Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])/[C:4](/[C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)=[CH:5]\[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1.[H-].[Na+].F[C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][CH:28]=1.O>CN(C=O)C>[CH3:1][O:2][C:3](=[O:23])/[C:4](/[C:16]1[CH:17]=[CH:18][C:19]([O:22][C:27]2[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][CH:28]=2)=[CH:20][CH:21]=1)=[CH:5]\[C:6]1[CH:7]=[C:8]([O:14][CH3:15])[CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1
Reactant: COC(=O)/C(=C\c1cc(OC)cc(OC)c1)c1ccc(O)cc1
Reactant: O=Cc1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)/C(=C\c1cc(OC)cc(OC)c1)c1ccc(Oc2ccc(C=O)cc2)cc1
Temperature: 80 °C
Yield: 74.2 %

Procedure:
Under argon, 20 (0.60 g, 1.9 mmol) was dissolved in dry DMF (4 mL) and to this sodium hydride (60% in oil, 0.09 g, 2.28 mmol) was added. To the resulting orange solution, 4-fluorobenzaldehyde (0.25 mL, 2.28 mmol) was added and heated at 80° C. for 18 h. The reaction mixture was cooled to room temperature, water (10 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The crude product obtained after evaporation was purified by chromatography over silica gel and elution with a mixture of hexane-ethyl acetate (4:1) to yield 21 as white solid (0.59 g, 74%): 1HNMR(400 MHz, CDCl3) δ 9.93 (s, 1H), 7.86 (d, J=8.8 Hz, 2H), 7.49 (d, J=8.8 Hz, 2H), 7.10 (overlapped d, J=8.8 Hz, 2H), 7.08 (overlapped d, J=8.8 Hz, 2H), 6.96 (s, 1H), 6.53 (dd, J=2.8 Hz, 2H), 6.43 (t, J=2.0 Hz, 1H), 3.80(s, 3H), 3.79 (s, 6H).
Reaction SMILES: [CH:1]1([CH:7]([CH3:11])[C:8]([OH:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:12]=[C:13]([CH3:15])[CH3:14].S(=O)(=O)(O)O>CCOCC>[CH:1]1([CH:7]([CH3:11])[C:8]([O:10][C:13]([CH3:15])([CH3:14])[CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C(=O)O)C1CCCCC1
Reactant: C=C(C)C
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: CC(C(=O)OC(C)(C)C)C1CCCCC1
Temperature: 0 °C
Reaction time: 40 h
Yield: 11 %

Procedure:
Into a 500 ml round bottom flask 30 g of 2-cyclohexylpropionic acid and 200 ml of ether were charged and cooled to 0° C. After 100 g of isobutene gas was introduced, 0.5 g of sulfuric acid was charged into the mixture, the mixture was then stirred at 0° C. for 40 hours. The reaction mixture was washed with water and distilled under reduced pressure to obtain 4.5 g of tert-butyl 2-cyclohexylpropionate having a woody and floral odor (yield: 11%, purity: 98.7%).
Reaction SMILES: [C:1]1([CH2:7][C:8](=[O:10])[CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:11][C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[C:19]=1[OH:20])[CH:15]=O.Cl>CC(O)C>[OH:11][C:12]1[CH:13]=[C:14]([CH:15]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8](=[O:10])[CH3:9])[CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[C:19]=1[OH:20]
Reactant: O=Cc1cc(O)c(O)c([N+](=O)[O-])c1
Reactant: CC(=O)Cc1ccccc1
Agent: Cl
Solvent: CC(C)O
Product: CC(=O)C(=Cc1cc(O)c(O)c([N+](=O)[O-])c1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution containing 2.68 g of 3-phenyl-2-propanone and 3.66 g of 3,4-dihydroxy-5-nitrobenzaldehyde in 80 ml of 2-propanol was saturated with hydrogen chloride gas at 20° C. The mixture was stirred for 4 h at room temperature, filtered and washed with 2-propanol. The product was recrystallized from methanol. Yield 1.34 g, mp 170°-176° C.
Reaction SMILES: [CH:1]([C:3]([OH:10])([CH2:7][CH2:8][CH3:9])[CH2:4][CH2:5][CH3:6])=[CH2:2].Br[C:12]1[CH:13]=[C:14]([CH:18]([OH:28])[CH2:19][CH2:20][NH:21][C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH:15]=[CH:16][CH:17]=1>>[F:24][C:23]([F:25])([F:26])[C:22]([NH:21][CH2:20][CH2:19][CH:18]([OH:28])[C:14]1[CH:15]=[CH:16][CH:17]=[C:12](/[CH:2]=[CH:1]/[C:3]([OH:10])([CH2:7][CH2:8][CH3:9])[CH2:4][CH2:5][CH3:6])[CH:13]=1)=[O:27]
Reactant: C=CC(O)(CCC)CCC
Reactant: O=C(NCCC(O)c1cccc(Br)c1)C(F)(F)F
Product: CCCC(O)(/C=C/c1cccc(C(O)CCNC(=O)C(F)(F)F)c1)CCC

Procedure:
Coupling of 4-vinylheptan-4-ol with N-(3-(3-bromophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide following the method in Example 111 except the reaction was done in 1 hour at 90° C. gave (E)-2,2,2-trifluoro-N-(3-hydroxy-3-(3-(3-hydroxy-3-propylhex-1-enyl)phenyl)propyl)acetamide as a light color oil. Yield (42 g, 45%): 1H NMR (400 MHz, MeOD) δ 7.39 (s, 1H), 7.26-7.27 (m, 2H), 7.18-7.20 (m, 1H), 6.54 (d, J=16 Hz, 1H), 6.23 (d, J=16 Hz, 1H), 4.67 (t, J=6.4 Hz, 1H), 3.37 (t, J=7.2 Hz, 2H), 1.92-1.97 (m, 2H), 1.55-1.59 (m, 4H), 1.30-1.46 (m, 4H), 0.91 (t, J=7.6 Hz, 6H).
Reaction SMILES: [C:1]1([CH3:14])[CH:6]=[CH:5][C:4]([S:7]([NH:10][C:11]([NH2:13])=[S:12])(=[O:9])=[O:8])=[CH:3][CH:2]=1.Br[CH2:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([CH3:26])[CH:20]=1)=O>C(O)C>[OH:25][C:22]1[CH:23]=[CH:24][C:19]([C:17]2[N:13]=[C:11]([NH:10][S:7]([C:4]3[CH:3]=[CH:2][C:1]([CH3:14])=[CH:6][CH:5]=3)(=[O:9])=[O:8])[S:12][CH:16]=2)=[CH:20][C:21]=1[CH3:26]
Reactant: Cc1ccc(S(=O)(=O)NC(N)=S)cc1
Reactant: Cc1cc(C(=O)CBr)ccc1O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)Nc2nc(-c3ccc(O)c(C)c3)cs2)cc1
Reaction time: 72 h
Yield: 24.8 %

Procedure:
A solution of 26 g of 4-toluenesulfonyl-thiourea in 225 ml of ethanol was treated with 25.9 g of 2-bromo-1-(4-hydroxy-3-methyl-phenyl)-ethanone, left to stand at room temperature for 3 days and then boiled for a brief period. The reaction mixture was evaporated to dryness in a vacuum and subsequently partitioned between water and ethyl acetate. The aqueous phase was extracted once with ethyl acetate, the organic phases were combined, dried with sodium sulphate and concentrated. The residue was chromatographed on 500 g of Kieselgel 60 with ethyl acetate/hexane (1:1) as the eluent. The product-containing fractions were concentrated and, after recrystallization from 50% ethanol, yielded 10.1 g of N-[4-(4-hydroxy-3-methyl-phenyl)-thiazol-2-yl]-4-methyl-benzenesulfonamide as colourless crystals.
Reaction SMILES: [C:1]([O:4][C@@H:5]([C@H:8]([C@@H:13]([C@@H:18]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:19][C:20](=[O:22])[CH3:21])[O:14][C:15](=[O:17])[CH3:16])[O:9][C:10](=O)C)C=O)(=[O:3])[CH3:2].C[Si]([N:32]=[N+:33]=[N-:34])(C)C>C(Cl)Cl>[C:25]([O:24][C@H:23]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]([O:14][C:15](=[O:17])[CH3:16])[C@@H:8]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[O:9][C@@H:10]1[N:32]=[N+:33]=[N-:34])(=[O:27])[CH3:26]
Reactant: CC(=O)OC[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](C=O)OC(C)=O
Reactant: C[Si](C)(C)N=[N+]=[N-]
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@H](N=[N+]=[N-])[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
About 2 ml. stannic chloride is added to a solution of 8 grams of D-mannose pentaacetate and 2.6 ml. trimethylsilyl azide in 180 ml. methylene chloride, and the resulting mixture is stirred at a temperature of about 25° C. for a period of approximately six hours. The reaction solution is diluted with an additional 100 ml. of methylene chloride, and the resulting methylene chloride solution is washed successively with water, with aqueous sodium bicarbonate solution, again with water, and dried over anhydrous sodium sulfate. The dry methylene chloride solution is evaporated in vacuo to a syrup which crystallizes upon standing to give approximately 7.6 grams of 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl azide; m.p. 52°-53° C. (after recrystallization from 2-propanol); [α]D25 +116°, (c 1.02, chloroform).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[C:7]([C:10]([OH:12])=O)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C(Cl)(=O)C([Cl:16])=O>C(Cl)Cl.CN(C)C=O>[S:1]1[C:5]2[CH:6]=[C:7]([C:10]([Cl:16])=[O:12])[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1ccc2ncsc2c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1ccc2ncsc2c1
Temperature: 30 °C
Reaction time: 2 h
Yield: 150.4 %

Procedure:
Under a nitrogen atmosphere, benzothiazole-6-carboxylic acid (1.014 g, 5.6 mmol) was dissolved in methylene chloride (25 mL). Five drops of N,N-dimethylforamide was added. Oxalyl chloride (0.5 mL, 5.6 mmol) was slowly added. After 2 hrs, the reaction was heated to 30° C. for 16 hrs. The reaction was concentrated in vacuo to yield benzothiazole-6-carbonyl chloride (1.665 g, quant., light yellow powder)
Reaction SMILES: N1CCCCC1.C1C2C(COC(=O)[NH:23][C@H:24]([C:45]([OH:47])=[O:46])[CH2:25][CH2:26][CH2:27][CH2:28][N:29]([CH2:38][C:39]3[N:40]([CH3:44])[CH:41]=[CH:42][N:43]=3)[CH2:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])C3C(=CC=CC=3)C=2C=CC=1>CN(C=O)C>[NH2:23][C@@H:24]([CH2:25][CH2:26][CH2:27][CH2:28][N:29]([CH2:30][C:31]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:37])[CH2:38][C:39]1[N:40]([CH3:44])[CH:41]=[CH:42][N:43]=1)[C:45]([OH:47])=[O:46]
Reactant: Cn1ccnc1CN(CCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O)CC(=O)OC(C)(C)C
Solvent: CN(C)C=O
Solvent: C1CCNCC1
Product: Cn1ccnc1CN(CCCC[C@H](N)C(=O)O)CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 98.3 %

Procedure:
Piperidine (0.40 mL) was added to a solution of (S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-10-((1-methyl-1H-imidazol-2-yl)methyl)-3,12-dioxo-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid (190 mg, 0.33 mmol) in DMF (2.0 mL). The mixture was stirred at room temperature for 2 hrs. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Amberchrom to afford (S)-2-amino-6-((2-tert-butoxy-2-oxoethyl)((1-methyl-1H-imidazol-2-yl)methyl)amino)hexanoic acid (115 mg, 100%). 1H NMR (400 MHz, DMSO) 7.27 (brs, 1H), 7.04 (s, 1H), 6.72 (s, 1H), 3.73 (s, 2H), 3.64 (s, 3H), 3.15 (s, 2H), 3.04 (dd, J=6.8, 5.2 Hz, 1H), 2.47 (t, J=7.2 Hz, 2H), 1.65-1.46 (m, 2H), 1.39 (s, 9H), 1.30-1.21 (m, 4H); MS (ESI), 355 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16].Cl.[Cl:18][C:19]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:20]=1[NH2:21].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:20]=1[NH:21][C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16]
Reactant: N#Cc1cnc2c(c1Cl)C=C1N=CN=C1C2
Reactant: COc1ccc(Cl)c(N)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CCOCCO
Product: COc1ccc(Cl)c(Nc2c(C#N)cnc3c2C=C2N=CN=C2C3)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 62.4 %

Procedure:
A mixture of 0.2 g (0.87 mmol) of 8-chloroimidazo[4,5-g]quinoline-7-carbonitrile, 0.22 g (1.04 mmol) of 2-chloro-5-methoxyaniline hydrochloride and 0.1 g (0.87 mmol) of pyridine hydrochloride in 5.0 mL of 2-ethoxyethanol is heated at reflux temperature for 1 hour, cooled to room temperature, poured into a saturated solution of sodium bicarbonate and stirred for 0.5 hour. The solid is collected by filtration, washed with water and dried. The solid is purified by silica gel chromatography utilizing a gradient of methylene chloride/methanol (97:3 to 90:10) to yield 0.19 g of 8-(2-chloro-5-methoxy-phenylamino)imidazo[4,5-g]quinoline-7-carbonitrile as beige solid, mp 296–298° C.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1I)(=[O:3])[CH3:2].[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[C:31]1[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cnccc1I
Reactant: OB(O)c1ccc(F)cc1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cnccc1-c1ccc(F)cc1

Procedure:
By following a procedure analogous to Example 27 starting from the 4-iodo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside obtained according to Preparation 21 and 4-fluorophenylboronic acid, 4-(4-fluorophenyl)-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside is obtained in the form of a white solid (yield=47%).
Reaction SMILES: [C:1]1([N:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(N(C2C=CC=CC=2)/[C:28](/[C:36]2[CH:41]=[CH:40]C=CC=2)=[CH:29]/[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)C=CC=CC=1>>[C:15]1([N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:40][C:41]2[C:31]3[C:30](=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:29]=[CH:28][CH:36]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: C(=C(\c1ccccc1)N(c1ccccc1)c1ccccc1)\c1ccccc1
Reactant: c1ccc(CN(c2ccccc2)c2ccccc2)cc1
Product: C(=C(c1ccccc1)N(c1ccccc1)c1ccccc1)c1cccc2ccccc12

Procedure:
This compound was synthesized from diphenylbenzylamine and N-phenyl-1-naphthaldimine under the same conditions outlined for (E)-1-(diphenylamino)-1-phenyl-2-phenylethylene above. Recrystallization from ethyl acetate/methanol gave small crystals mp 170°-2° C. 1H NMR (200 MHz, CDCl3) δ (assignment): 6.60-6.90 (m, 2H, aromatic), 6.80-7.38 (m, 15H, aromatic), 7.52-7.85 (m, 6H, aromatic). MS [m/e (70 eV, % of base peak)] C10H7CHCPhNPh2 397 (M+., 43.1), 180 (PhCNPh+, 100), 77 (Ph+, 43.2); HRMS (m/z) for C30H23N (M+.), calcd. 397.183 found 397.195.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH2:10])[S:8][CH:9]=1)=[O:4].[C:11]([O:15][C:16]([NH:18][C@@H:19]([C@H:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:24])[C:20](O)=[O:21])=[O:17])([CH3:14])([CH3:13])[CH3:12].ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:20](=[O:21])[C@@H:19]([NH:18][C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])[C@H:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH3:24])[S:8][CH:9]=1)=[O:4]
Reactant: C[C@@H](c1ccccc1)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: COC(=O)c1csc(N)n1
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1csc(NC(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)c2ccccc2)n1
Yield: 42.8 %

Procedure:
2-Amino-thiazole-4-carboxylic acid methyl ester (0.57 g, 3.62 mmol) and (2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyric acid (Acros) (1.01 g, 3.62 mmol), 1-hydroxybenzotriazole and (0.59 g, 4.34 mmol) and O-benzeotrazol-1-yl-N,N,N′,N′-tetramethyluroniumhexaflurorophosphate (1.65 g, 4.34 mmol) in N,N-dimethylformamide (8 mL) were stirred at ambient temperature for 24 hours. The mixture was diluted with ethyl acetate, washed with water, brine and dried (magnesium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel gradient eluted with 0.2-1.5% methanol in dichloromethane gave 2-((2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester (0.65 g, 43%).
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][CH:7]2[C:13](=[O:14])[NH:12][C:10](=[O:11])[CH:9]([C:15]([OH:17])=[O:16])[CH2:8]2)=[CH:4][CH:3]=1.[Br:20]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:20][CH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH:7]2[C:13](=[O:14])[NH:12][C:10](=[O:11])[CH:9]([C:15]([OH:17])=[O:16])[CH2:8]2)=[CH:18][CH:19]=1
Reactant: Cc1ccc(OC2CC(C(=O)O)C(=O)NC2=O)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=C1NC(=O)C(C(=O)O)CC1Oc1ccc(CBr)cc1
Temperature: 25 °C
Yield: 89.9 %

Procedure:
A solution of 1.3 g (5.2 mmol) of 4-(4-methylphenoxy)carboxyglutarimide, 1.0 g (5.7 mmol) of N-bromosuccinimide and 0.02 g of benzoyl peroxide in 30 ml of carbon tetrachloride was refluxed for 16 hours, cooled to room temperature, evaporated and the residue dissolved in 200 ml of ethyl acetate. The EtOAc layer was washed with water, dried over Na2SO4 and evaporated to give 1.6 g of the crude product.
Reaction SMILES: [CH:1]([CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)=[O:26])([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[O:15])[C:5]1=[O:35])=O.Cl.[NH2:37][OH:38].C([O-])(=O)C.[Na+]>CO.O>[OH:38][N:37]=[CH:1][CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:24][C:25]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)=[O:26])([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[O:15])[C:5]1=[O:35]
Reactant: Cc1ccc(NC(=O)CC2(NC(=O)Nc3ccc(C)cc3)C(=O)N(CC=O)c3ccccc32)cc1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cc1ccc(NC(=O)CC2(NC(=O)Nc3ccc(C)cc3)C(=O)N(CC=NO)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.2 %

Procedure:
In 1 ml of methanol was dissolved 0.050 g of (+)-1-formylmethyl-3-(4-methylphenyl)aminocarbonylmethyl-3-(N'-(4-methylphenyl)ureido)indolin-2-one, and a solution of 0.021 g of hydroxylamine hydrochloride and 0.021 g of sodium acetate in 1 ml of water was added thereto. The resulting mixture was stirred at room temperature for 1 hour and concentrated. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (dichloromethane/ethyl acetate=1/1) to give 0.045 g of the title compound.
Reaction SMILES: [OH:1][CH2:2][C:3]([NH:6][C:7](=[O:9])[CH3:8])([CH3:5])[CH3:4].N[C:11]1(CO)CCC[CH2:12]1.CC#N.O.CC#N>O>[OH:1][CH2:2][C:3]1([NH:6][C:7](=[O:9])[CH3:8])[CH2:5][CH2:12][CH2:11][CH2:4]1
Reactant: NC1(CO)CCCC1
Reactant: CC(=O)NC(C)(C)CO
Solvent: CC#N
Solvent: O
Product: CC(=O)NC1(CO)CCCC1

Procedure:
The title compound is prepared analogously as described for N-(2-hydroxy-1,1-dimethyl-ethyl)-acetamide from (1-amino-cyclopentyl)-methanol. MS (LC-MS): [M+H]+=158.2. tR (HPLC, Waters sun fire C18 column, 5-95% CH3CN/H2O/3.5 min, 95% CH3CN/H2O, 2 min, CH3CN and H2O containing 0.1% TFA, flow: 0.8 mL/min): 1.76 min.
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][C:2]=1[C:14](=[O:23])[CH:15]=[CH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[C:24]([O:31][CH3:32])(=[O:30])[CH2:25][C:26]([O:28][CH3:29])=[O:27]>>[CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][C:2]=1[C:14](=[O:23])[CH2:15][CH:16]([CH:25]([C:24]([O:31][CH3:32])=[O:30])[C:26]([O:28][CH3:29])=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: COC(=O)CC(=O)OC
Reactant: O=C(C=Cc1ccccc1)c1ccc2c(c1)[nH]c1ccccc12
Product: COC(=O)C(C(=O)OC)C(CC(=O)c1ccc2c(c1)[nH]c1ccccc12)c1ccccc1

Procedure:
By a procedure similar to that of example 1.59.2, starting from 1-(9H-carbazol-2-yl)-3-phenylprop-2-en-1-one and dimethyl malonate, dimethyl 2-(3-(9H-carbazol-2-yl)-3-oxo-1-phenylpropyl)malonate was obtained as colourless solid.
Reaction SMILES: [CH2:1]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[CH:15]=2)[N:10]([CH3:24])[C:9]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:38][C:39]#[N:40]>CC(C)=O>[CH2:1]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:38][C:39]#[N:40])=[CH:19][CH:18]=3)[CH:15]=2)[N:10]([CH3:24])[C:9]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#CCBr
Reactant: Cn1c(-c2ccccc2)c(Cc2ccccc2)c2cc(-c3ccc(O)cc3)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Cn1c(-c2ccccc2)c(Cc2ccccc2)c2cc(-c3ccc(OCC#N)cc3)ccc21

Procedure:
The desired product was prepared using a procedure similar to step 5 of example 3. Thus, 4-(3-benzyl-1-methyl-2-phenyl-1H-indol-5-yl)-phenol (0.140 g, 0.359 mmol) was reacted with K2CO3 (0.065 g, 0.467 mmol) and bromoacetonitrile (0.056 g, 0.467 mmol) in acetone (5 ml) to give the product (0.141 g, 0.329 mmol, 92%) as a glass-like solid. 1H NMR (DMSO-d6) δ 3.62 (s, 3H), 4.04 (s, 2H), 5.18 (s, 2H), 7.07-7.13 (m, 5H), 7.18 (t, J=7.5 Hz, 2H), 7.44-7.49 (m, 4H), 7.52-7.55 (m, 3H), 7.57-7.60 (m, 3H); [ESI(+)], m/z 429 (M+H)+.
Reaction SMILES: [C@H:1]([NH2:5])([CH2:3][CH3:4])[CH3:2].Br[C:7]1[N:11]([C@@H:12]2[O:18][C@H:17]([CH3:19])[C@@H:15]([OH:16])[C@H:13]2[OH:14])[C:10]2[CH:20]=[C:21]([Cl:25])[C:22]([Cl:24])=[CH:23][C:9]=2[N:8]=1>>[Cl:24][C:22]1[C:21]([Cl:25])=[CH:20][C:10]2[N:11]([C@@H:12]3[O:18][C@H:17]([CH3:19])[C@@H:15]([OH:16])[C@H:13]3[OH:14])[C:7]([NH:5][C@@H:1]([CH2:3][CH3:4])[CH3:2])=[N:8][C:9]=2[CH:23]=1
Reactant: C[C@H]1O[C@@H](n2c(Br)nc3cc(Cl)c(Cl)cc32)[C@H](O)[C@@H]1O
Reactant: CC[C@@H](C)N
Product: CC[C@@H](C)Nc1nc2cc(Cl)c(Cl)cc2n1[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
Temperature: 80 °C
Reaction time: 24 h
Yield: 53.8 %

Procedure:
Following General Procedure V, (R)-sec-butylamine (Aldrich, 1.39 mL, 13.70 mmol), and 2-bromo-5,6-dichloro-1-(5-deoxy-beta-D-ribofuranosyl)-1H-benzimidazole (250 mg, 0.65 mmol) were reacted for 65 h. Additional (R)-sec-butylamine (1.39 mL, 13.70 mmol) was added, and the reaction continued to stir at 80° C. for 24 h. Purification on a silica gel column with 1:1 ethyl acetate:hexanes gave the title compound (130 mg, 0.35 mmol, 53%); MS (EI): m/z (rel. intensity) 374 (0.13, M+); 1H NMR (DMSO-d6) δ7.39 (s, 1H, Ar—H), 7.32 (s, 1H, Ar—H), 6.59 (d, 1H, NH, J=7.8 Hz), 5.72 (d, 1H, CH, J=6.6 Hz), 5.26 (m, 2H, overlapping OH), 4.27 (m, 1H, CH), 4.04-3.78 (m, 3H, overlapping CH), 1.61-1.51 (m, 2H, CH2), 1.38 (d, 3H, CH3, J=6.5 Hz), 1.17 (d, 3H, CH3, J=6.5 Hz), 0.89 (t, 3H, CH3, J=14.9 Hz).
Reaction SMILES: Cl[C:2]1[C:3]2[S:23][CH2:22][CH2:21][C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[N:7]=1.[N-:24]=[N+:25]=[N-:26].[Na+]>CN(C)C=O>[N:24]([C:2]1[C:3]2[S:23][CH2:22][CH2:21][C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[N:7]=1)=[N+:25]=[N-:26]
Reactant: [N-]=[N+]=[N-]
Reactant: Clc1ccc(N2CCN(c3nc(Cl)c4c(n3)CCS4)CC2)cc1
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=Nc1nc(N2CCN(c3ccc(Cl)cc3)CC2)nc2c1SCC2
Temperature: 100 °C
Reaction time: 4 h
Yield: 95 %

Procedure:
0.950 g (2.59 mmol) of 4-chloro-2-[4-(4-chlorophenyl)piperazin-1-yl]-6,7-dihydrothieno[3,2-d]pyrimidine (III) is placed in 20 mL of dimethylformamide and 0.900 g (13.84 mmol) of sodium azide is added. The reaction mixture is stirred for 4 hours at 100° C. It is then concentrated by evaporation, the residue is cooled in the ice bath and combined with water. The precipitate formed is suction filtered, washed, and dried. 0.920 g of product IV (76%) is obtained and used further in the crude state.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=2)=[N:7][CH:8]=1.C([O-])(=O)C.[NH4+].[N+:25]([CH3:28])([O-:27])=[O:26]>>[N+:25]([CH:28]=[CH:14][C:13]1[CH:16]=[CH:17][C:10]([O:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:19])([F:18])[F:1])=[CH:8][N:7]=2)=[CH:11][CH:12]=1)([O-:27])=[O:26]
Reactant: O=Cc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Product: O=[N+]([O-])C=Cc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
Temperature: 95 °C
Reaction time: 8 h
Yield: 56 %

Procedure:
Entire reaction was performed under argon using syringe septa technique. 4-(5-trifluoromethyl-pyridin-2-yloxy)-benzaldehyde (2.170 mmol, 1 eq) and ammonium acetate (1.736 mmol, 0.8 eq) were dissolved in nitromethane (3 ml) and reaction mixture was stirred at 95° C. overnight. The volatile was removed in vacuo and the residue was partitioned between DCM and water. Organic layers were combined, washed with brine, dried over MgSO4, filtered and evaporated giving 2-[4-(2-nitro-vinyl)-phenoxy]-5-trifluoromethyl-pyridine (1.225 mmol, yield=56%, purity=95%). [M+H]+=311.23 1H NMR (300 MHz, DMSO-d6) δ/ppm 7.27-7.36 (m, 3H), 7.91-7.98 (m, 2H), 8.24-8.30 (m, 1H), 8.55-8.62 (m, 1H)
Reaction SMILES: [NH2:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1.[F:11][C:12]([F:19])([F:18])[C:13](OCC)=[O:14]>>[CH2:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10][CH:2]1[NH:1][C:13](=[O:14])[C:12]([F:19])([F:18])[F:11]
Reactant: CCOC(=O)C(F)(F)F
Reactant: NC1Cc2ccccc2C1
Product: O=C(NC1Cc2ccccc2C1)C(F)(F)F

Procedure:
Preferably in Step (i), 2-aminoindan is reacted with ethyl trifluoroacetate to form N-(2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide.