Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)CCN(C)C.C([Li])(CC)C.[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[C:18]([OH:20])=[O:19].[Cl:25]C(Cl)(Cl)C(Cl)(Cl)Cl>O.O1CCCC1>[Cl:25][C:16]1[C:15]([F:14])=[C:23]([F:24])[CH:22]=[CH:21][C:17]=1[C:18]([OH:20])=[O:19]
Reactant: O=C(O)c1ccc(F)c(F)c1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Agent: CN(C)CCN(C)C
Agent: [Li]C(C)CC
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1ccc(F)c(F)c1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.6 %

Procedure:
To a mixture of N,N,N′,N′-tetramethylethylenediamine (8.40 mL) and tetrahydrofuran (75 mL) was added sec-butyllithium (1.0 mol/L cyclohexane solution, 55.7 mL) under an argon atmosphere at −78° C., and the mixture was stirred for 30 min. A mixture of 3,4-difluorobenzoic acid (4.00 g) and tetrahydrofuran (25 mL) was added dropwise to the reaction mixture at the same temperature over 30 min. After the reaction mixture was stirred for 30 min, a mixture of hexachloroethane (24.0 g) and tetrahydrofuran (40 mL) was added dropwise to the reaction mixture at the same temperature over 30 min. After stirring for 30 min while raising the temperature to room temperature, the reaction mixture was poured into water. The aqueous layer was washed with diisopropyl ether, acidified with 6 mol/L hydrochloric acid and extracted with diethyl ether. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was washed with diethyl ether to give the title product as a solid (yield: 2.95 g).
Reaction SMILES: C(O[C:6](=O)[N:7]([CH:9]([CH3:39])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:20]([CH3:26])=[N:21][CH:22]=[N:23][C:24]=2[CH3:25])=[C:15]([C:27]#[C:28][C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=2)[N:14]=1)=[O:11])C)(C)(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[CH3:25][C:24]1[C:19]([C:16]2[CH:17]=[CH:18][C:13]([NH:12][C:10](=[O:11])[CH:9]([NH:7][CH3:6])[CH3:39])=[N:14][C:15]=2[C:27]#[C:28][C:29]2[CH:38]=[CH:37][C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=2)=[C:20]([CH3:26])[N:21]=[CH:22][N:23]=1
Reactant: Cc1ncnc(C)c1-c1ccc(NC(=O)C(C)N(C)C(=O)OC(C)(C)C)nc1C#Cc1ccc2ccccc2c1
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CNC(C)C(=O)Nc1ccc(-c2c(C)ncnc2C)c(C#Cc2ccc3ccccc3c2)n1

Procedure:
A mixture of tert-butyl-N-[1-[[5-(4,6-dimethylpyrimidin-5-yl)-6-(2-naphthalen-2-yl-ethynyl)pyridin-2-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate E2g (12 mg, 0.02 mmol) and DCM:TFA (9:1, 5 ml) is stirred at RT for 60 minutes. The mixture is diluted with toluene (10 ml) and concentrated in vacuo. The product is purified by RP HPLC. Yield: 6 mg (61%). HPLC-MS: M+H=436; tR=1.38 min (*Method—1).
Reaction SMILES: N1C=CC=C[CH:2]=1.C([N:10]1[C:14]([NH2:15])=[N:13][C:12]([S:16]([NH:19][C:20]2[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:27])(=[O:18])=[O:17])=[N:11]1)(=O)C.[H-].[Na+].CI>CN(C)C=O>[NH2:15][C:14]1[NH:10][N:11]=[C:12]([S:16]([N:19]([C:20]2[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:27])[CH3:2])(=[O:18])=[O:17])[N:13]=1
Reactant: c1ccncc1
Reactant: CC(=O)n1nc(S(=O)(=O)Nc2c(Cl)cccc2Cl)nc1N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CI
Product: CN(c1c(Cl)cccc1Cl)S(=O)(=O)c1n[nH]c(N)n1
Reaction time: 0.5 h

Procedure:
9.80 g (22.8 mmol) of the pyridine salt of 1-acetyl-5-amino-N-(2,6-dichlorophenyl)-1,2,4-triazole-3-sulphonamide was dissolved in 300 ml dimethylformamide and 0.89 g (29.7 mmol) 80% sodium hydride added portionwise at room temperature. The mixture was stirred for a further 30 minutes and 1.7 ml (27.8 mmol) methyl iodide added. The mixture was allowed to stand overnight and concentrated. The residue was taken up in 2N aqueous sodium hydroxide and made slightly acidic by addition of 3N hydrochloric acid. The crystals were separated, washed with water and ether and recrystallised from acetonitrile.
Reaction SMILES: Cl[C:2](=[CH2:5])[C:3]#[N:4].Cl.[Cl:7][CH2:8]C(N)=N.[CH2:12]([N:14](CC)CC)[CH3:13]>CCO>[NH2:4][C:3]1[CH:13]=[CH:12][N:14]=[C:5]([CH2:8][Cl:7])[CH:2]=1
Reactant: N=C(N)CCl
Reactant: C=C(Cl)C#N
Reactant: CCN(CC)CC
Agent: Cl
Solvent: CCO
Product: Nc1ccnc(CCl)c1
Reaction time: 1 h

Procedure:
2-Chloroacrylonitrile (35 ml.) was added in portions over 15 minutes to a solution of chloroacetamidine hydrochloride (55 g.) and triethylamine (120 ml.) in EtOH (250 ml.) cooled to 10°. The temperature was allowed to rise to 40° over 1 hour. The mixture was cooled and filtered and the resulting solution evaporated in vacuo. The residue was taken up in EtOAc (600 ml.) from which a tar precipitated. The solution was treated with decolourising carbon, filtered and evaporated to give 4-amino-2-chloromethylpyridine as a brown solid.
Reaction SMILES: [NH2:1][CH:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][C:13]#[N:14])=[CH:9][CH:10]=2)[O:5][CH2:4][CH2:3]1.[C:15]1([CH:21]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=2)(=[O:29])=[O:28])[CH2:22][C:23](O)=[O:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(Cl)CCl.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:13]([CH2:12][C:8]1[CH:7]=[C:6]2[C:11]([CH:2]([NH:1][C:23](=[O:24])[CH2:22][CH:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:26][S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:37])[F:38])[CH:31]=3)(=[O:29])=[O:28])[CH2:3][CH2:4][O:5]2)=[CH:10][CH:9]=1)#[N:14]
Reactant: N#CCc1ccc2c(c1)OCCC2N
Reactant: O=C(O)CC(NS(=O)(=O)c1cccc(C(F)(F)F)c1)c1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: N#CCc1ccc2c(c1)OCCC2NC(=O)CC(NS(=O)(=O)c1cccc(C(F)(F)F)c1)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (4-amino-chroman-7-yl)-acetonitrile (Step A, 400 mg, 2.15 mmol) in CH2Cl2 (15 mL) was added 3-phenyl-3-(3-trifluoromethyl-benzenesulfonylamino)-propionic acid (802 mg, 2.15 mmol), HATU (408 mg, 1.07 mmol), EDC (453 mg, 2.36 mmol), and DIEA (0.7 mL, 4.29 mmol). The resulting mixture was stirred at RT for 18 h. Solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel. Elution with CH2Cl2:MeOH mixture (95:5) gave final compound. MS m/z: 544.12 (M+H). Calc'd. for C27H24F3N3O4S-543.56.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:12]([CH3:13])=[CH:11][C:10]([N:14]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:15]2[C:24]3[C:19](=[CH:20][C:21]([CH2:25][OH:26])=[CH:22][CH:23]=3)[C:18](=[O:27])[N:17]([CH:28]([CH3:30])[CH3:29])[N:16]=2)=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I(C1C=CC=CC=1C(O)=O)(=O)=[O:39].S(=O)(=O)(O)N.Cl([O-])=O.[Na+]>CS(C)=O.C(Cl)Cl.O>[C:34]([O:33][C:31]([N:14]([C:10]1[CH:11]=[C:12]([CH3:13])[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[N:9]=1)[C:15]1[C:24]2[C:19](=[CH:20][C:21]([C:25]([OH:39])=[O:26])=[CH:22][CH:23]=2)[C:18](=[O:27])[N:17]([CH:28]([CH3:29])[CH3:30])[N:16]=1)=[O:32])([CH3:35])([CH3:37])[CH3:36]
Reactant: Cc1cc(N(C(=O)OC(C)(C)C)c2nn(C(C)C)c(=O)c3cc(CO)ccc23)nn1C(=O)OC(C)(C)C
Reactant: O=C(O)c1ccccc1I(=O)=O
Agent: NS(=O)(=O)O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Solvent: CS(C)=O
Solvent: ClCCl
Product: Cc1cc(N(C(=O)OC(C)(C)C)c2nn(C(C)C)c(=O)c3cc(C(=O)O)ccc23)nn1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 24 h
Yield: 42.8 %

Procedure:
3-[tert-Butoxycarbonyl-(6-hydroxymethyl-3-isopropyl-4-oxo-3,4-dihydro-phthalazin-1-yl)-amino]-5-methyl-pyrazole-1-carboxylic acid tert-butyl ester (0.2 g, 0.39 mmol) was dissolved in DMSO (3 ml). To this was added 2-iodoxybenzoic acid (IBX) (0.22 g, 0.78 mmol) in one portion and the reaction mixture was stirred at RT for 24 hours. After this time, the reaction mixture was partitioned between EtOAc (20 ml) and water (20 ml), the organic layer was separated and washed with water (3×20 ml) before being dried (MgSO4), filtered and concentrated under vacuum. The resulting orange oil (0.197 g, 0.38 mmol) was dissolved in DCM (3 ml) and water (3 ml). To this was added sulfamic acid (0.037 g, 0.38 mmol) and the reaction mixture was stirred vigorously at 0° C. After 5 min, sodium chlorite (0.034 g, 0.38 mmol) was added in one portion and the mixture stirred for a further hour. After this time, the reaction mixture was diluted with DCM (20 ml) and washed with water (10 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated under vacuum. The resulting residue was purified by flash column chromatography (elution: 50% heptane, 50% EtOAc to 100% EtOAc) to give the title compound (0.088 g, 44% yield) as a white solid. MS (ESI+)=(M+H)+ 528.41.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:12]=[CH:11][C:10]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[NH2:31][OH:32].C(N(CC)CC)C>C(O)C>[Si:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:12]=[CH:11][C:10]=1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=[N:31][OH:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(C2CCCCC2=O)c(O[Si](C)(C)C(C)(C)C)c1
Reactant: NO
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)Oc1ccc(C2CCCCC2=NO)c(O[Si](C)(C)C(C)(C)C)c1
Temperature: 25 °C

Procedure:
To a round bottomed flask equipped with magnetic stirrer was added 4-{2,4-bis [tert-butyl(dimethyl)silyloxy]phenyl cyclohexanone (100 mg, 0.23 mmol) and ethanol (5 ml). To the stirred suspension was added hydroxylamine hydrochloride (32 mg, 0.46 mmol) and triethylamine (103 μl, 0.74 mmol), then the solution was heated under reflux temperature for 2.5 hr. The solution was allowed to cool to room temperature then evaporated to dryness in vacuo. The residue was partitioned between ethyl acetate (20 ml) and water (10 ml) and the layers separated. The aqueous layer was extracted with ethyl acetate (3×20 ml) and the combined organic layers washed with brine (10 ml), dried over magnesium sulfate, filtered and concentrated in vacuo. The title compound was isolated (103 mg, 100%) as a white. δH (CDCl3) 0.19 (6H, s), 0.24 (6H, s), 0.95 (9H, s), 1.02 (9H, s), 1.43-1.62 (2H, m), 1.77-1.87 (1H, m), 1.93-2.04 (2H, m), 2.18-2.24 (1H, m), 2.46-2.53 (1H, m), 3.05-3.15 (1H, m), 3.41-3.50 (1H, m), 6.30 (1H, d), 6.40 (1H, dd), 6.79 (1H, br), 6.92 (1H, d).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([N:13]2[C:17](=[O:18])[C:16]([CH3:20])([CH3:19])[N:15]([CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[C:14]2=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].CCN(C(C)C)C(C)C.[Cl:38][CH2:39][C:40](Cl)=[O:41]>ClCCCl>[CH3:19][C:16]1([CH3:20])[C:17](=[O:18])[N:13]([C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]([F:10])([F:11])[F:12])=[C:2]([NH:1][C:40](=[O:41])[CH2:39][Cl:38])[CH:3]=2)[C:14](=[O:28])[N:15]1[CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1
Reactant: CC1(C)C(=O)N(c2ccc(OC(F)(F)F)c(N)c2)C(=O)N1Cc1ccncc1
Reactant: O=C(Cl)CCl
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC1(C)C(=O)N(c2ccc(OC(F)(F)F)c(NC(=O)CCl)c2)C(=O)N1Cc1ccncc1
Temperature: -20 °C
Reaction time: 1 h

Procedure:
500 mg (1.27 mmol) 3-(3-amino-4-trifluormethoxy-phenyl)-5,5-dimethyl-1-pyridin-4-ylmethyl-imidazolidine-2,4-dione and 172 mg (1.33 mmol) Hünig's base were dissolved in 20 ml 1,2-dichloroethane. The mixture was cooled to −20° C. and treated with a solution of 143 mg (1.27 mmol) chloroacetylchlorid in 15 ml 1,2-dichloroethane. After stirring 1 h at 0° C., 5 ml ethanolic hydrochlric acid were added and the mixture evaporated to dryness. The raw material, containing huening's base hydrochloride was used without further purification.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[NH:16][C:15](=O)[CH2:14][O:13][C:12]([CH3:23])([C:18]4[CH:22]=[CH:21][S:20][CH:19]=4)[C:11]=3[CH:24]=2)=[CH:5][CH:4]=[C:3]1[C:25]#[N:26].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1>>[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[NH:16][C:15](=[S:36])[CH2:14][O:13][C:12]([CH3:23])([C:18]4[CH:22]=[CH:21][S:20][CH:19]=4)[C:11]=3[CH:24]=2)=[CH:5][CH:4]=[C:3]1[C:25]#[N:26]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: Cn1c(C#N)ccc1-c1ccc2c(c1)C(C)(c1ccsc1)OCC(=O)N2
Product: Cn1c(C#N)ccc1-c1ccc2c(c1)C(C)(c1ccsc1)OCC(=S)N2

Procedure:
Prepared from 1-methyl-5-[5-methyl-2-oxo-5-(3-thienyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-7-yl]-1H-pyrrole-2-carbonitrile and Lawesson's reagent generally according to example 10. 1H NMR (DMSO-d6): δ 12.11 (s, 1H), 7.45-7.54 (m, 3H), 7.37 (d, J=1.62 Hz, 1H), 7.29 (dd, J=2.87, 1.3 Hz, 1H), 7.06 (dd, J=5.02, 1.28 Hz, 1H), 7.03 (d, J=4.09 Hz, 1H), 6.37 (d, J=4.09 Hz, 1H), 4.46 (d, J=15.33 Hz, 1H), 4.35 (d, J=15.33 Hz, 1H), 3.70 (s, 3H), 1.99 (s, 3H); MS (ESI) m/z 378 ([M−H]−); Anal. calcd for C20H17N3OS2: C, 63.3; H, 4.52; N, 11.07. Found: C, 63.06; H, 4.76; N, 10.29.
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16](/[CH:26]=[CH:27]/[C:28]2[N:44]=[C:31]3[CH:32]([C:36]4[CH:41]=[CH:40][C:39]([S:42][CH3:43])=[CH:38][CH:37]=4)[CH2:33][CH2:34][CH2:35][N:30]3[N:29]=2)[CH:17]=[CH:18][C:19]=1[N:20]1[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]1.C(OCC)(=O)C.[Cl-].[Na+].[OH2:53]>C(Cl)(Cl)Cl>[CH3:43][S:42]([C:39]1[CH:38]=[CH:37][C:36]([CH:32]2[CH2:33][CH2:34][CH2:35][N:30]3[N:29]=[C:28](/[CH:27]=[CH:26]/[C:16]4[CH:17]=[CH:18][C:19]([N:20]5[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]5)=[C:14]([O:13][CH3:12])[CH:15]=4)[N:44]=[C:31]23)=[CH:41][CH:40]=1)(=[O:9])=[O:53]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1cc(/C=C/c2nc3n(n2)CCCC3c2ccc(SC)cc2)ccc1-n1cnc(C)c1
Reactant: O
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: COc1cc(/C=C/c2nc3n(n2)CCCC3c2ccc(S(C)(=O)=O)cc2)ccc1-n1cnc(C)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
mCPBA (6.83 mg) was added to a solution of (−)-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(4-methylsulfanylphenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine obtained in Example 7 (4.5 mg) in chloroform (1 mL), and the reaction solution was stirred at room temperature for one hour. Brine and ethyl acetate were added to the reaction solution and the organic layer was separated. The resulting organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: ethyl acetate→ethyl acetate:methanol=9:1) to obtain 0.44 mg of the title compound.
Reaction SMILES: C(=[C:8]1/[CH2:9][CH2:10][C:11]2[C:12]/1=[N:13][CH:14]=[C:15]([Br:17])[CH:16]=2)/C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[OH:38]>C(Cl)Cl>[Br:17][C:15]1[CH:16]=[C:11]2[CH2:10][CH2:9][C:8](=[O:38])[C:12]2=[N:13][CH:14]=1
Reactant: Brc1cnc2c(c1)CC/C2=C\c1ccccc1
Reactant: CO
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: O=C1CCc2cc(Br)cnc21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 96 %

Procedure:
A solution of (E)-7-benzylidene-3-bromo-6,7-dihydro-5H-cyclopenta[b]pyridine (1.61 g, 5.63 mmol) in MeOH (75 mL) and DCM (75 mL) was cooled to −78° C. and a stream of ozone in oxygen was bubbled through the solution for 10 min until the solution turned light blue. Oxygen was pass through the solution for 10 min until the solution turned colorless. Triphenylphosphine (3.63 g, 13.8 mmol) was added and the reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 1.5 h and then concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (80 g, 30% to 70% EtOAc in heptane) to give 3-bromo-5H-cyclopenta[b]pyridin-7(6H)-one (1.14 g, 5.38 mmol, 96% yield) as a yellow solid. MS m/z=211.9 [M+H]+. Calculated for C8H6BrNO 211.0.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[C:9]([S:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]3[C:26](=[O:27])[C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[C:18]4[S:19](=[O:24])(=[O:23])[CH2:20][CH2:21][CH2:22][N:17]4[C:16]3=[O:34])=[CH:8][CH:7]=[CH:6][C:5]=12.[I-].C[CH:37]=[N+:38]=[CH:39]C.[C:41](#N)C>>[CH3:37][N:38]([CH2:39][C:3]1[N:4]2[C:9]([S:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]3[C:26](=[O:27])[C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[C:18]4[S:19](=[O:24])(=[O:23])[CH2:20][CH2:21][CH2:22][N:17]4[C:16]3=[O:34])=[CH:8][CH:7]=[CH:6][C:5]2=[N:1][CH:2]=1)[CH3:41]
Reactant: O=c1c(-c2ccccc2)c2n(c(=O)n1CCCCSc1cccc3nccn13)CCCS2(=O)=O
Reactant: CC=[N+]=CC
Reactant: CC#N
Agent: [I-]
Product: CN(C)Cc1cnc2cccc(SCCCCn3c(=O)c(-c4ccccc4)c4n(c3=O)CCCS4(=O)=O)n12

Procedure:
To a solution of 0.45 g (0.93 mmol) of 7-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]-1,1-dioxo-9-phenyl-3,4-dihydro-2H,6H-pyrimido[6,1-b][1,3]thiazine-6,8(7H)-dione in 10 ml of acetonitrile, 0.258 g (1.4 mmol) of N,N-dimethylmethylene ammonium iodide (Eschenmoser's salt) was added at room temperature, followed by refluxing for 2 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with saturated aqueous sodium hydrogen carbonate and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, chloroform/methanol=25/1) to yield 0.40 g (77.6%, light yellow oily substance) of the desired product.
Reaction SMILES: [CH2:1]([C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]=1[OH:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(O)(=O)C.[N+:28]([O-])([OH:30])=[O:29]>O>[CH2:1]([C:13]1[CH:22]=[C:21]([N+:28]([O-:30])=[O:29])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]=1[OH:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=[N+]([O-])O
Reactant: CCCCCCCCCCCCc1ccc2ccccc2c1O
Solvent: O
Solvent: CC(=O)O
Product: CCCCCCCCCCCCc1cc([N+](=O)[O-])c2ccccc2c1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 50 parts of 2-n-dodecyl-1-naphthol in 500 parts of glacial acetic acid was added 28 parts of nitric acid (specific gravity 1.4). The solution was stirred at ambient temperature for 1 hour and then poured into 2000 parts of water. The resulting mixture was extracted with 1400 parts of ether. The ether layer was separated; washed once with water (2000 parts), twice with 10% aqueous sodium bicarbonate solution (2000 parts), and finally with water (2000 parts). The ether solution was dried with anhydrous magnesium sulfate and evaporated to afford 56 parts of 2-n-dodecyl-4-nitro-1-naphthol as a viscous yellow oil, nD25 = 1.5454, which slowly crystallized to a waxy yellow solid on standing.
Reaction SMILES: Cl.C1(N2CCN([CH2:14][CH2:15][CH2:16][CH2:17][N:18]3[C:27](=[O:28])[C:26]4[CH:29]=[CH:30][CH:31]=[C:24]5[C:25]=4[C:20](=[CH:21][CH:22]=[CH:23]5)[C:19]3=[O:32])CC2)C=CC=CC=1.[Br:33][CH2:34]CCCCBr.BrCCCCBr>>[Br:33][CH2:34][CH2:14][CH2:15][CH2:16][CH2:17][N:18]1[C:27](=[O:28])[C:26]2[CH:29]=[CH:30][CH:31]=[C:24]3[C:25]=2[C:20](=[CH:21][CH:22]=[CH:23]3)[C:19]1=[O:32]
Reactant: O=C1c2cccc3cccc(c23)C(=O)N1CCCCN1CCN(c2ccccc2)CC1
Reactant: BrCCCCCBr
Agent: Cl
Solvent: BrCCCCBr
Product: O=C1c2cccc3cccc(c23)C(=O)N1CCCCCBr

Procedure:
Following the procedure of part (a) of example 34 but substituting 1,5-dibromopentane for the 1,4-dibromobutane, one obtains 2-(5-bromopentyl)-1H-benz[de]isoquinoline-1,3(2H)-dione; m.p. 113°-115°.
Reaction SMILES: O[N:2]1[C:6]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[C:5]([CH2:13][CH3:14])[N:4]=[C:3]1[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=1.P(Cl)(Cl)Cl.O.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:24][O:23][C:17]1[CH:16]=[C:15]([C:3]2[NH:2][C:6]([C:7]3[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=3)=[C:5]([CH2:13][CH3:14])[N:4]=2)[CH:20]=[CH:19][C:18]=1[O:21][CH3:22]
Reactant: CCc1nc(-c2ccc(OC)c(OC)c2)n(O)c1-c1cccnc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClP(Cl)Cl
Solvent: O
Solvent: CN(C)C=O
Product: CCc1nc(-c2ccc(OC)c(OC)c2)[nH]c1-c1cccnc1
Reaction time: 2 h
Yield: 50.3 %

Procedure:
To a solution of 1-hydroxy-2-(3,4-dimethoxyphenyl)-4-ethyl-5-(3-pyridyl)imidazole (1.86 g) in N,N-dimethylformamide (38 ml) was added phosphorus trichloride (0.10 ml) under ice-cooling. The mixture was stirred for 2 hours at 5° to 10° C. The reaction mixture was poured into water, neutralized with aqueous sodium bicarbonate, and extracted with ethyl acetate. The extract was washed with water, dried, and evaporated. The residue was subjected to column chromatography on silica gel eluting with a mixture of chloroform and methanol (methanol 1% to 5%). The fractions were collected and evaporated to give 2-(3,4-dimethoxyphenyl)-4-ethyl-5-(3-pyridyl)imidazole (0.89 g), which was diluted with methanol (8 ml). 1.2 Equivalent of hydrogen chloride gas was bubbled thereinto and diethyl ether was added to the mixture under cooling. The precipitate was collected and dried to give 2-(3,4-dimethoxyphenyl)-4-ethyl-5-(3-pyridyl)imidazole hydrochloride (0.43 g).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[N:12]=[C:11]([C:20]([NH:22][CH2:23][CH2:24][O:25][CH3:26])=[O:21])[N:10]=1.[N:27]#[C:28]Br.O>O1CCCC1.C(N(CC)CC)C>[C:28]([NH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[N:12]=[C:11]([C:20]([NH:22][CH2:23][CH2:24][O:25][CH3:26])=[O:21])[N:10]=1)#[N:27]
Reactant: N#CBr
Reactant: COCCNC(=O)c1nc(N[C@H]2CCCC[C@H]2N)c2cc(C)ccc2n1
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COCCNC(=O)c1nc(N[C@H]2CCCC[C@H]2NC#N)c2cc(C)ccc2n1
Reaction time: 0.5 h
Yield: 55.5 %

Procedure:
In an argon atmosphere, to a solution of 3.30 g of 4-{[(1S,2R)-2-aminocyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamide in 80 ml of tetrahydrofuran, 1.54 ml of triethylamine and 978 mg of cyanogen bromide were sequentially added at −20° C., and the mixture was stirred at the same temperature for 0.5 hour. Water was added to the reaction solution, and the mixture was subjected to an extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (chloroform:methanol=50:1), whereby 1.96 g of a desired compound was obtained as a pale yellow crystal.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=[CH:7][C:5]=2[CH:6]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:38]([O:40][C:41]([C:43]1([NH2:52])[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44]1)=[O:42])[CH3:39].CCN(C(C)C)C(C)C>CCO.ClCCl.C(Cl)Cl>[CH2:38]([O:40][C:41]([C:43]1([NH:52][C:11]([C:10]2[C:4]3[O:3][C:2]([CH3:1])=[CH:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)=[O:13])[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44]1)=[O:42])[CH3:39]
Reactant: Cc1cc2cccc(C(=O)O)c2o1
Reactant: CCOC(=O)C1(N)Cc2ccccc2C1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: CCOC(=O)C1(NC(=O)c2cccc3cc(C)oc23)Cc2ccccc2C1
Yield: 136.9 %

Procedure:
To a 25 mL vial containing a stirring bar, 2-methylbenzofuran-7-carboxylic acid (0.343 g, 1.95 mmol) is charged with dry DCM (6 mL). Stirring is initiated. HBTU (738 mg, 1.95 mmol) is added. The 2-aminoindane-2-carboxylic acid ethyl ester (400 mg, 1.95 mmol) is added followed by DIPEA (0.75 mL, 4.31 mmol). The reaction is allowed to stir for 16 h. Analysis by tlc of the reaction mixture (silica, 10% EtOH/dichloromethane) indicates complete consumption of the starting amine. The contents of the reaction flask are diluted with EtOAc (50 mL) and transferred to a separatory funnel. This is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 0.97 g of yellow oil. This material is dissolved in 10 mL of DCM. This is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 15% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 90% over 15 column volumes and then 100% EtOAc for 2 column volumes with a ramp of 1 column volume. 25 mL fractions are collected. Fractions 2 through 7 are combined and evaporated in vacuo to a constant weight to give 0.63 g of amorphous white solid.