Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([C:16]#[N:17])=[C:4](Cl)[N:3]=1.CC(C)([O-])C.[K+].[OH:25][CH2:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1>CS(C)=O.C(O)(=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([C:16]#[N:17])=[C:4]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=2)[N:3]=1
Reactant: N#Cc1c(N)nc(Cl)c(C#N)c1-c1ccccc1
Reactant: OCc1ccncc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CS(C)=O
Product: N#Cc1c(N)nc(OCc2ccncc2)c(C#N)c1-c1ccccc1
Temperature: 60 °C
Reaction time: 16 h

Procedure:
102 mg (0.4 mmol) of 2-amino-6-chloro-4-phenyl-3,5-pyridinedicarbonitrile [Quintela et al., Heterocycles 38, 1299-1305 (1994)] are, together with 54 mg (0.48 mmol) of potassium tert-butoxide and 131 mg (1.2 mmol) of 4-hydroxymethylpyridine, dissolved in 1.5 ml of DMSO, and the mixture is stirred at 60° C. for about 16 h. The reaction mixture is acidified with two drops of glacial acetic acid. The solution is purified by preparative HPLC on reversed-phase silica gel (gradient: water+0.1% formic acid/acetonitrile 90:1010:90 in 12 minutes).
Reaction SMILES: N[C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[NH2:8].[C:15]([O:19][C:20]([NH:22][C:23]1([C:28](O)=[O:29])[CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:15]([O:19][C:20]([NH:22][C:23]1([C:28]([NH:8][C:7]2[CH:6]=[CH:5][C:4](/[CH:9]=[CH:10]/[C:11]([O:13][CH3:14])=[O:12])=[CH:3][CH:2]=2)=[O:29])[CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]
Reactant: COC(=O)/C=C/c1ccc(N)c(N)c1
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CCCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)/C=C/c1ccc(NC(=O)C2(NC(=O)OC(C)(C)C)CCCC2)cc1
Reaction time: 8 h

Procedure:
To a solution of methyl (2E)-3-(3,4-diaminophenyl)acrylate (from Step 3.1 eq), 1-[(tert-butoxycarbonyl)amino]cyclopentanecarboxylic acid (1 eq) in DMF (0.02 M), HATU (1 eq) and DIPEA (3 eq) were added. The reaction mixture was left at RT with stirring overnight. The resulting mixture was partitioned between EtOAc and HCl (1 N). The combined EtOAc layers were washed with brine, and the organic phase was dried over Na2SO4, separated, and evaporated in vacuo to afford methyl (2E)-3-{4-[({1-[(tert-butoxycarbonyl)amino]cyclopentyl}carbonyl)amino]phenyl}acrylate, which was used without further purification. MS (ES+) m/z 404 (M+H)+. The foregoing product was dehydrated by heating it at 65° C. in presence of acetic acid. (0.16 M); the reaction residue was purified by RP-HPLC (Conditions Symmetry (Waters) C18 Column, 7 micron, 19×300 mm; flow: 20 mL/min; Gradient: A H2O+0.1% TFA; B: MeCN+0.1% TFA; 70% A isocratic for 2 min., linear to 20% A in 16 min isocratic for 0.5 min. and linear to 10% A for 2 min). Fractions containing pure product were pooled and lyophilized to give methyl (2E)-3-(2-{1-[(tert-butoxycarbonyl)amino]-cyclopentyl}-1H-benzimidazol-5-yl)acrylate. MS (ES−) m/z 384 (M−H)−.
Reaction SMILES: [F:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([CH2:11][C@H:12]([CH3:15])[CH2:13]I)[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.[CH2:18]([CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21]>CC#N>[CH2:18]([CH:22]1[CH2:27][CH2:26][N:25]([CH2:13][C@@H:12]([CH3:15])[CH2:11][N:6]2[C:5]3[CH:16]=[CH:17][C:2]([F:1])=[CH:3][C:4]=3[O:9][CH2:8][C:7]2=[O:10])[CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21]
Reactant: CCCCC1CCNCC1
Reactant: C[C@H](CI)CN1C(=O)COc2cc(F)ccc21
Solvent: CC#N
Product: CCCCC1CCN(C[C@@H](C)CN2C(=O)COc3cc(F)ccc32)CC1
Yield: 63.7 %

Procedure:
A microwave vial was charged with (S)-7-fluoro-4-(3-Iodo-2-methylpropyl)-4H-benzo[1,4]oxazin-3-one (111MF20) (0.274 g, 0.78 mmol) and 4-butylpiperidine (0.226 g, 1.60 mmol) in MeCN (4 mL) and sealed. After microwave irradiation, 100° C., 60 min, the reaction mixture was purified by cation exchange CC followed by flash CC (SiO2; CH2Cl2/MeOH 50:1) to give the title compound (112KK04) (0.180 g, 63%). 1H NMR (CD3OD) δ 7.24-7.21 (m, 1H), 6.81-6.76 (m, 2H), 4.60 (ABq, J=17.4 Hz, J=15.1 Hz, CH2), 3.98 (dd, J=14.3 Hz, J=5.9 Hz, 1H), 3.87 (dd, J=14.3 Hz, J=7.6 Hz, 1H), 2.86 (d, J=11.0 Hz, 1H), 2.73 (d, J=9.8 Hz, 1H), 2.28-2.23 (m, 1H), 2.16-2.08 (m, 2H), 1.93-1.81 (m, 2H), 1.79-1.62 (m 2H), 1.32-1.13 (m, 9H), 0.93-0.88 (m, 2 CH3); 13C NMR (CD3OD) δ 166.1, 160.3 (d, J=242.3 Hz), 148.1 (d, J=11.9 Hz), 126.4 (d, J=2.9 Hz), 117.8 (d, J=9.4 Hz), 109.9 (d, J=22.9 Hz), 105.7 (d, J=26.1 Hz), 68.6, 65.1, 56.3, 55.4, 46.6, 37.5, 37.0, 33.6, 33.4, 30.1, 29.9, 24.0, 17.2, 14.4.
Reaction SMILES: [CH:1]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:2]=1[C:3](=[O:18])[N:4]1[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:5]1=[N:6]2.[Na].[H-].[Na+].[CH3:22][C:23]1[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>CN(C)C=O>[CH3:22][C:23]1[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:24]=1[C:25]([N:11]1[C:5]2=[N:6][C:7]3[C:2]([C:3](=[O:18])[N:4]2[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]1=2)=[CH:1][CH:10]=[CH:9][CH:8]=3)=[O:26]
Reactant: O=c1c2ccccc2nc2[nH]c3ccccc3n12
Reactant: Cc1ccc(C(=O)Cl)c(C)c1
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: CN(C)C=O
Product: Cc1ccc(C(=O)n2c3ccccc3n3c(=O)c4ccccc4nc23)c(C)c1
Temperature: 0 °C

Procedure:
Benzimidazo[2,1-b]quinazolin-12(6H)one, 7.05 g. in 200 ml. of dry dimethylformamide was converted to the sodium derivative with sodium hydride according to the procedures described in previous examples and 2,4-dimethylbenzoyl chloride, 5.8 g. in 25 ml. of dimethylformamide were added dropwise with vigorous stirring. The reaction mixture was stirred for an additional hour and then poured into ice water. The precipitate which formed was filtered, washed with water, dried and twice recrystallized from benzene to yield 6-(2,4-dimethylbenzoyl)benzimidazo[2,1-b]quinazolin-12(6H)one as a crystalline solid melting at about 213°-214° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[NH:13][N:12]=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:16][Si:17]([CH3:24])([CH3:23])[CH2:18][CH2:19][O:20][CH2:21]Cl>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[N:13]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:24])([CH3:23])[CH3:16])[N:12]=[N:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: Brc1ccc(Sc2cnn[nH]2)cc1
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C[Si](C)(C)CCOCn1nncc1Sc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A mixture of compound 63a (360 mg, 1.40 mmol) and 60% NaH (135 mg, 3.40 mmol) in DMF (2 mL) was stirred for 20 min at rt. At that time, 2-(trimethylsilyl) ethoxymethyl chloride (0.558 mL, 3.10 mmol) was added and the resulting mixture was stirred at rt for 12 h. The reaction mixture was diluted with DCM (300 mL) and washed with saturated NH4Cl solution (200 mL), water (200 mL) and brine (200 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0-50% EtOAc/heptanes) to give compound 63b. Mass Spectrum LCMS, ESI (pos.) Calcd. for C14H20BrN3OSSi: 386.1 [M+H]. found 386.2.
Reaction SMILES: Br[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][NH:10][C:4]=2[CH:3]=1.[CH3:13][N:14]([CH2:19][C:20]1[O:21][C:22]2[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=2[C:24]=1[CH3:25])[C:15](=[O:18])[CH:16]=[CH2:17].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[CH3:13][N:14]([CH2:19][C:20]1[O:21][C:22]2[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=2[C:24]=1[CH3:25])[C:15](=[O:18])/[CH:16]=[CH:17]/[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][NH:10][C:4]=2[CH:3]=1
Reactant: Brc1cnc2c(c1)NCCCN2
Reactant: C=CC(=O)N(C)Cc1oc2ccccc2c1C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1c(CN(C)C(=O)/C=C/c2cnc3c(c2)NCCCN3)oc2ccccc12
Temperature: 100 °C
Reaction time: 0.25 h
Yield: 44.7 %

Procedure:
A solution of 8-bromo-2,3,4,5-tetrahydro-1H-pyrido[2,3-b][1,4]diazepin (0.15 g, 0.66 mmol), N-methyl-N-((3-methyl benzofuran-2-yl)methyl)acrylamide (0.30 g, 1.32 mmol), (i-Pr)2EtN (0.34 mL, 2.0 mmol) tn DMF (7 mL) was de-oxygenated with Ar for 30 min. Pd(OAc)2 (15 mg, 0.066 mmol) and P(o-tol)3 (40 mg, 0.13 mmol) was added and the solution was de-oxygenated for an additional 15 min. The reaction was heated to 100° C. for 18 hrs at which time the reaction was cooled to room temperature and then filtered through a short-column of silica washing with EtOAc (20 mL). The filtrate was washed with brine (2×30 mL), dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 99:1) gave the title compound (111 mg, 45%) as a yellow powder; 1H NMR (400 MHz, DMSO-d6) δ7.75 (s, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.48 (d, J=7.6, 1H), 7.43 and 7.39 (2×s, 1H), 7.35-7.22 (m, 3H), 7.08 and 6.82 (2×d, J=15, 1H), 6.22 (s, 1H), 5.25 (s, 1H), 4.90 and 478 (2×s, 2H), 3.14-2.93 (m, 7H), 2.26 (s, 3H), 1.68 (m, 2H); ESI MS m/z 377 [C22H24N4O2+H]+
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]([CH2:13][O:14][CH3:15])([CH3:12])[CH2:10][CH2:9][CH2:8][S:7][C:6]=2[CH:16]=1.C[O:18][C:19](=[O:28])[C:20]1[CH:25]=[CH:24][C:23]([C:26]#[CH:27])=[CH:22][CH:21]=1>N1CCCCC1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][O:14][CH2:13][C:11]1([CH3:12])[CH2:10][CH2:9][CH2:8][S:7][C:6]2[CH:16]=[C:2]([C:27]#[C:26][C:23]3[CH:24]=[CH:25][C:20]([C:19]([OH:28])=[O:18])=[CH:21][CH:22]=3)[CH:3]=[CH:4][C:5]1=2
Reactant: C#Cc1ccc(C(=O)OC)cc1
Reactant: COCC1(C)CCCSc2cc(Br)ccc21
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCNCC1
Product: COCC1(C)CCCSc2cc(C#Cc3ccc(C(=O)O)cc3)ccc21
Temperature: 80 °C
Yield: 46.3 %

Procedure:
To 478 mg (1.59 mmol) of 8-bromo-5-methoxymethyl-5-methyl-2,3,4,5-tetrahydrobenzo[b]thiepine, dissolved in 2.9 ml of piperidine, was added successively 4.8 mg (0.02 eq.) of CuI, 7.0 mg (0.02 eq.) of Ph3P, and 24.1 mg (0.01 eq.) of (Ph3P)4Pd. After heating to 80° C., a solution of 508 mg (2 eq.) of 4-ethynyl-benzoic acid methyl ester in 2.8 ml of piperidine was added within 2 h via dropping funnel and then kept at this temperature for 3 additional h. After cooling, the reaction mixture was poured onto crushed ice/ HCl diluted, extracted with diethylether, the organic phase was washed with water, dried over magnesium sulfate, filtrated and evaporated to dryness. Flash chromatography (SiO2, hexane/ethylacetate 95/5) yielded 270 mg of the title compound as colorless oil.
Reaction SMILES: [CH3:1][C:2]1([CH2:16][C:17]#[CH:18])[CH2:10][C:9]2[C:4](=[C:5]([Cl:14])[C:6]([Cl:13])=[C:7]([O:11]C)[CH:8]=2)[C:3]1=[O:15].[ClH:19].N1C=CC=CC=1>O>[Cl:19][C:17](=[CH2:18])[CH2:16][C:2]1([CH3:1])[CH2:10][C:9]2[C:4](=[C:5]([Cl:14])[C:6]([Cl:13])=[C:7]([OH:11])[CH:8]=2)[C:3]1=[O:15]
Reactant: Cl
Reactant: C#CCC1(C)Cc2cc(OC)c(Cl)c(Cl)c2C1=O
Solvent: c1ccncc1
Solvent: O
Product: C=C(Cl)CC1(C)Cc2cc(O)c(Cl)c(Cl)c2C1=O
Temperature: 185 °C

Procedure:
A stirred mixture of 2-methyl-2-propargyl-5-methoxy-6,7-dichloro-1-indanone (11 g., 0.039 mole) and pyridine hydrochloride (110 g.) is heated at 185° C. for one hour, then poured into water (500 ml.). The product which separates is recrystallized from ethanol-water affording 6.5 g. of 2-(2-chloroallyl)-2-methyl-5-hydroxy-6,7-dichloro-1-indanone, m.p. 183° C.
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:16][CH2:17][CH2:18]Br>CN(C)C=O>[O:2]1[C:1]2[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=2[O:4][CH2:18][CH2:17][CH2:16]1
Reactant: Oc1ccccc1O
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: c1ccc2c(c1)OCCCO2
Yield: 41.3 %

Procedure:
110 g of pyrocatechol, 276 g of potassium carbonate and 303 g of 1,3-dibromopropane were stirred at 120° C. for 48 hours in 800 ml of absolute dimethylformamide. The cooled suspension was filtered under suction, the residue was back-washed with ether and the filtrate was poured into 4 l of water. This was extracted with ether. The ether extract was washed twice with 3 N sodium hydroxide and then neutral with water, dried over sodium sulfate and evaporated in vacuo. The residue (146.6 g) was distilled at 11 mm/118°-120° C. 61.9 g (41.2% of theory) of 3,4-dihydro-2H-1,5-benzodioxepine were obtained.
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].C(OC(C)C)(C)C.Cl[C:14]([C:16]([F:27])([F:26])[CH:17]([O:20][C:21](=[O:25])[C:22]([CH3:24])=[CH2:23])[CH2:18][CH3:19])=[O:15]>>[C:1]([NH:5][C:14]([C:16]([F:26])([F:27])[CH:17]([O:20][C:21](=[O:25])[C:22]([CH3:24])=[CH2:23])[CH2:18][CH3:19])=[O:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=C(C)C(=O)OC(CC)C(F)(F)C(=O)Cl
Reactant: CC(C)(C)N
Solvent: CC(C)OC(C)C
Product: C=C(C)C(=O)OC(CC)C(F)(F)C(=O)NC(C)(C)C
Yield: 112.7 %

Procedure:
In a 50-mL glass flask with a dropping funnel, 3.0 g (41.6 mmol/2.0 eq) of tertiary butylamine and 5.0 g of diisopropyl ether were added and stirred. Subsequently, 5.0 g (20.8 mmol) of methacrylic acid 1-chlorocarbonyl-1,1-difluoro-2-butyl ester was dropped into the glass flask. The resulting solution was stirred for 10 minutes at room temperature. The completion of the reaction was confirmed by 19F NMR. After that, the solution was separated into an organic layer and an aqueous layer with the addition of 10 mL of water and 5 mL of diisopropyl ether. The thus-obtained organic layer was concentrated under a reduced pressure. With this, 6.5 g of methacrylic acid 1-tert-butylaminocarbonyl-1,1-difluoro-2-butyl ester was obtained as a white crystalline substance (yield: 99%, purity: 88%).
Reaction SMILES: [CH:1]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[CH:2][CH2:3][CH3:4].C(=O)([O-])[OH:12].[Na+].ClC1C=CC=C(C(OO)=O)C=1>ClCCl.O>[CH2:2]([CH:3]1[CH2:4][O:12]1)[CH2:1][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C([O-])O
Reactant: CCC=Cc1ccccc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: c1ccc(CCC2CO2)cc1
Reaction time: 4 h

Procedure:
To a suspension of but-3-butenylbenzene (3 ml) and sodium hydrogen carbonate (2.5 g) in a mixture of dichloromethane (200 ml) and water (60 ml) was added small portions of m-chloroperbenzoic acid (3.5 g) at room temperature, and the mixture was stirred at the same temperature for 4 hours. After separation, the organic layer was successively washed with saturated aqueous sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=100:3) to give 2-phenethyloxirane (970 mg).
Reaction SMILES: [OH:1][N:2]=[C:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH:11]=[CH:12][N:13]=2)[CH:10]=1)[NH2:4].[C:14](Cl)(=O)[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1.Cl.N>>[N:13]1[CH:12]=[CH:11][N:9]2[CH:10]=[C:5]([C:3]3[N:4]=[C:14]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[O:1][N:2]=3)[CH:6]=[CH:7][C:8]=12
Reactant: O=C(Cl)c1cccnc1
Reactant: NC(=NO)c1ccc2nccn2c1
Agent: Cl
Agent: N
Product: c1cncc(-c2nc(-c3ccc4nccn4c3)no2)c1

Procedure:
The title compound was prepared according to Method D using N′-hydroxyimidazo[1,2-a]pyridine-6-carboximidamide (Bionet) and nicotinoyl chloride, hydrochloric Acid (Aldrich). 1H NMR (300 MHz, DMSO-d6) δ 7.62-7.91 (m, 4 H), 8.20 (s, 1 H), 8.56 (dt, J=8.1, 1.9 Hz, 1 H), 8.92 (dd, J=4.7, 1.7 Hz, 1 H) ppm; MS (DCI/NH3) m/z 264 (M+H)+.
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[O:9]=[C:10]([CH3:20])[CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]>CS(C)=O>[CH3:20][C:10]1([CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:2][O:9]1
Reactant: CC(=O)CCC(=O)OC(C)(C)C
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)CCC1(C)CO1
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 67.2 %

Procedure:
Trimethylsulfoxonium iodide (19.54 g, 88.78 mmol) was added to a suspension of sodium hydride (3.71 g, 92.82 mmol) in DMSO (50 ml) while cooling in an ice-bath, and the mixture was stirred for 2.5 hours. To which a solution of tert-butyl 4-oxopentanoate (13.90 g, 80.71 mmol) in DMSO (20 ml) was added, and the mixture was stirred at room temperature for 15 hours. The mixture was poured into ice water, extracted with diethyl ether. The extract was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to afford tert-butyl 3-(2-methyl-2-oxiranyl)propionate (10.1 g, yield 67%) as a pale yellow oil.
Reaction SMILES: [C:1]([Cl:4])(Cl)=[O:2].[O:5]([CH2:12][CH2:13][NH:14][CH2:15][CH2:16][CH3:17])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C(OCC)(=O)C>[O:5]([CH2:12][CH2:13][N:14]([CH2:15][CH2:16][CH3:17])[C:1]([Cl:4])=[O:2])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCCNCCOc1ccccc1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: CCCN(CCOc1ccccc1)C(=O)Cl

Procedure:
To 100 ml. of mechanically stirred, refluxing dry ethyl acetate was introduced a steady flow of phosgene gas followed by the dropwise addition of 22.4g. N-2-phenoxyethyl-N-propylamine in 100 ml. dry ethyl acetate over a period of 45 minutes. On completion of the addition, the reaction mixture was boiled under reflux with stirring, whilst continuing the flow of phosgene for a further three hours. The solvent was removed on the steam bath, the last traces being extracted under vacuum to give N-2-phenoxyethyl-N-propylcarbamoyl chloride.
Reaction SMILES: [H-].[Na+].CS(C)=O.[Br-].[C:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:10])=[O:9].[C:37]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)(=O)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O1CCCC1>[C:38]1([C:37]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:8]([OH:10])=[O:9])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: O=C(O)CCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: C1CCOC1
Product: O=C(O)CCCCCCC=C(c1ccccc1)c1ccccc1
Yield: 55.5 %

Procedure:
The reaction was carried out as in Example 87 using the following reagents: sodium hydride (56% dispersion in oil; 8.6 g), dimethylsulfoxide (100 mL), (7-carboxyheptyl)triphenylphosphonium bromide (39.95 g), benzophenone (18.2 g), and tetrahydrofuran (100 mL). The crude acid, isolated in the usual manner, required further purification by HPLC (hexane-ether; 3:2). The appropriate fractions were combined and evaporated and the residue was crystallized from hexane to provide 14.1 g of 9,9-diphenyl-8-nonenoic acid, mp 77.5°-78.5° C. Anal. Calculated for C21H24O2 : C, 81.78; H, 7.84. Found: C, 81.71; H, 7.70.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([NH:9][C:10]2[C:11]([NH:16][C:17]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[O:18])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][CH:4]=1.[I:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]2[C:11]([NH:16][C:17]([CH:19]3[CH2:20][CH2:21][N:22]([CH2:32][C:31]4[CH:34]=[CH:35][C:28]([I:27])=[CH:29][CH:30]=4)[CH2:23][CH2:24]3)=[O:18])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:25][CH:26]=1
Reactant: COc1ccc(C(=O)Nc2ccccc2NC(=O)C2CCNCC2)cc1
Reactant: O=Cc1ccc(I)cc1
Product: COc1ccc(C(=O)Nc2ccccc2NC(=O)C2CCN(Cc3ccc(I)cc3)CC2)cc1

Procedure:
Using the general procedure described in Example 3, N1-(4-methoxybenzoyl)-N2-(piperidin-4-ylcarbonyl)-1,2-benzenediamine (0.070 mmol) was reacted with 4-iodobenzaldehyde to provide 28 mg of the title product as the free base. Treatment with hydrochloric acid and concentration in vacuo yielded the salt of the title compound.
Reaction SMILES: C(O[C:4]([C:6]1[O:10][N:9]=[C:8](/[CH:11]=[CH:12]/[C:13]2[O:14][C:15]([N+:18]([O-:20])=[O:19])=[CH:16][CH:17]=2)[N:7]=1)=[O:5])C.[CH2:21]([NH:23][CH2:24][CH3:25])[CH3:22]>>[CH2:21]([N:23]([CH2:24][CH3:25])[C:4]([C:6]1[O:10][N:9]=[C:8](/[CH:11]=[CH:12]/[C:13]2[O:14][C:15]([N+:18]([O-:20])=[O:19])=[CH:16][CH:17]=2)[N:7]=1)=[O:5])[CH3:22]
Reactant: CCNCC
Reactant: CCOC(=O)c1nc(/C=C/c2ccc([N+](=O)[O-])o2)no1
Product: CCN(CC)C(=O)c1nc(/C=C/c2ccc([N+](=O)[O-])o2)no1
Yield: 57 %

Procedure:
trans-5-Ethoxycarbonyl-3-(5-nitrofur-2-ylvinyl)-1,2,4-oxadiazole (332 mg.) was heated under reflux with diethylamine (5 ml.) for 30 min. to give a deep red solution. Evaporation gave a red solid; recrystallisation from methanol (3 ml.) gave trans-5-diethylcarbamoyl-3-(5-nitrofur-2-ylvinyl)1,2,4-oxadiazole (208 mg., 57%), m.p. 118°-119°, λmax. (EtOH) 240 and 349 nm. (ε18,600 and 19,900), νmax. (CHBr3) 1665 (CONEt2), 1510, 1352 (NO2) and 960 cm.-1 (trans CH=CH).
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][NH:22][C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].[CH3:27][O:28][C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31]Cl>>[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][N:22]([CH2:31][C:30]5[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=5[O:28][CH3:27])[C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: COc1ccccc1CCl
Reactant: CC(C)N1CCC(Oc2ccc3c(c2)cc2n3CCNC2=O)CC1
Agent: [H-]
Agent: [Na+]
Product: COc1ccccc1CN1CCn2c(cc3cc(OC4CCN(C(C)C)CC4)ccc32)C1=O
Yield: 54 %

Procedure:
The title compound was synthesized in analogy to example 17, from 8-(1-isopropyl-piperidin-4-yloxy)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 1), sodium hydride and 2-methoxybenzyl chloride, to give the desired product as a white solid (54%).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]2[C:11](=[O:15])[NH:12][CH2:13][CH2:14][C:3]=12.[H-].[Na+].Cl.[Cl:19][CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>CN(C)C=O.O>[ClH:19].[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]2[C:11](=[O:15])[N:12]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[CH2:13][CH2:14][C:3]=12
Reactant: Cc1c2n(c3ccccc13)C(=O)NCC2
Reactant: ClCc1ccncc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1c2n(c3ccccc13)C(=O)N(Cc1ccncc1)CC2
Reaction time: 0.33 h

Procedure:
To a solution of 3,4-dihydro-5-methylpyrimido[1,6-a]-indol-1(2H)-one (188 mg) in N,N-dimethylformamide (3 ml) was added sodium hydride (60% in mineral oil, 88 mg) at 5° C. The mixture was stirred at the same temperature for 20 minutes. A solution of 4-chloromethylpyridine hydrochloride in N,N-dimethylformamide (3 ml) was added dropwise at 5° C. over five minutes. The reaction mixture was stirred at the same temperature for 30 minutes and at room temperature for 3 hours. The reaction mixture was diluted with chilled water and extract two times with 5%-methanol-chloroform. The extract was washed twice with water, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The residue was dissolved in 1N-hydrochloric acid (10 ml) and evaporated in vacuo. The residue was pulverized with acetone to give 3,4-dihydro-5-methyl-2-(4-pyridylmethyl)pyrimido[1,6-a]-indol-1(2H)-one hydrochloride (160 mg).