, 6.67 gm of the desired compound. The mother liquor was concentrated under reduced pressure and then subjected to silica gel chromatography, eluting with 1:1 hexane:ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide an additional 0.63 gm of product. Overall yield was 7.3 gm (76%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:36]=[CH:35][CH:34]=[CH:33][C:9]=1[C:10]([NH:12][C:13]1[CH:32]=[CH:31][C:16]([C:17]([N:19]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[C:23](=[O:30])[CH2:22][CH2:21][CH2:20]2)=[O:18])=[CH:15][CH:14]=1)=[O:11].[BH4-].[Na+]>CO.C(Cl)(Cl)Cl>[OH:30][CH:23]1[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[N:19]([C:17](=[O:18])[C:16]2[CH:15]=[CH:14][C:13]([NH:12][C:10](=[O:11])[C:9]3[CH:33]=[CH:34][CH:35]=[CH:36][C:8]=3[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[CH3:1])=[CH:32][CH:31]=2)[CH2:20][CH2:21][CH2:22]1
Reactant: Cc1ccccc1-c1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(=O)c3ccccc32)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: Cc1ccccc1-c1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(O)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 93.2 %

Procedure:
To a solution of 1-{4-[2-(2-methylphenyl)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (620 mg) in methanol (20 ml) was added sodium borohydride (49.4 mg) and the mixture was stirred at ambient temperature for 4 hours. The mixture was diluted with chloroform and the solution was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated in vacuo to give a syrup and the residue was purified by silica gel column (30g, 1% methanol in chloroform) to give 5-hydroxy-1-{4-[2-(2-methylphenyl)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-1-benzazepine (580 mg).
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][C@H:12]([CH3:17])[CH2:11]3)[C:4]([CH3:7])=[CH:5][CH:6]=1.C(=O)(O)[O-].[Na+].Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C1COCC1.O>[CH3:1][C:2]1[N:3]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[C@H:12]([CH3:17])[CH2:11]3)[C:4]([CH3:7])=[CH:5][CH:6]=1
Reactant: Cc1ccc(C)n1-c1ccc2c(c1)C[C@@H](C)N2
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(C)n1-c1ccc2c(c1)C[C@@H](C)N2C(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a stirred solution of (2R)-5-(2,5-dimethyl-1H-pyrrol-1yl)-2,3-dihydro-2-methyl-1H-indole (Step 2, 0.100 g, 0.442 mmol) in THF/H2O (8:1, 4.5 mL) is added sodium bicarbonate (0.072 g, 0.884 mmol) followed by benzyl chloroformate (80 μL, 0.53 mmol) at 0° C. The reaction mixture is stirred at 0° C. for 30 mins and at ambient temperature for 2 h and is then concentrated under reduced pressure. The residue is taken up in CH2Cl2 (40 mL), washed with H2O (2×10 mL) and saline (2×10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified by chromatography on a Biotage Flash 40S 40 g silica gel cartridge (1% EtOAc/Hexanes) to give the title compound, MS (ESI+) for C23H24N2O2 m/z 361 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[C:17]([Cl:24])[C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([O:15][CH3:16])=[C:9]([S:11](Cl)(=[O:13])=[O:12])[CH:10]=1.C(N(CC)CC)C.[CH:32]1([NH2:36])[CH2:35][CH2:34][CH2:33]1>C(Cl)Cl>[CH:32]1([NH:36][S:11]([C:9]2[CH:10]=[C:5]([O:4][C:3]3[C:2]([Cl:1])=[CH:20][C:19]([N+:21]([O-:23])=[O:22])=[CH:18][C:17]=3[Cl:24])[CH:6]=[CH:7][C:8]=2[O:15][CH3:16])(=[O:13])=[O:12])[CH2:35][CH2:34][CH2:33]1
Reactant: NC1CCC1
Reactant: COc1ccc(Oc2c(Cl)cc([N+](=O)[O-])cc2Cl)cc1S(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(Oc2c(Cl)cc([N+](=O)[O-])cc2Cl)cc1S(=O)(=O)NC1CCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 37.1 %

Procedure:
To a solution of 5-(2,6-Dichloro-4-nitro-phenoxy)-2-methoxy-benzenesulfonyl chloride (1.3 grams, 3.2 mmol) in methylene chloride (30 mL) at 0° C. was added triethylamine (0.58 mL, 4.1 mmol) followed by cyclobutylamine (0.27 mL, 3.2 mmol). After stirring at room temperature for 2 hours, the reaction mixture was quenched with 1N hydrochloric acid (25 mL) and extracted with methylene chloride (3 times 15 mL). The combined organic extracts were washed with 1N HCl (20 mL), saturated aqueous NaHCO3 (2 times 20 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (30% ethyl acetate in hexane) to afford the title compound (531 mg). 1H NMR (400 MHz, CDCl3) δ8.28 (s, 2H), 7.28 (d, 1H), 7.07-7.04 (dd, 1H), 6.98 (d, 1H), 5.26 (d, 1H), 3.96 (s, 3H), 3.71-3.69 (m, 1H), 1.99-1.92 (m, 2H), 1.74-1.68 (m, 2H), 1.57-1.48 (m, 2H). MS (APCI−) Calc: 446.1, Found: 445.2 (M−1).
Reaction SMILES: [Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:21]([C:23](O)=[O:24])[N:22]=2)[CH2:14][C@H:13]1[O:31][CH3:32])=[O:10].[CH3:33][NH:34][CH3:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>O>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:21]([C:23]([N:34]([CH3:35])[CH3:33])=[O:24])[N:22]=2)[CH2:14][C@H:13]1[O:31][CH3:32])=[O:10]
Reactant: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3[nH]c(C)c(Cl)c3Cl)[C@H](OC)C2)nc1C(=O)O
Reactant: CNC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3[nH]c(C)c(Cl)c3Cl)[C@H](OC)C2)nc1C(=O)N(C)C

Procedure:
A solution of Cis(±)-2-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-5-(ethoxycarbonyl)-1,3-thiazole-4-carboxylic acid (0.062 g, 0.12 mmol, Example 188), dimethylamine (0.06 mL, 2M solution in THF, Aldrich), HATU (0.05 g, 0.13 mmol) and triethylamine (0.018 mL, 0.13 mmol) was stirred at room temperature until complete by LCMS (about 30 min). The crude reaction mixture was slowly poured into water and the resulting white precipitate was filtered, washed with water and dried under vacuum to yield pure product (0.028 g). MS (ES) MH+: 532 for C21H27Cl2N5O5S; NMR: 1.20 (t, 3 H) 1.76 (s, 2 H) 2.18 (s, 3 H) 2.78 (s, 3 H) 2.93 (s, 3 H) 3.29 (d, 1 H) 3.36 (s, 3 H) 3.39-3.43 (m, 1 H) 3.55 (s, 1 H) 3.91 (s, 1 H) 4.15 (q, 2 H) 4.29 (s, 2 H) 7.15 (d, 1 H) 12.14 (s, 1 H).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:29]=[CH:28][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][C:15]([CH:19]=[C:20]4[S:24][C:23](SC)=[N:22][C:21]4=[O:27])=[CH:16][CH:17]=3)[CH:12]=[N:11]2)=[C:7]([C:30]([F:33])([F:32])[F:31])[CH:6]=1)(=[O:4])=[O:3].[N:34]1([CH2:40][CH2:41][OH:42])[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>>[OH:42][CH2:41][CH2:40][N:34]1[CH2:39][CH2:38][N:37]([C:23]2[S:24][C:20](=[CH:19][C:15]3[CH:14]=[C:13]4[C:18](=[CH:17][CH:16]=3)[N:10]([CH2:9][C:8]3[CH:28]=[CH:29][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:6][C:7]=3[C:30]([F:33])([F:31])[F:32])[N:11]=[CH:12]4)[C:21](=[O:27])[N:22]=2)[CH2:36][CH2:35]1
Reactant: OCCN1CCNCC1
Reactant: CSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(S(C)(=O)=O)cc3C(F)(F)F)c2)S1
Product: CS(=O)(=O)c1ccc(Cn2ncc3cc(C=C4SC(N5CCN(CCO)CC5)=NC4=O)ccc32)c(C(F)(F)F)c1

Procedure:
2-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-5-[1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-thiazol-4-one was prepared from 5-[1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazol-4-one and 2-piperazin-1-yl-ethanol following General Procedure C.
Reaction SMILES: [CH3:1][O:2][CH2:3]Cl.[OH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH3:13])=[CH:8][CH:7]=1.Cl>C(N(C(C)C)CC)(C)C>[CH3:1][O:2][CH2:3][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH3:13])=[CH:8][CH:7]=1
Reactant: COCCl
Reactant: CC(=O)c1ccc(O)cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Product: COCOc1ccc(C(C)=O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
4 ml of chloromethyl methyl ether was added dropwise to a solution of 4′-hydroxyacetophenone (5.44 g) and diisopropylethylamine (10 ml) in 40 ml dinethylformamide at room temperature and stirred at room temperature for 3 hours. After addition of 2 mol/l hydrochloric acid, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate. The drying agent was filtered off and the solvent was evaporated to give a residue, which was then purified via column chromatography on silica gel (hexane:ethyl acetate=7:1) to provide 4′-(methoxymethoxy)acetophenone (6.73 g, 93%) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][NH:11][C@@H:10]([CH3:14])[CH2:9]2)=[C:4]([C:15]([F:18])([F:17])[F:16])[CH:3]=1.[Br:19][C:20]1[CH:21]=[C:22]([S:26](Cl)(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1>>[Br:19][C:20]1[CH:21]=[C:22]([S:26]([N:11]2[CH2:12][CH2:13][C@H:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=3[C:15]([F:18])([F:16])[F:17])[CH2:9][C@@H:10]2[CH3:14])(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1
Reactant: O=S(=O)(Cl)c1cccc(Br)c1
Reactant: C[C@H]1C[C@@H](c2ccc(F)cc2C(F)(F)F)CCN1
Product: C[C@H]1C[C@@H](c2ccc(F)cc2C(F)(F)F)CCN1S(=O)(=O)c1cccc(Br)c1
Yield: 97 %

Procedure:
Prepared from (2S,4S)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperidine (120 mg, 0.46 mmol) and 3-bromophenylsulfonyl chloride (99.4 mL, 0.69 mmol) according to scheme III-11 in 97% yield. HRMS: calcd for C19H18BrF4NO2S+H+, 480.02505. found (ESI-FTMS, [M+H]1+), 480.02396.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([CH2:10][CH2:11][OH:12])=[CH:4][C:3]=1[C:13](=[O:15])[CH3:14].[Br:16]Br>C(Cl)Cl>[Br:16][CH2:14][C:13]([C:3]1[CH:4]=[C:5]([CH2:10][CH2:11][OH:12])[C:6]([O:8][CH3:9])=[CH:7][C:2]=1[OH:1])=[O:15]
Reactant: BrBr
Reactant: COc1cc(O)c(C(C)=O)cc1CCO
Solvent: ClCCl
Product: COc1cc(O)c(C(=O)CBr)cc1CCO
Temperature: 25 °C
Reaction time: 1 h

Procedure:
10.0 g of 1-(2-hydroxy-5-(2-hydroxyethyl)-4-methoxyphenyl)-1-ethanone was dissolved in 100 ml of methylene chloride. Thereafter, 2.94 ml of bromine was added dropwise to the obtained solution. The obtained mixture was stirred at a room temperature for 1 hour. Thereafter, the reaction mixture was poured into ice water, and an organic layer was separated. The organic layer was successively washed with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. The solvent was then distilled away under a reduced pressure, so as to obtain 16.4 g of a yellow oil product, 2-bromo-1-(2-hydroxy-5-(2-hydroxyethyl)-4-methoxyphenyl)-1-ethanone.
Reaction SMILES: [O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][OH:12])[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1>ClCCl.[O-2].[O-2].[Mn+4]>[O:1]1[C:10]2[CH:9]=[C:8]([CH:11]=[O:12])[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: OCc1cc2c(cn1)OCCO2
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: O=Cc1cc2c(cn1)OCCO2
Yield: 60.6 %

Procedure:
A solution of (2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-methanol (250 mg, 1.5 mmol) in dichloromethane (5 mL) was treated with manganese dioxide (650 mg, 7.5 mmol). After 3 days the mixture was filtered and evaporated affording a white solid (150 mg, 61%); MS (APCl+) m/z 166 (MH+).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:19]=[CH:18][C:8]([O:9][C:10]2[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].Cl.[NH2:21][OH:22].Cl>N1C=CC=CC=1>[CH:1]([O:4][C:5]1[CH:19]=[CH:18][C:8]([O:9][C:10]2[CH:17]=[CH:16][C:13]([CH:14]=[N:21][OH:22])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Oc1ccc(Oc2ccc(C=O)cc2)cc1
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: CC(C)Oc1ccc(Oc2ccc(C=NO)cc2)cc1
Yield: 98.1 %

Procedure:
To a solution of Example 17B (1.42 g, 5.56 mmol) in pyridine (10 mL) was added hydroxylamine hydrochloride (3.30 g, 47.5 mmol). The mixture was heated to reflux with a heat gun. After cooling, the mixture was poured into 10% HCl. The precipitates were collected and washed with 10% HCl followed by water, and then dried under vacuum at 50° C. overnight to give the desired product as a white solid (1.48 g, 98%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[C:10]([Si:14](Cl)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:13])([CH3:12])[CH3:11].N1C=CN=C1.CN(C)C=O>O>[Si:14]([O:6][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([Br:1])[CH:3]=1)([C:10]([CH3:13])([CH3:12])[CH3:11])([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: OCc1cccc(Br)c1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](OCc1cccc(Br)c1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.6 %

Procedure:
A mixture of 3-bromobenzyl alcohol (15.0 g, 80 mmol), tert-butylchlorodiphenylsilane (22.9 mL, 88 mmol), imidazole (12.0 g, 176 mmol) and 75 mL of dimethylformamide was stirred at room temperature overnight. The reaction mixture was poured into cold water, extracted with diethyl ether, the extracts washed with water and brine, dried over sodium sulfate and evaporated. The resulting oil was purified by chromatography on silica gel with hexane to give 23.7 g (70%) of 3-bromobenzyl tert-butyldiphenylsilyl ether as a colorless oil.
Reaction SMILES: [CH3:1][N:2]=[C:3]=[O:4].[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([N:16]([CH3:28])[CH2:17][C:18]2[N:19]([CH3:27])[C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:15])=[CH:8][CH:7]=1.C(N(CC)CC)C>CN(C=O)C>[CH3:28][N:16]([CH2:17][C:18]1[N:19]([CH3:27])[C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14](=[O:15])/[CH:13]=[CH:12]/[C:9]1[CH:10]=[N:11][C:6]([NH:5][C:3]([NH:2][CH3:1])=[O:4])=[CH:7][CH:8]=1
Reactant: CN=C=O
Reactant: CN(Cc1cc2ccccc2n1C)C(=O)/C=C/c1ccc(N)nc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CNC(=O)Nc1ccc(/C=C/C(=O)N(C)Cc2cc3ccccc3n2C)cn1
Reaction time: 120 h
Yield: 43.4 %

Procedure:
Methyl isocyanate (0.18 mL, 3.05 mmole) was added to a solution of (E)-3-(6-aminopyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (0.20 g, 0.61 mmole) and triethylamine (0.17 mL, 1.22 mmole) in DMF (20 mL) at RT. The reaction was stirred for 5 days, then was concentrated in vacuo, and the residue was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated. Flash chromatography on silica gel (ethyl acetate) gave the title compound (0.10 g, 43%) as an off white solid: MS (ES) m/e 378 (M+H)+.
Reaction SMILES: [CH3:1][C:2]([O:4][CH2:5][C@H:6]1[O:11][C@@H:10]([O:12]C(C)=O)[C@H:9]([O:16][C:17]([CH3:19])=[O:18])[C@@H:8]([O:20][C:21]([CH3:23])=[O:22])[C@H:7]1[O:24][C:25]([CH3:27])=[O:26])=[O:3].C(N)C1C=CC=CC=1>C1COCC1>[C:17]([O:16][C@@H:9]1[C@@H:8]([O:20][C:21](=[O:22])[CH3:23])[C@@H:7]([O:24][C:25](=[O:26])[CH3:27])[C@@H:6]([CH2:5][O:4][C:2](=[O:3])[CH3:1])[O:11][C@H:10]1[OH:12])(=[O:18])[CH3:19]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Solvent: NCc1ccccc1
Solvent: C1CCOC1
Product: CC(=O)OC[C@H]1O[C@@H](O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
The synthesis of compound 9 is illustrated in FIG. 6. 20 g (51.24 mmol) of β-D-galactosepentaacetate 1 was dissolved in 150 ml THF and 6.7 ml (61.49 mmol) of benzylamine was added with a dropping funnel. The reaction was stirred for 18 h at room temperature to give 2,3,4,6-tetra-O-acetyl-β-D-galactopyranose 2.