Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].Cl.[CH2:3]([N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Br[CH:19]([CH3:35])[C:20]([C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:33][CH3:34])[C:28]=2[Cl:32])[CH:23]=1)=[O:21].C([O-])([O-])=O.[K+].[K+]>C(Cl)(Cl)Cl>[ClH:32].[ClH:1].[CH2:3]([N:12]1[CH2:17][CH2:16][N:15]([CH:19]([C:20]([C:22]2[CH:31]=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27]([O:33][CH3:34])[C:28]=3[Cl:32])[CH:23]=2)=[O:21])[CH3:35])[CH2:14][CH2:13]1)[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: C(=Cc1ccccc1)CN1CCNCC1
Reactant: COc1ccc2cc(C(=O)C(C)Br)ccc2c1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: COc1ccc2cc(C(=O)C(C)N3CCN(CC=Cc4ccccc4)CC3)ccc2c1Cl
Yield: 437.1 %

Procedure:
A mixture of N-cinnamyl piperazine dihydrochloride (2.75 g, 10 mmol), 2-bromo-1-(5-chloro-6-methoxynaphthalen-2-yl)propan-1-one (1.05 g, 3.2 mmol) and K2CO3 (1.3 g, 9.5 mmol) in 50 ml of CHCl3 was treated according to general preparation 2 to give 3.65 g of compound (IV-35), yield 70%. M+ 449.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH:13]=[C:12]([CH:14]3[C:20]4[N:21]=[C:22]([CH3:24])[O:23][C:19]=4[CH:18]=[CH:17][C:16]4[CH:25]=[C:26]([CH2:29][CH3:30])[CH:27]=[CH:28][C:15]3=4)[C:11](=[O:31])[NH:10][C:9]2=[O:32])[CH:5]=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[CH2:42]([O:44][C:45](=[O:57])[CH2:46][C:47]1[N:48]=[C:49]([NH:52][C:53](=[O:56])[CH2:54][NH2:55])[S:50][CH:51]=1)[CH3:43]>CN1CCCC1=O>[CH2:29]([C:26]1[CH:27]=[CH:28][C:15]2[CH:14]([C:12]3[C:11](=[O:31])[NH:10][C:9](=[O:32])[N:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([NH:55][CH2:54][C:53]([NH:52][C:49]5[S:50][CH:51]=[C:47]([CH2:46][C:45]([O:44][CH2:42][CH3:43])=[O:57])[N:48]=5)=[O:56])[N:7]=4)[CH:13]=3)[C:20]3[N:21]=[C:22]([CH3:24])[O:23][C:19]=3[CH:18]=[CH:17][C:16]=2[CH:25]=1)[CH3:30]
Reactant: CCc1ccc2c(c1)C=Cc1oc(C)nc1C2c1cn(-c2ccnc(Cl)n2)c(=O)[nH]c1=O
Reactant: CCOC(=O)Cc1csc(NC(=O)CN)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: CCOC(=O)Cc1csc(NC(=O)CNc2nccc(-n3cc(C4c5ccc(CC)cc5C=Cc5oc(C)nc54)c(=O)[nH]c3=O)n2)n1
Temperature: 90 °C
Reaction time: 24 h

Procedure:
A mixture of the products from steps (viii) (0.65 g) and (ix) (1.025 g) and N,N-diisopropylethylamine (1.26 ml) in N-methylpyrrolidin-2-one (10 ml) was stirred at 90° C. for 24 hours. A further 0.342 g of product from step (ix) and N,N-diisopropylethylamine (0.5 ml) was added and heating continued for a further 24 hours. The solution was partitioned between 1N hydrochloric acid and ethyl acetate. The organic layer was washed with water, dried (MgSO4) and evaporated to give a brown oil which was purified by chromatography eluting with ethyl acetate.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]=[C:15]=[S:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]1[NH2:24]>C1COCC1>[NH2:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]1[NH:24][C:15]([NH:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[O:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[S:16]
Reactant: N[C@@H]1CCCC[C@H]1N
Reactant: S=C=Nc1ccccc1Oc1ccccc1
Solvent: C1CCOC1
Product: N[C@@H]1CCCC[C@H]1NC(=S)Nc1ccccc1Oc1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 1.6 g of 2-phenoxyphenyl isothiocyanate in 10 ml of THF was added to a solution of 0.8 g of trans-1,2-diaminocyclohexane in 30 ml of THF, and the mixture was stirred at room temperature for about 4 hours. The solvent was evaporated and the residue was subsequently subjected to column chromatography on silica gel using a mixture of 10 parts of ethyl acetate, 5 parts of n-heptane, 5 parts of methylene chloride, 5 parts of methanol and 1 part of concentrated aqueous ammonia solution, giving the desired compound as an amorphous oily product.
Reaction SMILES: [H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[CH:8]1([CH2:11][O:12][C:13]2[C:14]([C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:26](=[O:33])[N:25]([CH3:34])[CH:24]=3)=[N:15][C:16](S(C)(=O)=O)=[N:17][CH:18]=2)[CH2:10][CH2:9]1.C(O)(=O)C>CN(C=O)C>[CH:8]1([CH2:11][O:12][C:13]2[C:14]([C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:26](=[O:33])[N:25]([CH3:34])[CH:24]=3)=[N:15][C:16]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[N:17][CH:18]=2)[CH2:9][CH2:10]1
Reactant: Cn1cc(-c2nc(S(C)(=O)=O)ncc2OCC2CC2)c2ccccc2c1=O
Reactant: CS(N)(=O)=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: Cn1cc(-c2nc(NS(C)(=O)=O)ncc2OCC2CC2)c2ccccc2c1=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 96.2 %

Procedure:
Sodium hydride (0.93 g, 23.37 mmol, 60% in mineral oil) was added to MeSO2NH2 (2.22 g, 23.37 mmol) in dry DMF (30 mL) at 0° C. over 15 min. The mixture was stirred at 0° C. for 1 h and the title compound of step 5 (3.00 g, 7.79 mmol) was added. The mixture was heated at 60° C. for 6 h. After cooling, ice water was added and the pH was adjusted to 5 with acetic acid. The suspended solids were collected and washed with MTBE (50 mL) to afford the title compound (3 g, yield: 96.7%) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 9.80 (s, 1H), 8.53 (d, J=8.0 Hz, 1H), 8.42 (s, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.70 (m, 2H), 7.56 (t, J=7.6 Hz, 1H), 3.87 (d, J=7.2 Hz, 2H), 3.70 (s, 3H), 3.39 (s, 3H), 1.12 (m, 1H), 0.58 (m, 2H), 0.24 (m, 2H). LCMS: 401.1 (M+1)+
Reaction SMILES: [C:1]([CH:5]1[CH2:10][CH2:9][C:8](=[O:11])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH2:12]([Si:15](C)([CH3:17])[CH3:16])C=C.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[C:1]([CH:5]1[CH2:6][CH2:7][C:8]([O:11][Si:15]([CH3:17])([CH3:16])[CH3:12])=[CH:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)C1CCC(=O)CC1
Reactant: C=CC[Si](C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(C)(C)C1CC=C(O[Si](C)(C)C)CC1
Reaction time: 0.08 h
Yield: 88 %

Procedure:
Into a two-necked flask were placed 4-tert-butylcyclohexanone (74.1 mg, 0.480 mmol), and toluene (5.0 ml) as a solvent, and the mixture was subjected to heating under reflux conditions under an argon atmosphere. After the start of the refluxing, allyltrimethylsilane (82.3 mg, 0.720 mmol) was added, and a solution (0.1 M) of triflic imide (1.35 mg, 4.80 μmol) in toluene was added dropwise. After 5 min, triethylamine (0.486 mg, 4.80 μmol) was added, and the mixture was reacted for 10 min. Thereafter, cooled aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with hexane and dried over sodium sulfate. The solvent was evaporated under reduced pressure and purified by column chromatography to give the object product 4-tert-butyl-1-trimethylsilyloxy-1-cyclohexene (yield 88%).
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:15]2[C:14](=[O:18])C3C(=CC=CC=3)[C:7](=[O:19])[C:6]=2[C:5]=1[N+]([O-])=O)([O-:3])=[O:2].[N+:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([O-:25])=[O:24]>>[N+:23]([C:26]1[C:31]2[C:7](=[O:19])[C:6]3[C:15](=[CH:16][CH:17]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[C:14](=[O:18])[C:30]=2[CH:29]=[CH:28][CH:27]=1)([O-:25])=[O:24]
Reactant: O=[N+]([O-])c1ccccc1
Reactant: O=C1c2ccccc2C(=O)c2c1ccc([N+](=O)[O-])c2[N+](=O)[O-]
Product: O=C1c2ccc([N+](=O)[O-])cc2C(=O)c2c1cccc2[N+](=O)[O-]

Procedure:
100 g of a dinitroanthraquinone mixture of the composition A are employed and are stirred with C ml of nitrobenzene at D° C. for B hours, the precipitate is filtered off at D° C. and washed with 50 ml of nitrobenzene and the material on the filter is freed from nitrobenzene in vacuo. E g of 1,7-dinitro-anthraquinone of the composition F are obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([F:19])[C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1.[C:20]([C:22]1[CH:23]=[CH:24][C:25]([C:28](O)=[O:29])=[N:26][CH:27]=1)#[N:21]>>[NH2:16][C:10]1[O:11][CH2:12][C:13]([F:15])([F:14])[C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:28]([C:25]3[CH:24]=[CH:23][C:22]([C:20]#[N:21])=[CH:27][N:26]=3)=[O:29])[CH:3]=[C:4]([F:19])[C:5]=2[F:18])([CH3:17])[N:9]=1
Reactant: N#Cc1ccc(C(=O)O)nc1
Reactant: C[C@]1(c2cc(N)cc(F)c2F)N=C(N)OCC1(F)F
Product: C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)cc(F)c2F)N=C(N)OCC1(F)F

Procedure:
The condensation of (R)-4-(5-amino-2,3-difluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate XI-2) and 5-cyano-pyridine-2-carboxylic acid following procedure I yielded the title compound as a light yellow solid. MS (ISP): m/z=408.3 [M+H]+.
Reaction SMILES: Br[C:2]1[C:3](=[O:15])[N:4]([C@@H:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Br:8])[N:7]=1.Cl.[CH3:17][O:18][C:19]1[CH:20]=[C:21]2[C:25](=[C:26]([CH3:28])[CH:27]=1)[NH:24][CH2:23][CH2:22]2>>[Br:8][C:6]1[N:7]=[C:2]([N:24]2[C:25]3[C:21](=[CH:20][C:19]([O:18][CH3:17])=[CH:27][C:26]=3[CH3:28])[CH2:22][CH2:23]2)[C:3](=[O:15])[N:4]([C@@H:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=1
Reactant: COc1cc(C)c2c(c1)CCN2
Reactant: CC[C@H](COC)n1cc(Br)nc(Br)c1=O
Agent: Cl
Product: CC[C@H](COC)n1cc(Br)nc(N2CCc3cc(OC)cc(C)c32)c1=O

Procedure:
Prepared in a similar fashion as described for Example 413 using 3,5-dibromo-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone and 5-methoxy-7-methylindoline hydrochloride as the starting materials. mp 116-118° C.; 1H NMR (300 MHz, CDCl3): δ 6.98 (s, 1 H), 6.67 (s, 1 H), 6.58 (d, J=2.2 Hz, 1 H), 4.97-4.95 (m, 1 H), 4.38 (t, J=7.9 Hz, 2 H), 3.79 (s, 3 H), 3.66 (dd, J=10.6, 5.9 Hz, 1 H), 3.56 (dd, J=10.6, 3.6 Hz, 1 H), 3.36 (s, 3 H), 3.04 (t, J=7.9 Hz, 2 H), 2.06 (s, 3 H), 1.92-1.72 (m, 2 H), 0.94 (t, J=7.5 Hz, 3 H); HRMS (ESI) calcd for C19H25N3O3Br (M+H)+: 422.1079; found m/z 422.1097.
Reaction SMILES: [Na].[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[C:11]#[N:12])[CH:6]=[CH:7][CH:8]=1.Cl.[NH2:20][C:21]([NH2:23])=[NH:22]>C(O)C>[F:2][C:3]1[CH:4]=[C:5]([C:9]2[N:20]=[C:21]([NH2:23])[N:22]=[C:11]([NH2:12])[C:10]=2[C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: N#CC(=Cc1cccc(F)c1)c1ccncc1
Reactant: N=C(N)N
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: Nc1nc(N)c(-c2ccncc2)c(-c2cccc(F)c2)n1

Procedure:
After sodium (6.2 g, 268 mmol) was dissolved in ethanol (700 mL), 3-(3-fluorophenyl)-2-(4-pyridyl)-2-propene nitrile (50 g, 223 mmol) and guanidine hydrochloride (25.6 g, 268 mmol) were added thereto in this order and heated under reflux for 4 hours. After cooling as it was, the solvent was removed. Tetrahydrofuran (500 mL) was added to the residue, the insoluble matters were filtered off, and the filtrate was concentrated. A suspension of the residues and activated manganese dioxide (200 g) in chloroform (1000 mL) was heated under reflux for 2 hours. After cooling as it was, the manganese dioxide was filtered off through Celite, and washed with tetrahydrofuran (500 mL33 3) and methanol-chloroform (1:1) (1000 mL×2). The collected filtrate was concentrated, and then methanol was added to the residue. The resulting precipitates were collected by filtration, to give the title compound as a crude solid (14.6 g). The crude crystals were recrystallized from methanol-chloroform, to give the title compound (12.4 g, 20%) as a colorless solid.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([OH:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:30][C:31](=[O:43])[C:32]([C:35]1[CH:40]=[CH:39][C:38]([CH2:41]Br)=[CH:37][CH:36]=1)([CH3:34])[CH3:33]>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=1)[O:24][CH2:41][C:38]1[CH:37]=[CH:36][C:35]([C:32]([CH3:34])([CH3:33])[C:31]([OH:43])=[O:30])=[CH:40][CH:39]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)C(C)(C)c1ccc(CBr)cc1
Reactant: Oc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Product: CC(C)(C(=O)O)c1ccc(COc2cccc(-c3c(Cc4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc1

Procedure:
Prepared using the procedure in Example 56 except using 3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenol and 2-(4-Bromomethyl-phenyl)-2-methyl-propionic acid methyl ester as the halide. MS (ESI) m/z 556.
Reaction SMILES: [NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3][C:4](O)=[O:5].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1.CCOCC>[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3][CH2:4][OH:5]
Reactant: NC(CC(=O)O)c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: NC(CCO)c1ccccc1
Temperature: 0 °C
Reaction time: 24 h

Procedure:
To a suspension of 3-amino-3-phenylpropanoic acid (2.0 g, 12.1 mmol) in dry THF (45 mL) cooled to 0° C. under N2 was added portionwise over 20 minutes solid LiAlH4 (920 mg, 24.2 mmol). Stirring was continued at room temperature for 24 h. after which time solid Na2SO4.10H2O was added with stirring until only a heavy white precipitate was present. The organic layer was diluted with ether and filtered through Celite® and the concentrated in vacuo. The residue was dissolved in ethyl acetate (50 mL) and extracted with 1N HCl (3×40 mL). The aqueous layers were combined and basified to pH ˜12 with 5M NaOH. The aqueous phase was extracted with ethyl acetate (3×50 mL) and the combined organic phases dried (Na2SO4) and concentrated in vacuo to separate the product which was used without further purification (0.9 g, 49%).
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])C=C.B(Cl)(Cl)Cl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[C:15]([C:13]1[CH:12]=[C:7]([CH:6]=[C:5]([OH:4])[CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])#[N:16]
Reactant: C=CCOc1cc(C#N)cc(C(=O)OC)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: ClB(Cl)Cl
Agent: [I-]
Solvent: ClCCl
Product: COC(=O)c1cc(O)cc(C#N)c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 66.3 %

Procedure:
A mixture of methyl 3-allyloxy-5-cyanobenzoate (1.5 g, 6.9 mmol) and tetrabutylammonium iodide (2.8 g, 7.6 mmol) in dichloromethane (38 mL) at −78° C., under argon, was treated with a solution of 1M boron trichloride in dichloromethane (24 mL, 24 mmol). After 5 minutes at −78° C., the reaction mixture was stirred at ambient temperature for 1 hour. The reaction was then quenched with ice water and stirred for an additional 30 minutes. The organic layer was washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated. Silica gel chromatography using a gradient of 20–30% ethyl acetate/hexanes afforded 811 mg (67%) of methyl 3-cyano-5-hydroxybenzoate as a light yellow solid.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=2.Br[CH2:18][C:19](=[CH2:24])[C:20]([O:22][CH3:23])=[O:21]>>[C:15]([C:7]1[C:8]([C:11]([F:12])([F:14])[F:13])=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]([CH2:24][C:19](=[CH2:18])[C:20]([O:22][CH3:23])=[O:21])[C:2]([CH3:1])=[CH:10]2)#[N:16]
Reactant: Cc1cc2c(C(F)(F)F)c(C#N)ccc2[nH]1
Reactant: C=C(CBr)C(=O)OC
Product: C=C(Cn1c(C)cc2c(C(F)(F)F)c(C#N)ccc21)C(=O)OC

Procedure:
Synthesized as described in Example 4 using 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 120) and methyl 2-(bromomethyl)-2-propenoate: 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J=8.4 Hz, 1H), 7.38 (d, J=8.4 Hz, 1H), 6.63 (s, 1H), 6.23 (s, 1H), 4.99, (s, 2H), 4.81 (s, 1H), 3.84 (s, 3H), 2.43 (s, 3H); MS (ES) m/z 323 (M+1).
Reaction SMILES: Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[CH:16][N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[NH2:24][C:25]1([CH2:29][OH:30])[CH2:28][NH:27][CH2:26]1>>[NH2:24][C:25]1([CH2:29][OH:30])[CH2:28][N:27]([C:2]2[CH:23]=[CH:22][C:5]3[C:6]4[N:7]([CH:11]=[C:12]([C:14]5[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[CH:16][N:15]=5)[N:13]=4)[CH2:8][CH2:9][O:10][C:4]=3[CH:3]=2)[CH2:26]1
Reactant: NC1(CO)CNC1
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc(Br)cc1OCC2
Product: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc(N3CC(N)(CO)C3)cc1OCC2

Procedure:
Following the procedures of Example 551, 9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 194 and (3-aminoazetidin-3-yl)methanol were reacted to give 525. LC/MS (ESI+): m/z 396.2 (M+H)
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Br[CH2:11][CH2:12][CH2:13][Cl:14]>>[Cl:14][CH2:13][CH2:12][CH2:11][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: c1ccc2[nH]ccc2c1
Reactant: ClCCCBr
Product: ClCCCn1ccc2ccccc21

Procedure:
Prepared by Procedure AH, and Scheme P using 1H-indole and 1-bromo-3-chloropropane: 1H NMR (400 MHz, CDCl3) δ 7.70-7.04 (m, 5H), 6.50 (d, 1H, J=2.8 Hz), 4.31 (t, 2H, J=6.8 Hz), 3.42 (t, 2H, J=6.4 Hz), 2.28-2.20 (m, 2H).
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[C:11]([NH2:15])(=[O:14])[CH:12]=[CH2:13].S(=O)(=O)(O)O>>[S:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[S:1][CH:12]([CH3:13])[C:11]([NH2:15])=[O:14]
Reactant: Sc1nc2ccccc2s1
Reactant: C=CC(N)=O
Agent: O=S(=O)(O)O
Product: CC(Sc1nc2ccccc2s1)C(N)=O
Temperature: 0 °C

Procedure:
A finely powdered mixture of 16.8 g of 2-mercaptobenzothiazole and 7.5 g of acrylic amide is added at 45°-50° in the course of 1 hour to 100 ml 70% sulfuric acid, with stirring. After a further hour at 45°-50°, the rection mixture is poured into ice water. The precipitate is filtered off, washed with water and dried. The obtained 2-(benzthiazol-2-ylthio)-propionic acid amide is recrystallized from ethylacetate and melts at 144°-145°.
Reaction SMILES: [OH:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:13]([O:15][CH3:16])=[O:14])[NH:6]2.[C:17](OC(=O)C)(=[O:19])[CH3:18]>CN(C1C=CN=CC=1)C>[C:17]([O:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:13]([O:15][CH3:16])=[O:14])[NH:6]2)(=[O:19])[CH3:18]
Reactant: COC(=O)c1cc2c(O)c(OC)ccc2[nH]1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Product: COC(=O)c1cc2c(OC(C)=O)c(OC)ccc2[nH]1
Yield: 75 %

Procedure:
A stirred solution of methyl 4-hydroxy-5-methoxyindole-2-carboxylate (0.51 g) and DMAP (10 mg) in acetic anhydride (5 ml) was heated at 80° C. for 4 hours. The reaction was concentrated in vacuo and the residue dissolved in dichloromethane and washed with hydrochloric acid (2.0 M), saturated aqueous sodium hydrogen carbonate solution, water, aqueous saturated sodium chloride solution and dried (MgSO4). The solution was concentrated in vacuo and the residue was purified by column chromatography using 50% diethyl ether:iso-hexane as eluent to give the product as a white solid (0.58 g, 75%), NMR d CD3SOCD3) 2.34 (s, 3H), 3.75 (s, 3H), 3.85 (s, 3H), 6.99 (d, 1H), 7.19 (d, 1H), 7.29 (d, 1H), 11.93 (brs, 1H); M/z (+) 264 (MH+).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH2:20][CH3:21])[CH:13]=1)[OH:11].[Mn]([O-])(=O)(=O)=O.[Ba+2].[Mn]([O-])(=O)(=O)=O>C(#N)C>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH2:20][CH3:21])[CH:13]=1)=[O:11]
Reactant: CCCOc1cccc(C(O)c2nc3ccccc3s2)c1
Agent: O=[Mn](=O)(=O)[O-]
Agent: [Ba+2]
Solvent: CC#N
Product: CCCOc1cccc(C(=O)c2nc3ccccc3s2)c1

Procedure:
A mixture benzothiazol-2-yl(3-propoxyphenyl)methanol (1 g) and barium permanganate (0.95 g) in acetonitrile 15 mL) is refluxed for 30 minutes. The mixture is filtered over a clarcel pad, concentrated under reduced pressure and purified by column chromatography over silica gel (eluant heptane/ethyl acetate: 4/1) to give benzothiazol-2-yl(3-propoxyphenyl)methanone as a white crystalline solid.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1.[B-](F)(F)(F)F.CN(C(O[N:25]1[C:30](=O)[CH:29]=[CH:28]C=C1)=[N+](C)C)C.CCN(C(C)C)C(C)C.C1(N)CC1>CN(C=O)C>[CH:30]1([NH:25][C:9]([C:6]2[CH:5]=[CH:4][C:3]([CH2:2][OH:1])=[CH:8][N:7]=2)=[O:11])[CH2:28][CH2:29]1
Reactant: O=C(O)c1ccc(CO)cn1
Reactant: CN(C)C(On1ccccc1=O)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: NC1CC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC1CC1)c1ccc(CO)cn1

Procedure:
5-Hydroxymethyl-pyridine-2-carboxylic acid (0.23 g, 1.5 mmol) was dissolved in DMF (3 ml) and activated with TPTU (0.45 g, 1.5 mmol), Hünig's base (0.51 ml, 3.0 mmol) and reacted with cyclopropyl amine (0.12 ml, 1.65 mmol) for 1 h at r.t during which a precipitate was formed. Solvent was removed and the residue dissolved in acetonitrile/water and purified by prep.RP(C18)HPLC: 60 mg;
Reaction SMILES: [Na].O.S(O)(O)(=O)=O.[OH:8][NH:9][C:10]([NH2:12])=[NH:11].O[NH:14]C(N)=N.O.C(NC(=O)/C=C(\[O:28][C:29]([C:31]1[C:36](N)=[N:35][C:34]([NH2:38])=[C:33]([Cl:39])[N:32]=1)=O)/C)(C)(C)C>CC(O)C>[NH2:14][NH:11][C:10](=[NH:12])[NH:9][O:8][C:29]([C:31]1[CH:36]=[N:35][C:34]([NH2:38])=[C:33]([Cl:39])[N:32]=1)=[O:28]
Reactant: C/C(=C/C(=O)NC(C)(C)C)OC(=O)c1nc(Cl)c(N)nc1N
Reactant: N=C(N)NO
Agent: O=S(=O)(O)O
Agent: [Na]
Solvent: CC(C)O
Solvent: O
Product: N=C(NN)NOC(=O)c1cnc(N)c(Cl)n1

Procedure:
Sodium metal (3.1 g., 0.135 g.at.) is dissolved in 2-propanol (500 ml.) and hydroxyguanidine hemisulfate hydrate (20.0 g., 0.075 mole) is added. The reaction mixture is heated at reflux for 1 hour then treated with N-t-butyl-3-(3,5-diamino-6-chloropyrazinecarbonyloxy)-crotonamide (20.5 g., 0.06 mole) heated at reflux for an additional hour to give product which is filtered, washed with water and dried. 3,5-Diamino-6-chloropyrazinecarbonyloxyguanidine melts at 192°-3° C. after purification by precipitation from dilute aqueous methanesulfonic acid with aqueous ammonia.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: OCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: OCCCCCOc1ccc(Br)cc1
Temperature: 52.5 °C
Reaction time: 5 h
Yield: 76.4 %

Procedure:
In a flask equipped with a stirrer and a thermometer, 4.29 g (24.8 mmol) of 4-bromophenol was dissolved in 40 ml of dry dimethylformamide (abbreviated as DMF hereinbelow) under a nitrogen atmosphere, and 5.0 g (29.9 mmol) of 5-bromopentanol and 4.14 g (29.9 mmol) of potassium carbonate were added at room temperature, followed by stirring at 50 to 55° C. for 5 hours under incubation. After the completion of the reaction, water was added, and the mixture was subjected to extraction with ethyl acetate. The resulting organic phase was washed with NaCl saturated water, dried over anhydrous sodium sulfate, filtered, and concentrated, to thereby obtain 7.8 g of a crude product in the form of a yellow oil. The crude product was then purified by silica gel column chromatography using hexane/ethyl acetate as an eluting solvent to obtain 4.91 g of 5-(4-bromophenoxy)pentanol in the form of a light yellow oil in a 76% yield.