Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:5]1[C:6](=[CH:32][CH:33]=O)[CH2:7][C:8]([CH3:31])([CH3:30])[CH2:9][C:10]=1[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH2:22][CH3:23])=[CH:15][C:14]=1[O:28][CH3:29])[CH2:2][CH2:3][CH3:4].[C:35]([C:37]1[C:38](=[C:53]([C:56]#[N:57])[C:54]#[N:55])[O:39][C:40]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:43]([F:46])([F:45])[F:44])[C:41]=1[CH3:42])#[N:36]>>[CH2:1]([C:5]1[C:6](=[CH:32][CH:33]=[CH:42][C:41]2[C:40]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:43]([F:46])([F:44])[F:45])[O:39][C:38](=[C:53]([C:56]#[N:57])[C:54]#[N:55])[C:37]=2[C:35]#[N:36])[CH2:7][C:8]([CH3:30])([CH3:31])[CH2:9][C:10]=1[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH2:22][CH3:23])=[CH:15][C:14]=1[O:28][CH3:29])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC1=C(C=Cc2ccc(N(CCCC)CCCC)cc2OC)CC(C)(C)CC1=CC=O
Reactant: CC1=C(C#N)C(=C(C#N)C#N)OC1(c1ccccc1)C(F)(F)F
Product: CCCCC1=C(C=Cc2ccc(N(CCCC)CCCC)cc2OC)CC(C)(C)CC1=CC=CC1=C(C#N)C(=C(C#N)C#N)OC1(c1ccccc1)C(F)(F)F
Temperature: 50 °C
Yield: 69.7 %

Procedure:
118 mg (0.25 mmol) of [2-butyl-3-[2-(4-dibutylamino-2-methoxyphenyl)vinyl]-5,5-dimethyl-2-cyclohexenylidene]acetaldehyde and 90 mg (0.29 mmol) of 2-(3-cyano-4-methyl-5-phenyl-5-trifluoromethyl-2(5H)-furanylidene]propanedinitrile were dissolved, and the mixture was stirred with heating at 50° C. for 40 minutes. The solvent was evaporated off. The residue was purified by silica gel column chromatography and washed with methanol to give 133 mg of a black crystal having a mp of 109-113° C. (yield: 68.9%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH:10][C:11](=[O:27])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:13]=1.[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](OC(C(F)(F)F)C(F)(F)F)(=[O:37])=[O:36])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>C(OCC)(=O)C.CN(C)C=O>[Br:1][C:2]1[CH:7]=[C:6]([O:8][S:35]([C:32]2[CH:33]=[CH:34][C:29]([CH3:28])=[CH:30][CH:31]=2)(=[O:37])=[O:36])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH:10][C:11](=[O:27])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][C:19](=[O:26])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:13]=1
Reactant: Cc1cc(O)cc(Br)c1NC(=O)c1cccc(NC(=O)c2ccccc2)c1
Reactant: Cc1ccc(S(=O)(=O)OC(C(F)(F)F)C(F)(F)F)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)Oc2cc(C)c(NC(=O)c3cccc(NC(=O)c4ccccc4)c3)c(Br)c2)cc1
Temperature: 70 °C
Reaction time: 6 h
Yield: 12.2 %

Procedure:
0.30 g of N-(2-bromo-6-methyl-4-hydroxyphenyl) 3-(benzoylamino)benzamide, 0.23 g of 1,1,1,3,3,3-hexafluoroisopropyl p-toluenesulfonate, 0.19 g of potassium carbonate and 0.03 g of 18-crown-6 ether were added to 5 ml of N,N-dimethylformamide, and the resulting mixture was stirred at 70° C. for 6 hours. 100 ml of ethyl acetate was added thereto and washed with water (50 ml×2). The organic phase was dried over anhydrous magnesium sulfate and the solvent was removed under a reduced pressure to obtain a residue. The resulting residue was purified by silica gel column chromatography (n-hexane EtOAc=3:1) to obtain 0.05 g of the desired product (Yield: 13%).
Reaction SMILES: [CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].C([Li])CCC.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2([C:22]#[N:23])[CH2:21][CH2:20][CH2:19]2)=[CH:14][CH:13]=1.O>O1CCCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2([C:22]([NH2:23])=[CH:1][S:2]([CH3:5])(=[O:4])=[O:3])[CH2:21][CH2:20][CH2:19]2)=[CH:16][CH:17]=1
Reactant: N#CC1(c2ccc(Cl)cc2)CCC1
Reactant: CS(C)(=O)=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: CS(=O)(=O)C=C(N)C1(c2ccc(Cl)cc2)CCC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of dimethylsulphone (8.3 g), in dry tetrahydrofuran (150 ml) was added dropwise to a stirred ice-cold solution of butyllithium (30 ml of 2.6M solution in hexane). The mixture was stirred at room temperature for 15 minutes and then a solution of 1-(4-chlorophenyl)cyclobutanecarbonitrile (15 g) in tetrahydrofuran (25 ml) was added over 15 minutes and the resulting solution was heated under reflux for 16 hours. The solution was cooled and treated with water and the organic layer separated. The aqueous layer was extracted with ether and the ether extracts combined with the previously separated organic layer, dried and the solvents were removed by evaporation. The resulting oil crystallised, and the solid was washed with petroleum ether (b.p. 40°-60° C.) to give 1-[1-(4-chlorophenyl)cyclobutyl]-2-methylsulphonylvinylamine (m.p. 125°-126° ).
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:18][OH:19]>>[N:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C:13](=[N:18][OH:19])[CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1CCN(CCCN2CCCCC2)CC1
Reactant: NO
Agent: Cl
Product: ON=C1CCN(CCCN2CCCCC2)CC1

Procedure:
1-(3-(1-Piperidinyl)propyl)-4-piperidone oxime is prepared from 1-(3-(1-piperidinyl)propyl)-4-piperidone and hydroxylamine hydrochloride essentially as described above in Example 38, Scheme C, step b.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[C:8]([C:14](=O)/[CH:15]=[CH:16]/N(C)C)=[CH:9][N:10]([CH2:11][CH2:12][CH3:13])[C:5]2=[C:4]([CH3:21])[CH:3]=1.Cl.[NH:23]([C:27]1[CH:28]=[C:29]([S:33]([NH2:36])(=[O:35])=[O:34])[CH:30]=[CH:31][CH:32]=1)[C:24]([NH2:26])=[NH:25].[OH-].[Na+]>COCCO>[Cl:1][C:2]1[N:7]=[C:6]2[C:8]([C:14]3[CH:15]=[CH:16][N:26]=[C:24]([NH:23][C:27]4[CH:28]=[C:29]([S:33]([NH2:36])(=[O:34])=[O:35])[CH:30]=[CH:31][CH:32]=4)[N:25]=3)=[CH:9][N:10]([CH2:11][CH2:12][CH3:13])[C:5]2=[C:4]([CH3:21])[CH:3]=1
Reactant: N=C(N)Nc1cccc(S(N)(=O)=O)c1
Reactant: CCCn1cc(C(=O)/C=C/N(C)C)c2nc(Cl)cc(C)c21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: COCCO
Product: CCCn1cc(-c2ccnc(Nc3cccc(S(N)(=O)=O)c3)n2)c2nc(Cl)cc(C)c21
Temperature: 150 °C

Procedure:
A mixture of (E)-1-(5-chloro-7-methyl-1-propyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-3-(dimethylamino)prop-2-en-1-one (0.2 mmol), 3-guanidinobenzenesulfonamide hydrochloride (0.5 mmol) and NaOH (0.8 mmol) in 3 mL of 2-methoxyethanol was heated in a Microwave at 150° C. for 30 minutes. The reaction mixture was purified by column chromatography using EtOAc/PE (1:1, v/v) to elute 3-(4-(5-chloro-7-methyl-1-propyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyrimidin-2-ylamino)benzenesulfonamide which was re-crystallised from EtOAc to give white solid. 1H-NMR (DMSO-d6) δ: 0.92 (t, 3H, J=7.2 Hz, CH3), 1.87 (m, 2H, CH2), 4.42 (t, 2H, J=7.2 Hz, CH2), 7.19 (s, 1H, Ar—H or Ph-H), 7.34 (s, 2H, NH2), 7.43 (m, 1H, Ar—H or Ph-H), 7.49 (t, 1H, J=7.6 Hz, Ph-H), 7.62 (m, 1H, Ph-H), 8.02 (d, 1H, J=4.8 Hz, Pyrimidin-H), 8.55 (d, 1H J=5.2 Hz, Pyrimidin-H), 8.63 (s, 1H, Ar—H), 9.92 (s, 1H, NH). MS (ESI+) m/z 457.1245 (M+H)+.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][N:4]([S:7]([NH:10]C(=O)OCC2C=CC=CC=2)(=[O:9])=[O:8])[CH2:3]1>[C].[Pd].CO>[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([S:7]([NH2:10])(=[O:9])=[O:8])[CH2:3]1
Reactant: O=C(NS(=O)(=O)N1CCC(O)C1)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: NS(=O)(=O)N1CCC(O)C1
Reaction time: 3 h
Yield: 99.2 %

Procedure:
Benzyl [(3-hydroxypyrrolidin-1-yl)sulfonyl]carbamate (2.55 g) was added to MeOH, and subsequently, 10% palladium carbon (657 mg, 55% wet) was added thereto, followed by stirring at a normal temperature/a normal pressure for about 3 hours under a hydrogen atmosphere. The catalyst was collected by filtration through Celite, and the filtrate was concentrated under reduced pressure to obtain 3-hydroxypyrrolidin-1-sulfonamide (1.4 g) as a colorless oily substance.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:11])[C:9]=1[OH:10])[C:5]#[N:6].[CH3:12][C:13]1([CH3:20])[O:17][CH:16]([CH2:18]O)[CH2:15][O:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.C1(C)C=CC=CC=1>[CH3:12][C:13]1([CH3:20])[O:17][CH:16]([CH2:18][O:10][C:9]2[C:8]([CH3:11])=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=2[CH3:1])[CH2:15][O:14]1
Reactant: Cc1cc(C#N)cc(C)c1O
Reactant: CC1(C)OCC(CO)O1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: Cc1cc(C#N)cc(C)c1OCC1COC(C)(C)O1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
To a solution of 3,5-dimethyl-4-hydroxy-benzonitrile (5.0 g, 34.0 mmol) in THF (40 mL), rac-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (4.49 g, 34.0 mmol) followed by triphenylphosphine (13.4 g, 50.9 mmol) is added. The mixture is cooled with an ice-bath before DEAD (8.87 g, 50.9 mmol, 23.4 mL of a 40% solution in toluene) is added dropwise. The mixture is stirred at rt for 1 h, the solvent is removed in vacuo and the residue is purified by CC on silica gel eluting with heptane:EA 99:1 to 92:8 to give rac-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,5-dimethyl-benzonitrile (7.20 g) as a pale yellow oil; LC-MS: tR=0.99 min, [M+1]+=not detected. b) To a solution of potassium tert.-butylate (6.18 g, 55.1 mmol) in methanol (125 mL), hydroxylamine hydrochloride (5.74 g, 82.7 mmol) is added. To this solution, a solution of rac-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,5-dimethyl-benzonitrile (7.20 g, 27.6 mmol) in methanol (40 mL) is added. The mixture is refluxed for 72 h before the solvent is removed in vacuo. The residue is purified by prep. HPLC (XBridge Prep C18, 30×75 mm, 5 μm, 2-95% acetonitrile in water containing 0.5% sat. aq. NH3) to give the title compound (4.85 g) as a pale yellow solid; LC-MS: tR=0.67 min, [M+1]+=295.06; 1H NMR (CDCl3): δ1.43 (s, 3H), 1.48 (s, 3H), 2.29 (s, 6H), 3.76-3.81 (m, 1H), 3.83-3.88 (m, 1H), 3.93-3.99 (m, 1H), 4.17-4.23 (m, 1H), 4.47-4.54 (m, 1H), 5.02 (s br, 1H), 7.28 (s, 2H).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:17])=[O:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][CH:31]=1>C(COC)OC.C(OC(=O)C)C>[CH2:1]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:34]([C:33]3[CH:36]=[CH:37][C:30]([Cl:29])=[CH:31][CH:32]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[S:15]2(=[O:17])=[O:16])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: O=S(=O)(NC1CCN(Cc2ccccc2)CC1)c1ccccc1
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: O=S1(=O)c2ccccc2C(c2ccc(Cl)cc2)N1C1CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Yield: 65.7 %

Procedure:
To a solution of 19.16 g (58.1 mmol) of N-(1-benzylpiperidin-4-yl)-benzene sulfonamide in 300 mL of dimethoxyethane at 0° C. was added 46.4 mL (116.1 mmol) of a n-butyllithium (2.5 M) slowly via addition funnel. The mixture was stirred using an overhead stirrer for 45 minutes at 0° C., then 9.61 g (63.9 mmol) of p-chlorobenzaldehyde was added in one portion. The mixture was allowed to warm to room temperature, diluted with 1 liter of ethylacetate and washed 2×500 mL of water followed by 500 mL of brine. The organic phase was separated, dried (MgSO4), and concentrated in vacuo. The residue was flash chromatographed over 300 g of silica gel (eluted with ethylacetate:heptane-2:1) to afford 17.3 g of product as an orange paste.
Reaction SMILES: F[C:2]1[N:9]=[CH:8][CH:7]=[C:6]([I:10])[C:3]=1[C:4]#[N:5].O.[NH2:12][NH2:13]>CO>[NH:12]([C:2]1[N:9]=[CH:8][CH:7]=[C:6]([I:10])[C:3]=1[C:4]#[N:5])[NH2:13]
Reactant: N#Cc1c(I)ccnc1F
Reactant: NN
Solvent: O
Solvent: CO
Product: N#Cc1c(I)ccnc1NN
Temperature: 20 °C
Reaction time: 0.33 h

Procedure:
To a solution of 1.2 g of 2-fluoro-4-iodonicotinonitrile in 20 mL of MeOH at 20° C. are added 2.4 mL of hydrazine hydrate. The yellow suspension is stirred for 20 minutes at 20° C. and is then filtered. The precipitate is washed with methanol to give, after drying under vacuum, 947 mg of a white powder of 2-hydrazino-4-iodonicotinonitrile.
Reaction SMILES: C([O:3][C:4](=[O:27])[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][C:6]=1[CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:20][CH:19]=2)[CH2:14][CH2:13]1)C.Cl.Cl[CH2:30][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1>>[N:33]1[CH:34]=[CH:35][CH:36]=[C:31]([CH2:30][N:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:18]([CH:15]3[CH2:14][CH2:13][N:12]([CH2:11][C:6]4[N:7]=[CH:8][CH:9]=[CH:10][C:5]=4[C:4]([OH:3])=[O:27])[CH2:17][CH2:16]3)=[CH:19]2)[CH:32]=1
Reactant: CCOC(=O)c1cccnc1CN1CCC(c2c[nH]c3ccccc23)CC1
Reactant: ClCc1cccnc1
Agent: Cl
Product: O=C(O)c1cccnc1CN1CCC(c2cn(Cc3cccnc3)c3ccccc23)CC1

Procedure:
This compound was prepared following the procedure described in example 1 (part E) starting with 0.76 g (0.21 mmol) of 2-[4-(1H-indol-3-yl)-piperidin-1-ylmethyl]-nicotinic acid ethyl ester and 0.04 g (0.25 mmol) of 3-chloromethyl-pyridine hydrochloride. After standard purification, 0.040 g (45% of yield) of the expected acid were obtained.
Reaction SMILES: [C:1]([N:5]([C:7](=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[C:17]1([CH3:26])[CH:22]=[CH:21][CH:20]=[C:19]([C:23](Cl)=[O:24])[CH:18]=1>C1(C)C=CC=CC=1>[C:1]([N:5]([C:7](=[O:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[NH:6][C:23]([C:19]1[CH:18]=[C:17]([CH3:26])[CH:22]=[CH:21][CH:20]=1)=[O:24])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cccc(C(=O)Cl)c1
Reactant: CC(C)(C)N(N)C(=O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: Cc1cccc(C(=O)NN(C(=O)c2ccccc2)C(C)(C)C)c1
Reaction time: 2 h

Procedure:
To a stirred mixture of N'-t-butyl-N'-benzoylhydrazine (1.0 g) in 15 ml toluene and aqueous sodium hydroxide (0.5 g of 50% NaOH) was added 3-toluoylchloride (0.9 g). After stirring for 2 hours, the product was isolated by filtration to give N'-t-butyl-N-(3-toluoyl)-N'-benzoylhydrazine in good yield. m.p. 111-114° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][S:14]([NH2:17])(=[O:16])=[O:15])[CH2:8][CH2:7]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:43][C:44]1[CH:52]=[CH:51][CH:50]=[CH:49][C:45]=1[C:46](O)=[O:47]>CN(C1C=CN=CC=1)C.ClCCl>[Cl:43][C:44]1[CH:52]=[CH:51][CH:50]=[CH:49][C:45]=1[C:46]([NH:17][S:14]([CH2:13][CH2:12][N:9]1[CH2:10][CH2:11][CH:6]([O:5][C:4]2[CH:18]=[CH:19][C:20]([Cl:21])=[C:2]([Cl:1])[CH:3]=2)[CH2:7][CH2:8]1)(=[O:15])=[O:16])=[O:47]
Reactant: O=C(O)c1ccccc1Cl
Reactant: NS(=O)(=O)CCN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: O=C(NS(=O)(=O)CCN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1)c1ccccc1Cl
Reaction time: 17 h
Yield: 28.7 %

Procedure:
4-(3,4-Dichlorophenoxy)-1-piperidineethanesulfonamide (0.1 g), EDCI (0.108 g), HOBT (40 mg), DMAP (40 mg) and 2-chlorobenzoic acid (88 mg) were dissolved in dichloromethane (5 mL) and triethyalamine (0.5 mL) was added. The reaction mixture was stirred for 17 h. The solvents were evaporated. The residue was purified by HPLC (gradient Ammonium acetate/Acetonitrile 95% to 25%; Xterra column) to give the subtitle compound (40 mg)
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=2)[O:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][NH:16][C:17](=[O:23])[CH2:18][S:19][CH2:20][CH2:21][NH2:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:27]([O:29][C:30](Cl)=[O:31])[CH3:28].[Cl-].[Na+]>N1C=CC=CC=1>[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=2)[O:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][NH:16][C:17](=[O:23])[CH2:18][S:19][CH2:20][CH2:21][NH:22][C:30]([O:29][CH2:27][CH3:28])=[O:31])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NCCSCC(=O)NC/C=C\COc1cccc(CN2CCCCC2)c1
Reactant: CCOC(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: c1ccncc1
Product: CCOC(=O)NCCSCC(=O)NC/C=C\COc1cccc(CN2CCCCC2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 24.7 %

Procedure:
There was dissolved 2.7 g (0.0072 mol) of N-[4-[3-(piperidinomethyl) phenoxy]-cis-2-butenyl]-2-(2-aminoethylthio)acetamide in 20 ml of pyridine and added dropwise 0.78 g (0.0072 mol) of ethylchlorocarbonate under cooling with ice, and the mixture was stirred for 18 hours at room temperature. The obtained reaction mixture was poured into ice water and saturated with sodium chloride. The deposited oily matter was extracted with chloroform and washed with saturated aqueous solution of sodium chloride, and then dried over Glauber's salt. Then the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to give 0.8 g of the titled compound as oily matter.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[CH3:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21](=[O:24])[CH2:22]Cl.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O>[CH3:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21](=[O:24])[CH2:22][N:10]1[CH2:9][CH2:8][N:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:12][CH2:11]1
Reactant: c1ccc(N2CCNCC2)nc1
Reactant: Cc1ccccc1NC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccccc1NC(=O)CN1CCN(c2ccccn2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 62.9 %

Procedure:
A mixture of 1-pyridin-2-ylpiperazine (24 mg, 0.15 mmol, Aldrich), N-(2-methyl-phenyl)-2-chloroacetamide (37 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N,N-dimethylformamide/water (2:1, 2 mL) was shaken at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure and the residue purified by preparative HPLC to provide 29.3 mg (63%) of the desired product. 1H NMR (500 MHz, DMSO-d6) δ 2.23 (s, 3H), 2.62 (t, J=4 Hz, 4H), 3.20 (s, 2H), 3.58 (t, J=4 Hz, 4H), 6.63 (t, J=5 Hz, 1H), 6.83 (d, J=6 Hz, 1H), 7.05 (t, J=6 Hz, 1H), 7.10 (m, 2H), 7.58 (t, J=5 Hz, 1H), 7.78 (d, J=6 Hz, 1H), 8.12 (d, J=5 Hz, 1H), 9.40 (s, 1H); MS (ESI/APCI+) m/e 311 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.Br[C:8]1[CH:13]=[CH:12][C:11]([O:14]C)=[CH:10][CH:9]=1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[CH3:1][C:2]1[N:3]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH:4]=[CH:5][N:6]=1
Reactant: Cc1ncc[nH]1
Reactant: COc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: Cc1nccn1-c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.6 %

Procedure:
To a 3-neck, 1-liter, round-bottom flask was added 2-methylimidazole (41.0 g, 0.50 mole), 4-bromoanisole (100 g, 0.53 mole) and potassium carbonate (96.0 g, 0.70 mole) in N-methyl-2-pyrrolidinone (300 ml). A small amount of cuprous chloride (2.5 g) was added. The stirred reaction mixture was heated at reflux temperature for 24 hr and then the N-methyl-2-pyrrolidinone and excess bromoanisole gently distilled. The black pot residue was partitioned between toluene and water and a black solid removed by filtration. The toluene layer was extracted with 48% hydrobromic acid (2×200 ml) and the hydrobromic acid solution was heated at reflux temperature 3 hr then stirred at room temperature overnight. The solution was then concentrated, diluted with water (500 ml) and made basic with sodium hydroxide and sodium bicarbonate solutions. The white solid which precipitated was collected and dried and a small amount recrystallized from methanol/isopropyl alcohol. The total yield was 24.88 g (28.6% yield), mp 205°-208° C.
Reaction SMILES: [CH3:1][N:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[S:3]([C:6]1[CH:25]=[CH:24][C:9]2[N:10]([CH3:23])[C:11]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=3)=[N:12][C:8]=2[CH:7]=1)(=[O:5])=[O:4].[ClH:32].C(=O)([O-])[O-].[NH4+:37].[NH4+]>C(O)C>[ClH:32].[CH3:1][N:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[S:3]([C:6]1[CH:25]=[CH:24][C:9]2[N:10]([CH3:23])[C:11]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([C:21](=[NH:37])[NH2:22])=[CH:19][CH:20]=3)=[N:12][C:8]=2[CH:7]=1)(=[O:4])=[O:5]
Reactant: [NH4+]
Reactant: CN(c1ccccc1)S(=O)(=O)c1ccc2c(c1)nc(COc1ccc(C#N)cc1)n2C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Product: CN(c1ccccc1)S(=O)(=O)c1ccc2c(c1)nc(COc1ccc(C(=N)N)cc1)n2C
Yield: 46 %

Procedure:
Prepared analogously to Example 32 from 1-methyl-2-[(4-cyanophenyl)-oxymethyl]-benzimidazol-5-yl-sulphonic acid-N-methyl-N-phenyl-amide and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 46% of theory, C23H23N5O3S (449.5) ##EQU14##
Reaction SMILES: [CH2:1]([C:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=O)[CH2:2][CH2:3][CH2:4][CH3:5].C([NH2:20])C1C=CC=CC=1>[Pd]>[CH3:5][CH2:4][CH2:3][CH2:2][CH2:1][CH:6]([NH2:20])[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: NCc1ccccc1
Reactant: CCCCCC(=O)CCCCC
Agent: [Pd]
Product: CCCCCC(N)CCCCC
Reaction time: 5 h
Yield: 75.4 %

Procedure:
Diamylketone (12 g) was hydrogenated at 50 psi in the presence of 10% Pd/C (1.5 g) and benzylamine (8.31 g) at room temperature for 6 hours. Further catalyst (1.5 g) was added and the mixture was hydrogenated at 40° for 5 hours. The reaction mixture was filtered and evaporated to dryness (combined with the product from a previous 12 g hydrogenation). The oil was purified by column chromatography to give 6-undecylamine as an oil (9.1 g, 38%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([OH:14])=O)[C:6]3[CH2:15][CH2:16][N:17]([CH3:19])[CH2:18][C:5]=3[C:4]=2[CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][NH:28]1>ClCCl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH:27]3[CH3:26])=[O:14])[C:6]3[CH2:15][CH2:16][N:17]([CH3:19])[CH2:18][C:5]=3[C:4]=2[CH:3]=1
Reactant: CN1CCc2c(c3cc(Cl)ccc3n2CC(=O)O)C1
Reactant: CC1CCCCN1
Agent: CN(C)c1ccncc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: CC1CCCCN1C(=O)Cn1c2c(c3cc(Cl)ccc31)CN(C)CC2
Reaction time: 3 h
Yield: 19.4 %

Procedure:
A mixture of 2-(8-chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)acetic acid (125 mg, 0.45 mmol) and oxalyl chloride (2 ml) in dichloromethane (6.0 ml) was stirred at 25 deg C. for 3 h. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated to dryness. To the resulting crude dichloromethane (6.0 ml) and DMAP (64 mg, 0.52 mmol) was added followed by addition of 2-methylpiperidine (43 mg, 0.43 mmol). The resulting mixture was stirred at 25 deg C. for 14 h. After completion of the reaction (monitored by LCMS), solvent was removed in vacuo and purified by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL) to obtain 30 mg of 2-(8-chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(2-methylpiperidin-1-yl)ethanone as trifluoroacetic acid salt.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.[C-]#N.[Na+].[N:30]12CCN(CC1)C[CH2:31]2.O>CS(C)=O>[CH3:24][C:23]([CH3:26])([CH3:25])[CH2:22][N:8]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]2[CH:21]=[N:20][CH:19]=[N:18]2)=[CH:12][CH:11]=1)[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:31]#[N:30])[N:7]=1
Reactant: C1CN2CCN1CC2
Reactant: CC(C)(C)CN(Cc1ccc(Cn2cncn2)cc1)c1ccnc(Cl)n1
Agent: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)(C)CN(Cc1ccc(Cn2cncn2)cc1)c1ccnc(C#N)n1
Temperature: 70 °C
Reaction time: 5 h
Yield: 69167.1 %

Procedure:
(2-Chloro-pyrimidin-4-yl)-(2,2-dimethyl-propyl)-(4-[1,2,4]triazol-1-ylmethyl-benzyl)-amine (160 mg, 0.43 mmoles) and sodium cyanide (0.1 g, 2.2 mmoles) are dissolved in 5 ml of DMSO and 1,4-diaza bicyclo[2,2,2]octane (23 mg, 0.2 mmoles) is added at rt. The mixture is stirred at rt for 5 h at 70° C. Water is added and the organic layer is extracted with AcOEt, washed with brine, dried over magnesium sulfate and concentrated. The crude product is purified by silica gel column chromatography to give 50 g of desired 4-[(2,2-dimethyl-propyl)-(4-[1,2,4]triazol-1-ylmethyl-benzyl)-amino]-pyrimidine-2-carbonitrile in 32% yield.