Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][CH:2]([F:14])[C:3]1[NH:7][C:6]2[CH:8]=[CH:9][CH:10]=[C:11]([O:12][CH3:13])[C:5]=2[N:4]=1.[Cl:15][C:16]1[N:21]=[C:20](Cl)[N:19]=[C:18]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)[N:17]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:15][C:16]1[N:21]=[C:20]([N:7]2[C:6]3[CH:8]=[CH:9][CH:10]=[C:11]([O:12][CH3:13])[C:5]=3[N:4]=[C:3]2[CH:2]([F:1])[F:14])[N:19]=[C:18]([N:23]2[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:27][CH2:28]2)[N:17]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2nc(Cl)nc(Cl)n2)CC1
Reactant: COc1cccc2[nH]c(C(F)F)nc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cccc2c1nc(C(F)F)n2-c1nc(Cl)nc(N2CCN(C(=O)OC(C)(C)C)CC2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 86.3 %

Procedure:
A mixture of 2-(difluoromethyl)-4-methoxy-1H-benzimidazole (0.99 g, 5 mmol), tert-butyl 4-(4,6-dichloro-1,3,5-triazin-2-yl)piperazine-1-carboxylate (Eur. J. Org. Chem. 2001, 2825-2839) (2.0 g, 6 mmol), and 3.5 g (25 mmol) powdered K2CO3 in 40 mL DMF was stirred at room temperature for 1 hr. Water was added and the product was collected by filtration and washed successively with water and cold ethanol to give 2.14 g (86% yield) of tert-butyl 4-{4-chloro-6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl}-1-piperazinecarboxylate: mp (CH2Cl2/EtOH)>300° C.; 1H NMR (CDCl3) δ7.99 (d, J=8.3 Hz, 1H), 7.48 (t, JHF=53.4 Hz, 1H), 7.41 (t, J=8.3 Hz, 1H), 6.87 (d, J=8.0 Hz, 1H), 4.06 (s, 3H), 3.95 (m, 4H), 3.58 (m, 4H), 1.50 (s, 9H); Anal. Calcd. for C21H24ClF2N7O3: C, 50.9; H, 4.9; N, 19.8. Found: C, 51.1; H, 4.9; N, 19.95%.
Reaction SMILES: [SH:1][CH2:2][CH2:3][CH2:4][Si:5]([O:10][CH3:11])([O:8][CH3:9])[O:6][CH3:7].[CH2:12]([NH:15][C:16]([NH2:18])=[O:17])[CH:13]=[CH2:14].CC(N=NC(C#N)(C)C)(C#N)C>>[Si:5]([CH2:4][CH2:3][CH2:2][S:1][CH2:14][CH2:13][CH2:12][NH:15][C:16]([NH2:18])=[O:17])([O:10][CH3:11])([O:6][CH3:7])[O:8][CH3:9]
Reactant: C=CCNC(N)=O
Reactant: CO[Si](CCCS)(OC)OC
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Product: CO[Si](CCCSCCCNC(N)=O)(OC)OC
Temperature: 90 °C

Procedure:
70 grams of mercaptopropyltrimethoxy silane and 35.5 gms. of allylurea were weighed into a flask equipped as in Example 1. The contents of the flask were heated to about 90° C. and 0.3 gm. of Vazo 64 was added. The temperature indicated an exotherm to about 145° C. which was controlled back down to about 100° C. for a total of 60 hours and it was then cooled. Titration of a sample showed about 71% reaction of the mercaptan. The material was filtered. The proton NMR analysis showed a structure consistent with the title compound. There was unreacted allylurea present at less than 25%.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].I[CH2:12][CH3:13]>>[Cl:1][C:2]1[C:9]([CH2:12][CH3:13])=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: CCI
Reactant: N#Cc1ccc(F)cc1Cl
Product: CCc1c(F)ccc(C#N)c1Cl
Yield: 28.2 %

Procedure:
The title compound is prepared by essentially following the procedure described in Preparation 1, using 2-chloro-4-fluoro-benzonitrile (12.2 g, 78.4 mmol), and iodoethane (18.4 g, 9.43 mL, 118 mmol). The crude product is purified on silica gel using 15-50% dichloromethane/hexanes to give the title compound as shiny white crystals (4.06 g, 28%). 1H-NMR (400 MHz, CDCl3) δ 7.54 (dd, J=5.6, 8.6 Hz, 1H), 7.07 (t, J=8.6 Hz, 1H), 2.85 (qd, J=7.5, 2.3 Hz, 2H), 1.19 (t, J=7.5 Hz, 3H).
Reaction SMILES: [O-]CC.[Na+].[Na].[O:6]([C:13]1[CH:14]=[C:15]([CH2:19][C:20]#[N:21])[CH:16]=[CH:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[N:22](OCCC(C)C)=[O:23]>C(O)C.C(OCC)C>[OH:23][N:22]=[C:19]([C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([O:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:14]=1)[C:20]#[N:21]
Reactant: N#CCc1cccc(Oc2ccccc2)c1
Reactant: CC(C)CCON=O
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Solvent: CCOCC
Product: N#CC(=NO)c1cccc(Oc2ccccc2)c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 45 %

Procedure:
To a solution of sodium ethoxide prepared from sodium (1.09 g) and ethanol (20 ml), a solution of 3-phenoxyphenylacetonitrile (8.30 g) in ethanol (15 ml) was added dropwise at 0° C., and then isoamyl nitrite (7.99 ml) was added dropwise. After stirring for 15 hours at room temperature, diethyl ether was added and the mixture was washed sequentially with 1N HCl, aqueous sodium bicarbonate and then saturated aqueous sodium chloride. The diethyl ether layer was dried (MgSO4), concentrated, and the residue was subjected to column chromatography on silica gel. The crystals obtained from a fraction eluted with ethyl acetate-hexane (1:4, v/v) were recrystallized with ethyl acetate-hexane to obtain 2-hydroxyimino-2-(3-phenoxyphenyl)acetonitrile (4.25 g, yield: 45%) as pale-yellow crystals. A mixture of the E- form and the Z- form. m.p. 124-125° C.
Reaction SMILES: O=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:4][C:3]1=2.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][CH2:25][NH2:26].[BH4-].[Na+].O>C(O)C>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][CH2:25][NH:26][CH:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:4][C:3]1=2
Reactant: COC(=O)c1ccc2c(c1)CCCC2=O
Reactant: COc1ccccc1CCN
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COC(=O)c1ccc2c(c1)CCCC2NCCc1ccccc1OC
Temperature: 25 °C
Reaction time: 24 h

Procedure:
15.2 g (74.5 mmol) of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate [U. Gerlach and T. Wollmann, Tetrahedron Lett. 1992, 33 (38), 5499-5502] and 11.5 g (74.5 mmol) of 2-(2-methoxyphenyl)ethylamine in 50 ml of ethanol were heated under reflux for 2 h. The mixture was then concentrated to dryness under reduced pressure, the residue was taken up in 300 ml of methanol and 5.6 g (149 mmol) of sodium borohydride were, over 20 min, added a little at a time at RT with slight external cooling to the suspension. The brownish solution was stirred at RT for 24 h and then poured into 900 ml of water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and concentrated. The residue (24.5 g) was purified by flash chromatography on silica gel using the mobile phase cyclohexane/ethyl acetate 2:1.
Reaction SMILES: [CH:1]([O:4][C:5](=[O:29])[CH:6]([NH2:28])[CH:7]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:18]=2)[NH:13][CH:12]=1)[CH2:8][O:9][CH3:10])([CH3:3])[CH3:2].[CH2:30]=O>C1(C)C(C)=CC=CC=1>[CH:1]([O:4][C:5]([CH:6]1[CH:7]([CH2:8][O:9][CH3:10])[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:18]=3)[NH:13][C:12]=2[CH2:30][NH:28]1)=[O:29])([CH3:3])[CH3:2]
Reactant: COCC(c1c[nH]c2ccc(OCc3ccccc3)cc12)C(N)C(=O)OC(C)C
Reactant: C=O
Solvent: Cc1ccccc1C
Product: COCC1c2c([nH]c3ccc(OCc4ccccc4)cc23)CNC1C(=O)OC(C)C
Yield: 61.2 %

Procedure:
A solution is prepared from 3.8 g of 2-amino-3-(5-benzyloxyindol-3-yl)-4-methoxybutyric acid isopropyl ester (10 mmol) in 80 ml of xylene and added dropwise to a suspension of 360 mg of paraformaldehyde in 60 ml of xylene heated for 45 minutes to 100° C. The mixture is then refluxed for 2 hours on a water trap. After concentration, the residue is chromatographed over silica gel with methylene chloride:acetone=1:1 as the eluent, yielding 2.5 g of 6-benzyloxy-4-methoxymethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid isopropyl ester (65% yield as an oil); or a suspension of 2.56 g of paraformaldehyde in 8 ml of water and 0.8 ml of concentrated hydrochloric acid is refluxed at 80° C. for 1 hour. One-tenth of the thus-obtained clear solution is added dropwise, after cooling to room temperature, to a solution of 3.8 g (10 mmol) of 2-amino-3-(5-benzyloxyindol-3 -yl)-4-methoxybutyric acid isopropyl ester in 500 ml of water and 10 ml of concentrated hydrochloric acid (pH=3). After 1/2 hour of agitation, an estimate of the amount of amino compound still remaining is made by thin-layer chromatography, and a corresponding quantity of formaldehyde solution is added. Thereupon, the mixture is stirred for another hour and then extracted twice by shaking with 50 ml of toluene, respectively. The organic phase is discarded. The aqueous phase is adjusted, after adding 100 ml of toluene, to a pH of 5.3 with 27% strength sodium hydroxide solution. After extraction by shaking, the mixture is additionally extracted by shaking twice with 50 ml of toluene; these 3 organic phases are combined, dried over sodium sulfate, filtered, and concentrated, thus obtaining 3.3 g (85%) of 6-benzyloxy-4-methoxymethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid isopropyl ester as an oil.
Reaction SMILES: [ClH:1].C(OCC)(=O)C.[C:8]([O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][N:22]1[C:30]2[C:29]([NH:31][C:32]3[CH:51]=[CH:50][C:35]([O:36][CH:37]4[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38]4)=[C:34]([Cl:52])[CH:33]=3)=[N:28][CH:27]=[N:26][C:25]=2[CH:24]=[CH:23]1)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(O)C>[ClH:52].[ClH:1].[C:8]([O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][N:22]1[C:30]2[C:29]([NH:31][C:32]3[CH:51]=[CH:50][C:35]([O:36][CH:37]4[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]4)=[C:34]([Cl:52])[CH:33]=3)=[N:28][CH:27]=[N:26][C:25]=2[CH:24]=[CH:23]1)(=[O:15])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(Nc3ncnc4ccn(CCOCCOC(=O)c5ccccc5)c34)cc2Cl)CC1
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: O=C(OCCOCCn1ccc2ncnc(Nc3ccc(OC4CCNCC4)c(Cl)c3)c21)c1ccccc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
4N Hydrochloric acid/ethyl acetate solution (20 mL) and ethanol (10 mL) were added to tert-butyl 4-{4-[(5-{2-[2-(benzoyloxy)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino]-2-chlorophenoxy}piperidine-1-carboxylate (3.82 g), and the mixture was stirred at room temperature for 5 hrs. The reaction mixture was concentrated under reduced pressure, and the obtained residue was crystallized from ethanol-ethyl acetate to give the title compound (3.68 g) as a white powder.
Reaction SMILES: [Cl:1][CH2:2][CH:3]([N:6]=[C:7](Cl)[CH3:8])[CH2:4][CH3:5].C(=O)([O-])[O-:11].[Na+].[Na+]>>[Cl:1][CH2:2][CH:3]([NH:6][C:7](=[O:11])[CH3:8])[CH2:4][CH3:5]
Reactant: O=C([O-])[O-]
Reactant: CCC(CCl)N=C(C)Cl
Agent: [Na+]
Product: CCC(CCl)NC(C)=O

Procedure:
A sample of N-[1-(chloromethyl)propyl]acetimidoyl chloride from Example 8 is treated with an excess of 10% aqueous sodium carbonate solution at room temperature. The organic material is extracted with ether and dried over MgSO4. Removal of the solvent under reduced pressure leaves N-[1-(chloromethyl)propyl]acetamide as a crystalline solid in nearly quantitative yield. An infrared spectrum shows peaks at 3300(M), 3100(W), 1650(S), and 550(S) cm-1 ; nuclear magnetic resonance (CDCl3) shows peaks 0.95 ppm (t ,3H), 1.4-1.8 ppm (m ,2H), 2.03 ppm (s ,3H), 3.67 ppm (d,2H,CH2Cl), 3.8-4.4 ppm (m ,1H).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C@@H:4](/[CH:5]=[C:6](\[Cl:12])/[C:7](=[O:11])[O:8][CH2:9][CH3:10])[C@H:3]1[C:13]([OH:15])=[O:14].[C:17]([C@@H:19](O)[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:21]=1)#[N:18]>C(Cl)(Cl)Cl>[CH3:16][C:2]1([CH3:1])[C@@H:4](/[CH:5]=[C:6](\[Cl:12])/[C:7](=[O:11])[O:8][CH2:9][CH3:10])[C@H:3]1[C:13]([O:15][C@H:19]([C:17]#[N:18])[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:21]=1)=[O:14]
Reactant: N#C[C@@H](O)c1cccc(Oc2ccccc2)c1
Reactant: CCOC(=O)/C(Cl)=C/[C@H]1[C@@H](C(=O)O)C1(C)C
Solvent: ClC(Cl)Cl
Product: CCOC(=O)/C(Cl)=C/[C@H]1[C@@H](C(=O)O[C@H](C#N)c2cccc(Oc3ccccc3)c2)C1(C)C

Procedure:
Using the procedure of Example 1, (1R,cis) 2,2-dimethyl-3(Z)-[2-chloro-3-oxo-3-ethoxy-propenyl]-cyclopropane-1-carboxylic acid and (S)α-cyano-3-phenoxy-benzyl alcohol were reacted to obtain (S)α-cyano-3-phenoxybenzyl (1R,cis) 2,2-dimethyl-3(Z)-[2-chloro-3-oxo-3-ethoxy-propenyl]-cyclopropane-1-carboxylate with a specific rotation of [α]D20 =+21.5°±2.5° (c=0.3% in chloroform).
Reaction SMILES: [B-](F)(F)(F)F.[B-](F)(F)(F)F.C1[N+]2([CH2:19][Cl:20])CC[N+](F)(CC2)C1.[Cl-].[Na+].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([C:32](=[O:34])[CH3:33])C=[CH:30][CH:31]=1>C(#N)C>[Cl:20][C:19]1[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][C:28]=1[C:32](=[O:34])[CH3:33]
Reactant: COc1cccc(C(C)=O)c1
Reactant: F[N+]12CC[N+](CCl)(CC1)CC2
Agent: F[B-](F)(F)F
Agent: [Cl-]
Agent: [Na+]
Solvent: CC#N
Product: COc1ccc(Cl)c(C(C)=O)c1
Temperature: 25 °C
Reaction time: 120 h

Procedure:
To a solution of SELECTFLUOR™(5.0 g, 14.1 mmol) and sodium chloride (825 mg, 14.1 mmol) in acetonitrile (200 ml), under nitrogen, was added 1-(3-methoxyphenyl)ethanone (1.94 ml, 14.1 mmol) and the reaction mixture was stirred at room temperature for 5 days. To the mixture was added distilled water (200 ml) and the solution was extracted with dichloromethane (2×100 ml). The combined extracts were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (silica) with gradient elution, ethyl acetate:cyclohexane [5:95 to 10:90]. The appropriate fractions were combined and concentrated to give the title compound (1.12 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:10](I)[C:3]=12.[N:15]1([C:20]2[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:10]([C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([N:15]4[CH2:16][CH2:17][CH2:18][CH2:19]4)[CH:21]=3)[C:3]=12
Reactant: CC(C)n1cc(I)c2c(Br)ccnc21
Reactant: OB(O)c1cccc(N2CCCC2)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: CC(C)n1cc(-c2cccc(N3CCCC3)c2)c2c(Br)ccnc21
Temperature: 65 °C
Yield: 23.5 %

Procedure:
A mixture of 4-bromo-3-iodo-1-isopropyl-1H-pyrrolo[2,3-b]pyridine (D10) (2.80 g, 7.67 mmol), (3-(pyrrolidin-1-yl)phenyl)boronic acid (1.612 g, 8.44 mmol), bis(triphenylphosphine)palladium(II) chloride (0.538 g, 0.767 mmol) and 2M sodium carbonate aqueous solution (9.59 mL, 19.18 mmol) in ACN (35.0 mL) was heated at 65° C. for 2 hours and then allowed to cool to RT. The mixture was evaporated to dryness and the residue partitioned between water (50 mL) and ethyl acetate (150 mL). The aqueous phase was separated and extracted with additional ethyl acetate (100 mL). The organic extracts were combined, washed with brine (50 mL), dried with anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was purified on silica eluting with cyclohexane and ethyl acetate (0-35%) to give an impure material which was further purified on silica eluting with cyclohexane and ethyl acetate (0-25%). The appropriate fractions were combined and evaporated to dryness producing the title compound (692 mg). LCMS (A): m/z (M+H)+ 384/386, C20H22BrN3 requires 383/385 (acidic).
Reaction SMILES: [CH:1]1([C:6]([O:8][CH3:9])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.Br.Br[CH2:20][CH2:21][N:22]([CH2:25][CH3:26])[CH2:23][CH3:24]>C1COCC1.O>[CH2:21]([N:22]([CH2:25][CH3:26])[CH2:23][CH2:24][C:1]1([C:6]([O:8][CH3:9])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1)[CH3:20]
Reactant: COC(=O)C1CCCC1
Reactant: CCN(CC)CCBr
Agent: Br
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CCN(CC)CCC1(C(=O)OC)CCCC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 79 %

Procedure:
To methyl cyclopentanecarboxylate (1 g) in THF (8 ml) at −61° C. is added a solution of 2M LDA (9.8 ml). The mixture is stirred at room temperature for 15 minutes, then 2-bromo-N,N-diethylethanamine hydrobromide (2.04 g) is added at −61° C. The mixture is stirred for 5 minutes at this temperature, then at room temperature. The solution became yellow and was diluted with water (30 ml). The organic phase is extracted twice with a brine solution (30 ml). The pH of the organic phase is adjusted to 4 with 6N HCl. After decantation, the aqueous phase is extracted with CH2Cl2 (20 ml) and the pH of aqueous phase adjusted to 12 with 6 N NaOH. After decantation, the organic phase is dried over MgSO4 and concentrated. The residue is treated with diethyl ether (10 ml) and the white solid is filtrated. Methyl 1-[2-(diethylamino)ethyl]cyclopentanecarboxylate 280 is obtained as a yellow liquid after concentration of the ether solution.
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1.S(Cl)([Cl:23])=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:23][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1
Reactant: O=S(Cl)Cl
Reactant: CN1C(=O)CCc2cc(-c3cncc(CO)c3)ccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CN1C(=O)CCc2cc(-c3cncc(CCl)c3)ccc21
Temperature: 3.5 °C
Reaction time: 2 h
Yield: 94.7 %

Procedure:
At 0° C., 6-(5-hydroxymethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one (190 mg, 0.7 mmol) in DCM (15 mL) was treated slowly with thionyl chloride (0.32 mL, 4.0 mmol). After the addition, the reaction mixture was allowed to stir at 2-5° C. for 2 hours before it was poured into satd. aq. NaHCO3 solution (50 mL). After extraction with EtOAc, the organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give title compound (190 mg, 93.5%) as yellow oil. MS: 287.1 (M+H+).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[OH:5][CH:6]([CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH3:34])[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][CH2:16][NH:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[CH2:10][CH2:9]1.[OH-].[K+]>C1(C)C=CC=CC=1>[OH:5][CH:6]([CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH3:34])[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:15][CH2:16][N:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:1]2=[O:2])[CH2:10][CH2:9]1
Reactant: O=C(Cl)Cl
Reactant: COc1ccccc1OCC(O)CN1CCC(NCCNc2ccc(Cl)cc2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: COc1ccccc1OCC(O)CN1CCC(N2CCN(c3ccc(Cl)cc3)C2=O)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
With vigorous stirring, 630 ml of a 20% solution of phosgene in toluene are added dropwise at a reaction temperature of 5° to 10° C. in the course of 13/4 hours to an emulsion of 56 g of 1-[2-hydroxy-3-(2-methoxyphenyloxy)-propyl]-4-[2-(4-chloroanilino)-ethylamino]-piperidine in 340 ml of toluene and 200 ml of a 3 N potassium hydroxide solution. Thereafter 193 ml of a 6 N aqueous potassium hydroxide solution are added dropwise at the same reaction temperature in the course of half an hour. The reaction mixture is further stirred for 1 hour at 5° to 10° C. and for 20 hours at room temperature and then concentrated. The residue is made alkaline with a 2 N aqueous sodium hydroxide solution and extracted with five 100 ml portions of methylene chloride. The extracts are dried over sodium sulphate and concentrated under reduced pressure. The residue is dissolved in methanol and boiled for 30 minutes with the addition of activated charcoal. The batch is filtered and the filtrate is concentrated under reduced pressure. The residue is treated with toluene and recrystallised from isopropanol to yield 1-{1-[2-hydroxy-3-(2-methoxyphenyloxy)-propyl]-4-piperidyl}-3-(4-chlorophenyl)-imidazolidin-2-one with a melting point of 136°-137° C.
Reaction SMILES: [C:1]1([C:7]2([OH:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:18][CH2:19][CH2:20][CH2:21][OH:22].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C(C)=CC=CC=1>[OH:22][CH2:21][CH2:20][CH2:19][NH:18][C:8]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([OH:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1
Reactant: O=C1Nc2ccccc2C1(O)c1ccccc1
Reactant: NCCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1C
Product: OCCCNC1=Nc2ccccc2C1(O)c1ccccc1

Procedure:
3-Phenyl-3-hydroxy-3H-indol-2-one (4.5 g.) was heated under reflux with 3-aminopropanol (6.0 g.) in xylene (100 ml.) and toluene-p-sulphonic acid (150 mg) in an apparatus fitted with a water separator. After 24 hours the reaction mixture was cooled. The product crystallised and was filtered off and recrystallised from methanol to give the title compound, 3.81 g., m.p. 215°-217°C. (Found C, 72.4; H, 6.7; N. 9.9, C17H18N2O2 requires C, 72.3; H, 6.4; N, 9.9%).
Reaction SMILES: [BH4-].[Na+].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=[O:12])[CH3:11]>CO>[OH:12][CH:10]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[NH2:3])[CH3:11]
Reactant: CC(=O)c1ccccc1N
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(O)c1ccccc1N
Yield: 64 %

Procedure:
Sodium borohydride (40 g, 1.0 mol) was added portion wise to a stirred solution of o-aminoacetophenone (80 g) in methanol (800 ml) at 0°, allowing the effervescence to subside between each addition. Cooling was removed and the mixture allowed to warm to reflux temperature to complete the reaction. When cool, the solvent was evaporated and the residue partioned between dichloromethane-water. The organic solution was washed successively with water and brine, dried (anhyd. MgSO4), filtered and evaporated to a light yellow oil which crystallized from petroleum spirit (40°-60°) to give white crystals (52 g, 64%), m.p. 50°-52°.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[C:15]([O:22][CH3:23])[CH:14]=2)=[O:12])[N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.[CH3:24][N:25](C)C=O>[C-]#N.[Zn+2].[C-]#N.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>[CH3:23][O:22][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[N+:19]([O-:21])=[O:20])[C:11]([C:4]1[N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]2=[C:2]([C:24]#[N:25])[N:3]=1)=[O:12]
Reactant: CN(C)C=O
Reactant: COc1cc(C(=O)c2nc(Br)c3ccccn23)ccc1[N+](=O)[O-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: COc1cc(C(=O)c2nc(C#N)c3ccccn23)ccc1[N+](=O)[O-]
Temperature: 90 °C

Procedure:
2.17 g (18.48 mmol) of zinc cyanide and then 1.07 g (0.93 mmol) of tetrakis(triphenylphosphine)palladium(0) are added under a nitrogen atmosphere to 6.94 g (18.45 mmol) of (1-bromoimidazo[1,5-a]pyridin-3-yl)(3-methoxy-4-nitrophenyl)methanone obtained in example 20 in 160 ml of N,N-dimethylformamide. The reaction medium is heated at 90° C. for 17 h. The precipitate obtained is filtered off, washed with water, then with a saturated aqueous sodium bicarbonate solution and with water. After drying, 5.9 g of a yellow solid are collected. Melting point: 219° C.; 1H NMR (d6-DMSO): 4.01 (3H, s), 7.53-7.55 (1H, m), 7.76-7.81 (1H, m), 7.95-8.01 (2H, m), 8.08 (1H, d), 8.19 (1H, d), 9.70 (1H, d)
Reaction SMILES: [C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])(=[O:4])[CH2:2][CH3:3].[C:15]1(=[O:21])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>>[OH:21][C:15]1([CH:2]([CH3:3])[C:1]([N:5]2[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[O:7][C:6]2=[O:14])=[O:4])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: CCC(=O)n1c(=O)oc2ccccc21
Reactant: O=C1CCCCC1
Product: CC(C(=O)n1c(=O)oc2ccccc21)C1(O)CCCCC1

Procedure:
Prepared according to the method of paragraph C by reaction of N-propionyl-2-benzoxazolone with cyclohexanone; mp 58–9° C. 1H NMR (CDCl3): δ 8.09 (m, 1 H); 7.25 (m, 3 H); 4.11 (q, 1 H, J=7 Hz); 2.90 (br s, 1 H); 1.82 (br d, 1 H, J=13 Hz); 1.59 (m, 8 H); 1.34 (d, 3 H, J=7 Hz); 1.23 (m, 1 H). 13C NMR (CDCl3): δ 177.20, 151.42, 142.03, 127.69, 125.55, 124.91, 116.38, 109.88, 72.89, 46.77, 37.03, 33.37, 25.64, 21.73, 21.40, 12.16.