Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]3[N:25]=[CH:26][C:27]([C:28](O)=[O:29])=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12].[S:33]([C:37]1[CH:38]=[C:39]([NH2:43])[CH:40]=[CH:41][CH:42]=1)(=[O:36])(=[O:35])[NH2:34]>>[S:33]([C:37]1[CH:38]=[C:39]([NH:43][C:28]([C:27]2[CH:26]=[N:25][N:18]3[C:19]([C:21]([F:22])([F:24])[F:23])=[CH:20][C:15]([C:7]4[CH:8]=[CH:9][C:10]([C:11]([F:14])([F:13])[F:12])=[C:5]([O:4][CH2:3][C:2]([F:32])([F:31])[F:1])[CH:6]=4)=[N:16][C:17]=23)=[O:29])[CH:40]=[CH:41][CH:42]=1)(=[O:35])(=[O:36])[NH2:34]
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)c(OCC(F)(F)F)c3)nc12
Reactant: Nc1cccc(S(N)(=O)=O)c1
Product: NS(=O)(=O)c1cccc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)c(OCC(F)(F)F)c4)nc23)c1

Procedure:
The title compound was prepared from 5-[3-(2,2,2-trifluoroethoxy)-4-trifluoromethyl-phenyl]-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.10) and 3-sulfamoyl-phenylamine [commercially available] according to general procedure II. Yellow solid. MS (ISP) 626.1 [(M−H)−]; mp 233° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=O)[O:5][CH:6]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:7][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[O:5][CH:6]=1
Reactant: O=Cc1cc(Br)co1
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Brc1coc(CN2CCOCC2)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 85.5 %

Procedure:
To a solution of 4-bromofuran-2-carbaldehyde (500 mg, 2.85 mmol) and morpholine (0.5 mL, 5.71 mmol) in CH2Cl2 (10 mL) was added sodium triacetoxyborohydride (1.2 g, 5.71 mmol). The mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with EtOAc (100 mL). The organic phase was washed with aqueous NaHCO3 and brine then dried (MgSO4), filtered and concentrated to dryness. The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2) to afford the sub-title compound (600 mg, 86%).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][CH:16]=1)[C:9]1[N:10]=[C:11]([NH2:13])[S:12][C:8]=1[CH2:7][CH2:6]2>ClCCl>[NH2:13][C:11]1[S:12][C:8]2[CH2:7][CH2:6][C:5]3[C:14](=[CH:15][CH:16]=[C:3]([OH:2])[CH:4]=3)[C:9]=2[N:10]=1
Reactant: COc1ccc2c(c1)CCc1sc(N)nc1-2
Solvent: ClCCl
Product: Nc1nc2c(s1)CCc1cc(O)ccc1-2
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.2 %

Procedure:
To 7-methoxy-4,5-dihydronaphtho[1,2-d]thiazol-2-amine (15 mg, 0.065 mmol) into dichloromethane (2 mL), cooled to 0° C. was added borontribromide (0.258 mL, 0.258 mmol) slowly at 0° C. The reaction mixture was allowed to warm to room temperature and stirred at room temperature overnight. The reaction mixture was quenched by the slow addition of a few drops of MeOH and purified by prep. HPLC (Luna 5 u C18 21.2*100 mm column; 0%-100% 10mins gradient; Solvent A: 10% MeOH-90% H2O-0.1% TFA; Solvent B: 90% MeOH-90% H2O-0.1% TFA). The desired fractions were collected, concentrated and dried under vacuum to provide 13.5 mg of the title compound as a white solid. LC/MS M+1=219.1. The product had an HPLC retention time=1.51 min. (condition A). 1H NMR (400 MHz, CD3OD) δ ppm 7.35 (1H, d, J=8.36 Hz), 6.71-6.83 (2H, m), 3.04 (2H, d, J=8.14 Hz), 2.78-2.90 (2H, m).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.Br[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([S:19][CH3:20])=[C:15]([F:21])[CH:14]=1>COCCOC.[Zn].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>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](=[O:7])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([S:19][CH3:20])=[C:15]([F:21])[CH:14]=2)=[CH:4][CH:3]=1
Reactant: CSc1ccc(CBr)cc1F
Reactant: O=C(Cl)c1ccc(Br)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Zn]
Solvent: COCCOC
Product: CSc1ccc(CC(=O)c2ccc(Br)cc2)cc1F
Reaction time: 2.5 h
Yield: 72.8 %

Procedure:
To the mixture of 4-bromobenzoyl chloride (10.81 g, 49.26 mmol), zinc (4.40 g, 67.24 mmol) and tetrakis(triphenylphosphine)palladium(0) (2.99 g, 2.586 mmol) in DME (250 mL) was added dropwise the solution of 4-(bromomethyl)-2-fluoro-1-(methylsulfanyl)benzene (12.16 g, 51.72 mmol) in DME (120 mL) at room temperature. After 2.5 hour, the mixture was filtered through celite, the filtrate was evaporated, diluted with ethyl acetate (300 mL), washed with water (100 mL), brine (100 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was washed with ethyl acetate-isopropylether, to give the subtitle compound (12.16 g, 73% yield) as a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:6](Cl)=[O:7].[NH2:20][C:21]1[CH:22]=[C:23]([NH:28][C:29](=[O:39])[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([N:36]([CH3:38])[CH3:37])[CH:31]=2)[CH:24]=[CH:25][C:26]=1[CH3:27]>C(Cl)Cl>[CH3:38][N:36]([CH3:37])[C:32]1[CH:31]=[C:30]([CH:35]=[CH:34][CH:33]=1)[C:29]([NH:28][C:23]1[CH:24]=[CH:25][C:26]([CH3:27])=[C:21]([NH:20][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:11]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:22]=1)=[O:39]
Reactant: Cc1ccc(NC(=O)c2cccc(N(C)C)c2)cc1N
Reactant: COc1cc(C(=O)Cl)ccc1OCc1ccccc1
Solvent: ClCCl
Product: COc1cc(C(=O)Nc2cc(NC(=O)c3cccc(N(C)C)c3)ccc2C)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 9 %

Procedure:
A solution of 3-methoxy-4-benzyloxybenzoyl chloride (3.01 g) in methylene chloride (50 ml) was added to a stirred suspension of N-(3-amino-4-methylphenyl)-3-dimethylaminobenzamide (2.69 g) in methylene chloride (30 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The organic phase was washed with water and with a saturated aqueous sodium bicarbonate solution, dried and evaporated. The solid residue was stirred in diethyl ether for 16 hours, filtered and dried to give N-[5-(3-dimethylaminobenzamido)-2-methylphenyl]-3-methoxy-4-benzyloxybenzamide (0.458 g); NMR: (DMSOd6) 2.18 (s, 3H), 2.96 (s, 6H), 3.82 (s, 3H), 5.12 (s, 2H), 6.9 (m, 1H), 7.16 (t, 1H), 7.21 (d, 2H), 7.3 (t, 2H), 7.4 (m, 5H), 7.57 (m, 3H), 7.78 (d, 1H), 9.75 (s, 1H), 10.18 (s, 1H).
Reaction SMILES: CS[C:3]1[N:8]=[C:7]([OH:9])[CH:6]=[CH:5][N:4]=1.[CH3:10][C:11]1([CH3:20])[CH2:16][CH:15]([NH2:17])[CH2:14][C:13]([CH3:19])([CH3:18])[NH:12]1>>[CH3:10][C:11]1([CH3:20])[CH2:16][CH:15]([NH:17][C:3]2[N:8]=[C:7]([OH:9])[CH:6]=[CH:5][N:4]=2)[CH2:14][C:13]([CH3:19])([CH3:18])[NH:12]1
Reactant: CC1(C)CC(N)CC(C)(C)N1
Reactant: CSc1nccc(O)n1
Product: CC1(C)CC(Nc2nccc(O)n2)CC(C)(C)N1
Reaction time: 2 h
Yield: 93.1 %

Procedure:
Neat 2-methylsulfanyl-pyrimidin-4-ol (5 g, 35 mmol) and 2,2,6,6-tetramethyl-piperidin-4-ylamine (8.243 g, 52.75 mmol) were heated to 170° C. with stirring for 2 hours. After cooling, the brown solid was triturated with ether. Filtration gave 8.16 g (93%) of 2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-ol. This crude (8 g, 32 mmol) was suspended in 160 ml of acetonitrile. Then, 4N-HCl in dioxane (24 ml, 96 mmol) and POCl3 (7.32 ml, 80 mmol) were added successively and the suspension was heated to reflux (105° C. heat bath) for 2 hours. After that, the mixture was cooled, diluted with EtOAc and washed twice with 2N-NaOH, then brine, dried over sodium sulfate and evaporated. Chromatography on silicagel (EtOAc/MeOH/ammonia:2/1/0.02) gave (4-chloro-pyrimidin-2-yl)-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine as a beige solid. Yield: 7.68 g (89%).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[Cl:19][C:20]1[C:25]([F:26])=[CH:24][CH:23]=[C:22]([F:27])[C:21]=1/[CH:28]=[CH:29]/[C:30](O)=[O:31]>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[CH:16][C:15]([NH:18][C:30](=[O:31])/[CH:29]=[CH:28]/[C:21]3[C:22]([F:27])=[CH:23][CH:24]=[C:25]([F:26])[C:20]=3[Cl:19])=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: O=C(O)/C=C/c1c(F)ccc(F)c1Cl
Reactant: CC1(c2ccc(Cn3ccc(N)n3)o2)OCCO1
Product: CC(=O)c1ccc(Cn2ccc(NC(=O)/C=C/c3c(F)ccc(F)c3Cl)n2)o1

Procedure:
Following general procedure B followed by either C or D, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-3-ylamine and (E)-3-(2-chloro-3,6-difluoro-phenyl)-acrylic acid.
Reaction SMILES: [Br:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([N+:10]([O-])=O)[CH:5]=[C:4]([CH3:13])[N+:3]=1[O-].[Cl-].[NH4+]>CCO.O.O.[Fe]>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([NH2:10])[CH:5]=[C:4]([CH3:13])[N:3]=1
Reactant: COc1c([N+](=O)[O-])cc(C)[n+]([O-])c1Br
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COc1c(N)cc(C)nc1Br
Temperature: 90 °C

Procedure:
A mixture of 124D (0.75 g, 2.9 mmol), iron (0.48 g, 8.6 mmol) and ammonium chloride (0.46 g, 8.6 mmol) in EtOH/H2O (10 mL/3 mL) was refluxed (bath temperature 90° C.) for 4 h. After cooling to room temperature, the reaction mixture was diluted with water, extracted with dichloromethane three times. The combined organic phases were dried over Na2SO4, filtered and concentrated to give 124E as a oil.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[C:17](=[O:42])[N:18]([C@H:28]3[CH2:33][CH2:32][C@H:31]([O:34][CH2:35][C:36](N(OC)C)=[O:37])[CH2:30][CH2:29]3)[C:19]3[N:20]([N:25]=[CH:26][CH:27]=3)[C:21]=2[CH2:22][CH2:23][CH3:24])=[CH:11][CH:10]=1)#[N:2].[CH3:43][Mg]Br.C(OCC)(=O)C.[Cl-].[NH4+]>O1CCCC1>[OH:37][CH:36]([CH3:43])[CH2:35][O:34][C@H:31]1[CH2:32][CH2:33][C@H:28]([N:18]2[C:17](=[O:42])[C:16]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:4]4[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:10][CH:11]=3)=[C:21]([CH2:22][CH2:23][CH3:24])[N:20]3[N:25]=[CH:26][CH:27]=[C:19]23)[CH2:29][CH2:30]1
Reactant: C[Mg]Br
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(=O)N(C)OC)CC2)c2ccnn12
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(C)O)CC2)c2ccnn12
Reaction time: 1 h

Procedure:
To a solution of 2-[(trans-4-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propylpyrazolo[1,5-a]pyrimidin-4(5H)-yl}cyclohexyl)oxy]-N-methoxy-N-methylacetamide (0.65 g) in tetrahydrofuran (6 mL) was added dropwise methylmagnesium bromide (1 M tetrahydrofuran solution, 2.3 mL) at 0° C., and the mixture was stirred for 1 hr. Ethyl acetate and then saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in ethanol (6 mL), and sodium borohydride (0.044 g) was added at 0° C. After stirring at 0° C. for 1 hr, ethyl acetate and then saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.57 g, 95%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[CH:10]=[C:11]([C:13]([OH:15])=[O:14])[N:12]=1.[Br:23]N1C(=O)CCC1=O>CN(C)C=O>[Br:23][C:10]1[N:9]([C:16]2[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=2)[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[N:12][C:11]=1[C:13]([OH:15])=[O:14]
Reactant: O=C(O)c1cn(-c2ccc(Cl)cc2)c(-c2ccccc2Cl)n1
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Product: O=C(O)c1nc(-c2ccccc2Cl)n(-c2ccc(Cl)cc2)c1Br
Yield: 49.7 %

Procedure:
A solution of 2-(2-chlorophenyl)-1-(4-chlorophenyl)-1H-imidazole-4-carboxylic acid (50 mg, 0.15 mmol) and N-bromosuccinimide (88 mg, 0.49 mmol) in dimethylformamide (5 mL) was stirred at 75° C. for 3 days. The solution was purified by preparative HPLC to give 5-bromo-2-(2-chlorophenyl)-1-(4-chlorophenyl)-1H-imidazole-4-carboxylic acid as a white solid (30.7 mg, 50%). LC-MS m/z 411.2 (MH+), retention time 2.70 min (method 2).
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[C:8](=[O:13])[NH:9][CH:10]=[CH:11][CH:12]=1.[C:14]([O:17][C@@H:18]1[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:22]([O:28][C:29](=[O:31])[CH3:30])[C@@H:21]([CH2:32][O:33][C:34](=[O:36])[CH3:35])[O:20][CH:19]1Br)(=[O:16])[CH3:15].[Al]>ClCCl.C(=O)([O-])[O-].[Ag+2]>[C:14]([O:17][C@@H:18]1[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:22]([O:28][C:29](=[O:31])[CH3:30])[C@@H:21]([CH2:32][O:33][C:34](=[O:36])[CH3:35])[O:20][C@H:19]1[O:13][C:8]1[C:7]([CH:3]2[CH2:4][CH2:5][CH2:6][N:2]2[CH3:1])=[CH:12][CH:11]=[CH:10][N:9]=1)(=[O:16])[CH3:15]
Reactant: CN1CCCC1c1ccc[nH]c1=O
Reactant: CC(=O)OC[C@H]1OC(Br)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Agent: [Al]
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@@H](Oc2ncccc2C2CCCN2C)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
(±)-3-(1-methyl-2-pyrrolidinyl)-2-pyridone (1)(2.0 g) and 2,3,4,6-tetra-O-acetylglucopyranosyl bromide (4a)(5.6 g) were dissolved in dichloromethane (40 ml). To this solution, silver carbonate (1.8 g) was added. The mixture was stirred at room temperature for 24 hours while the vessel was shielded from light by an aluminum sheet. Solid material was filtered off, and the filtrate was concentrated under reduced pressure. As a result, (±)-3-(1-methyl-2-pyrrolidinyl)-2-pyridyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (5a) was obtained. The compound (5a) obtained as above was subjected to the experiment of the following example without purification.
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH2:5][C:6]#[C:7][C:8]1[C:9]([C:18]([O:20][CH3:21])=[O:19])=[CH:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[N:12][CH:13]=1)#[N:2]>CO.[Pd]>[C:1]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[C:9]([C:18]([O:20][CH3:21])=[O:19])=[CH:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[N:12][CH:13]=1)#[N:2]
Reactant: COC(=O)c1cc(C(=O)OC)c(C#CCCCC#N)cn1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(C(=O)OC)c(CCCCCC#N)cn1
Reaction time: 4 h

Procedure:
64 mg of dimethyl 5-(5-cyano-1-pentinyl)-pyridine-2,4-dicarboxylate (from Example 11) are dissolved in 25 ml of methanol and, after addition of the palladium catalyst (10% strength on charcoal), are hydrogenated. The reaction has ended after 4 hours (thin layer control). The catalyst is filtered off and the solution is concentrated in vacuo. The colorless oil is chromatographed on silica gel.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([NH:17][CH2:18][C:19]([NH:21][C:22]2[C:27]([CH:28]([CH3:30])[CH3:29])=[CH:26][CH:25]=[CH:24][C:23]=2[CH:31]([CH3:33])[CH3:32])=[O:20])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>[CH3:30][CH:28]([C:27]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:31]([CH3:32])[CH3:33])[C:22]=1[NH:21][C:19](=[O:20])[CH2:18][NH:17][CH:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([CH2:3][OH:2])[CH:5]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH3:29]
Reactant: COC(=O)c1cccc(C(NCC(=O)Nc2c(C(C)C)cccc2C(C)C)c2ccccc2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: CC(C)c1cccc(C(C)C)c1NC(=O)CNC(c1ccccc1)c1cccc(CO)c1

Procedure:
The title compound was prepared by the reduction of the product of Example 149 by LiAlH4 at room temperature, mp 57°-62° C.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.[C:21](Cl)(=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]/[CH:29]=[CH:30]\[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]>C(Cl)Cl>[C:21]([NH:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)(=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]/[CH:29]=[CH:30]\[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]
Reactant: NCCCSc1ccncc1
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCC/C=C\CCCCCCCC(=O)NCCCSc1ccncc1
Yield: 83.7 %

Procedure:
To a solution of 700 mg (2.90 mmol) of 4-(3-aminopropylthio)pyridine dihydrochloride and 1.62 ml (11.6 mmol) of triethylamine in 30 ml of methylene chloride was added 1.55 ml (3.48 mmol) of oleoyl chloride under ice-cooling with stirring and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with an aqueous saturated sodium bicarbonate solution and water and dried. The solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain the powder which was washed with hexane and dried to obtain 1.05 g of the desired compound (83.7%, colorless powder), mp: 50.0°-50.5° C.
Reaction SMILES: [CH2:1]([O:7][N:8]=[C:9]([C:15](=O)[CH2:16]Cl)[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[NH2:19][C:20]([NH2:22])=[S:21].C(O)C>O>[NH2:22][C:20]1[S:21][CH:16]=[C:15]([C:9](=[N:8][O:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[N:19]=1
Reactant: NC(N)=S
Reactant: CCCCCCON=C(C(=O)CCl)C(=O)OCC
Solvent: CCO
Solvent: O
Product: CCCCCCON=C(C(=O)OCC)c1csc(N)n1
Yield: 49 %

Procedure:
Ethyl 2-n-hexyloxyimino-4-chloro-3-oxobutyrate (syn isomer, 55.6 g,), thiourea (15.2 g.), sodium acetate 3-hydrate (27.2 g.), ethanol (280 ml.) and water (140 ml.) were treated in a similar manner to that of Example F-(3) to give ethyl 2-(2-aminothiazol-4-yl)-2-n-hexyloxyiminoacetate (syn isomer, 29.3 g.), mp 77° to 78° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[C:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[N:15]=[CH:16][CH:17]=2)[N:12]=[C:11](C(O)=O)[CH:10]=1.C1(P([N:44]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>C(O)(C)(C)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[C:14]([C:19]3[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=3[F:25])[N:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([NH2:44])[CH:10]=1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: O=C(O)c1cc(-c2ccc(F)cc2F)c2ccnc(-c3c(F)cccc3F)c2n1
Solvent: CC(C)(C)O
Solvent: CCN(CC)CC
Product: Nc1cc(-c2ccc(F)cc2F)c2ccnc(-c3c(F)cccc3F)c2n1
Temperature: 100 °C
Reaction time: 2.5 h
Yield: 114.8 %

Procedure:
To a suspension of the title compound from Example 1 (100 mg, 0.25 mmol) in tert-butanol (2.4 mL) were added diphenylphosphoryl azide (DPPA) (0.07 mL, 0.32 mmol) and triethylamine (0.045 mL, 0.32 mmol). The mixture was heated at 100° C. for 75 minutes. The solvent was evaporated and the mixture redissolved in HCl (4M in dioxane, 2 mL) and stirred at room temperature for 2.5 hours. Subsequently, 4% aqueous sodium bicarbonate (40 mL) was added to the mixture and the reaction was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure to give 106 mg of a yellowish oil. The mixture was purified by column chromatography (C-18 silica from Waters©, reverse phase water/(acetonitrile/methanol 50:50) as eluent [0.1% v/v ammonium formate buffered] 0% to 100%). The organic solvent from the appropriate fractions was evaporated and the aqueous phase basified to pH 10 with ammonium hydroxide. This was extracted with ethyl acetate, dried over sodium sulphate and the solvent removed under reduced pressure to give the title compound as a white solid (55 mg, 60%).
Reaction SMILES: [N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[CH2:20](N)[CH2:21][CH3:22]>CC1C=CC=CC=1C>[CH2:20]([NH:1][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)[CH2:21][CH3:22]
Reactant: CCCN
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Solvent: Cc1ccccc1C
Product: CCCNc1cccc2c1C(=O)c1ccccc1C2=O
Yield: 94.3 %

Procedure:
A mixture of 50.6 g of 1-nitro-anthraquinone (99% pure) and 240 ml of o-xylene is reacted with 118 g of n-propylamine (molar ratio 10:1) at a temperature of 170° C. and under a pressure of 30 bars and for a reaction time of 80 minutes. Working up analogously to Example 1 gives 50 g (94% of theory) of 1-n-propylamino-anthraquinone, in which no further 1-nitro-anthraquinone can be detected.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:8]=2[CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH:19]([C:24]([F:27])([F:26])[F:25])[C:20]([F:23])([F:22])[F:21])=[O:17])[CH2:12][CH2:11]2)[CH2:3]1.CCN(C(C)C)C(C)C.[C:42](Cl)(=[O:44])[CH3:43]>C(Cl)Cl>[C:42]([NH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:8]=2[CH2:9][N:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][CH:19]([C:24]([F:27])([F:26])[F:25])[C:20]([F:21])([F:22])[F:23])=[O:17])[CH2:14][CH2:15]2)[CH2:3]1)(=[O:44])[CH3:43]
Reactant: CC(=O)Cl
Reactant: N[C@@H]1CCN(c2cc(Cl)ccc2CN2CCN(C(=O)OC(C(F)(F)F)C(F)(F)F)CC2)C1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(=O)N[C@@H]1CCN(c2cc(Cl)ccc2CN2CCN(C(=O)OC(C(F)(F)F)C(F)(F)F)CC2)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 99.1 %

Procedure:
A 4 mL vial was charged with (R)-1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(3-aminopyrrolidin-1-yl)-4-chlorobenzyl)piperazine-1-carboxylate (28 mg, 0.057 mmol), a magnetic stirbar, CH2Cl2 (2 mL), and DIPEA (30 μL, 0.172 mmol). The reaction was cooled to 0° C. and an acetyl chloride solution (7 mg, 0.086 mmol, in 1 mL CH2Cl2) was added dropwise. After stirring for 30 min at 0° C., the reaction was quenched with sat Na2CO3 and extracted with CH2Cl2 (3×). The organics were dried (Na2SO4), filtered, and concentrated. The residue was chromatographed on a silica gel column (100% to 10% MeOH in CH2Cl2) and yielded (R)-1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(3-acetamidopyrrolidin-1-yl)-4-chlorobenzyl)piperazine-1-carboxylate (30 mg, 35%). 1H NMR 400 MHz (CDCl3) δ 7.31 (d, J=8.2 Hz, 1H), 6.91 (dd, J=8.1, 1.8 Hz, 1H), 6.86 (d, J=1.9 Hz, 1H), 5.84-5.70 (m, 2H), 4.62-4.50 (m, 1H), 3.59-3.53 (m, 4H), 3.50 (s, 2H), 3.48-3.44 (m, 1H), 3.43-3.33 (m, 1H), 3.20-3.10 (m, 2H), 2.50-2.42 (m, 4H), 2.34 (td, J=13.4, 7.6 Hz, 1H), 2.01 (s, 3H), 1.91-1.79 (m, 1H). LCMS (ESI, m/z): 531 [M+H]+.
Reaction SMILES: [ClH:1].[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH:14](N)[N:15](C(OC(C)(C)C)=O)[CH2:16][C@H:17]([OH:38])[C@@H:18]([NH:26][C:27](=[O:37])[C@H:28]([CH:34]([CH3:36])[CH3:35])[NH:29][C:30]([O:32][CH3:33])=[O:31])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:10][CH:9]=1.C[N:48](C=O)C>O1CCOCC1>[ClH:1].[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]([NH2:48])[CH2:16][C@H:17]([OH:38])[C@@H:18]([NH:26][C:27](=[O:37])[C@H:28]([CH:34]([CH3:36])[CH3:35])[NH:29][C:30]([O:32][CH3:33])=[O:31])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:10][CH:9]=1
Reactant: CN(C)C=O
Reactant: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)CN(C(=O)OC(C)(C)C)C(N)c1ccc(-c2ccccn2)cc1)C(C)C
Agent: Cl
Solvent: C1COCCO1
Product: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)CN(N)Cc1ccc(-c2ccccn2)cc1)C(C)C
Reaction time: 3.5 h

Procedure:
Analogously to Example 37f), 30 ml of 4 M HCl in dioxane are added to 3.5 g (5.65 mmol) of 1-[4-(pyridin-2-yl)-phenyl]-4-(S)-hydroxy-2-N-Boc-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane and the mixture is diluted with 5 ml of DMF. After 3.5 hours, the mixture is worked up. The title compound is obtained: TLC: Rf =0.53 (methylene chloride/methanol: 9/1); HPLC20-100 : tRet =8.00; FAB MS (M+H)+ =520.