Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:24]=[CH:23][CH:22]=[CH:21][C:5]=1[CH2:6][NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)([O-])=O>CO>[NH2:1][C:4]1[CH:24]=[CH:23][CH:22]=[CH:21][C:5]=1[CH2:6][NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:15])[CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCC(NCc2ccccc2[N+](=O)[O-])CC1
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(NCc2ccccc2N)CC1

Procedure:
A solution of tert-Butyl 4-(2-nitrobenzylamino)piperidine-1-carboxylate (24 g, 71.6 mmol) in MeOH (150 ml) was stirred under an atmosphere of hydrogen for 24 hours. The reaction mixture was filtered and evaporated to give the crude amine, which was used without further purification.
Reaction SMILES: [CH:1]1([C:9]([OH:11])=O)[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)[CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:25][CH2:26][C:27]([NH2:29])=[O:28].CCCCCCC>C(OCC)(=O)C.O>[NH2:29][C:27](=[O:28])[CH2:26][NH:25][C:9]([CH:1]1[C:3]2([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:2]1)=[O:11]
Reactant: O=C(O)C1CC12CCCCC2
Reactant: NCC(N)=O
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Solvent: O
Product: NC(=O)CNC(=O)C1CC12CCCCC2
Temperature: 65 °C
Reaction time: 2 h

Procedure:
The product from Example 1B (420 g, 2.72 mol) and 1,1′-carbonyldiimidazole (530 g, 3.27 mol) were combined in ethyl acetate (8.9 Kg) at ambient temperature and stirred for 2 hours. The mixture was treated with water (50 mL) and 2-aminoacetamide hydrochloride (368 g, 3.27 mol, purchased from Aldrich), heated at 65° C. for 10 hours, allowed to cool to room temperature, diluted with H2O (4.9 Kg) and heptane (1.35 Kg), and cooled to 10° C. resulting in formation of a solid. The solid was collected by filtration and washed with a mixture of H2O (440 g) and ethyl acetate (350 g). The resulting wet cake was slurried with H2O (2.0 Kg), filtered (550 g heptane wash) and dried to afford the title compound. 1H NMR (d6-DMSO, 300 MHz) δ 8.10 (t, 1H), 7.21 (s, 1H), 6.95 (s, 1H), 3.62 (dq, 2H), 1.1-1.6 (m, 11H), 0.85 (dd, 1H), 0.61 (dd, 1H); 13C NMR (CDCl3, 100 MHz) δ 171.2, 170.8, 42.0, 36.9, 28.2, 26.7, 25.8, 25.2, 18.1; MS m/z 211 (M+H)+.
Reaction SMILES: ClC1C=CC=CC=1[NH:8][CH2:9][C:10]([OH:12])=[O:11].[Cl:13][C:14]1[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=1[CH:16]([NH:19][CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:17]#[N:18].[Cl:37][C:38]1[CH:45]=[C:44]([Cl:46])[CH:43]=[C:40]([CH:41]=[O:42])[C:39]=1[OH:47].[NH2:48][C@H:49]([C:54]([OH:56])=[O:55])[C:50]([CH3:53])([CH3:52])[CH3:51].[C:57]([O:61][C@H:62]([CH3:68])[C@@H:63]([C:65]([OH:67])=[O:66])[NH2:64])([CH3:60])([CH3:59])[CH3:58].NCC(O)=O.C[Si](C#N)(C)C>C1(C)C=CC=CC=1.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CCOCC>[Cl:37][C:38]1[CH:45]=[C:44]([Cl:46])[CH:43]=[C:40]([CH:41]=[O:42])[C:39]=1[OH:47].[NH2:48][C@H:49]([C:54]([OH:56])=[O:55])[C:50]([CH3:53])([CH3:52])[CH3:51].[C:57]([O:61][C@H:62]([CH3:68])[C@@H:63]([C:65]([OH:67])=[O:66])[NH2:64])([CH3:60])([CH3:58])[CH3:59].[CH3:14][O:12][C:10](=[O:11])[CH2:9][NH2:8].[Cl:13][C:14]1[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=1[CH:16]([NH:19][CH:20]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:17]#[N:18]
Reactant: O=C(O)CNc1ccccc1Cl
Agent: [Ti+4]
Agent: CC(C)(C)[C@H](N)C(=O)O
Agent: CC(C)[O-]
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: COC(=O)CN
Reaction time: 0.25 h

Procedure:
The following is an example of a solution phase catalyzed reaction to synthesize 2-chlorophenyl glycine. Screening of the above library determined that a preferred catalyst for the formation of N-(2-chloro-a-cyanobenzyl)benzhydrylamine was 3,5-Dichlorosalicylaldehyde-tert-Leucine-(O-tert-Butyl)Threonine-Glycine. 3,5-Dichlorosalicylaldehyde-tert-Leucine-(O-tert-Butyl)Threonine-Glycine methyl ester was synthesized using standard solid-phase synthesis techniques and was added (53.3 mg, 0.1 mmol) under a nitrogen atmosphere to a solution of titanium tetraisopropoxide (29.5 ul, 0.1 mmol) in toluene (2 ml), and the mixture was stirred for about 15 minutes. Ortho-chlorobenzylidenylbenzhydrylamine (306 mg, 1.0 mmol) was added and the mixture stirred until complete dissolution of the substrate (ca. 10 minutes). Trimethylsilylcyanide (267 ul, 2.0 mmol) was added to the solution and the resultant mixture was stirred for 48 hours. Addition of ether (2 ml, 5% water) followed by filtration through silica afforded a product that was predominantly the desired isomer contaminated with a small amount of starting material. Addition of hexanes to the ethereal solution afforded pure N-(2-chloro-a-cyanobenzyl)benzhydrylamine as white crystals. Analysis by HPLC indicated optical purity of >99%.
Reaction SMILES: [CH3:1][C:2]1([CH2:14][C:15]([OH:17])=O)[C:6](=[O:7])[N:5](CC(F)(F)F)[C:4](=[O:13])[NH:3]1.[C:18]1([C:24]2[CH:37]=[CH:36][C:27]3[N:28]=[C:29]([CH2:31][C:32]([NH:34][NH2:35])=O)[S:30][C:26]=3[CH:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC.CCN(C(C)C)C(C)C>O1CCOCC1.C(Cl)Cl>[CH3:1][C:2]1([CH2:14][C:15]2[O:17][C:32]([CH2:31][C:29]3[S:30][C:26]4[CH:25]=[C:24]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[CH:37]=[CH:36][C:27]=4[N:28]=3)=[N:34][N:35]=2)[NH:3][C:4](=[O:13])[NH:5][C:6]1=[O:7]
Reactant: CC1(CC(=O)O)NC(=O)N(CC(F)(F)F)C1=O
Reactant: NNC(=O)Cc1nc2ccc(-c3ccccc3)cc2s1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: C1COCCO1
Product: CC1(Cc2nnc(Cc3nc4ccc(-c5ccccc5)cc4s3)o2)NC(=O)NC1=O
Temperature: 90 °C
Reaction time: 3 h
Yield: 84.7 %

Procedure:
To a solution of Compound 31b (613 mg, 2.22 mmol) in dioxane (10 mL) was added 2-(6-phenylbenzo[d]thiazol-2-yl)acetohydrazide (723 mg, 2.22 mmol), (described in WO 2011/074560), 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (3.30 mL, 5.55 mmol) and DIPEA (1.0 mL, 5.55 mmol). The reaction mixture was stirred at 90° C. for 3 h. 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% in EtOAc) (3.30 mL, 5.55 mmol) and DIPEA (1.0 mL, 5.55 mmol) were added. The reaction mixture was heated at 90° C. for 14 h. The reaction mixture was diluted with DCM, and the solution washed with 1.5 M potassium phosphate solution and 1.0 M HCl and brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give the crude residue. The crude residue was dissolved in DCM, loaded on CELITE, charged to a 80 g silica gel cartridge which was eluted with a 40 min gradient from 0-10% MeOH/DCM to give racemic 5-methyl-5-((5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)methyl)imidazolidine-2,4-dione (943 mg, 1.88 mmol, 85% yield) as a brown solid. The enantiomers were separated by SFC separation (Berger Prep SFC; column: Lux Cellulose-4, 30×250 mm ID, 5 μm; Flow rate: 100 mL/min, 150 bar BP, 40° C.; Mobile Phase: 25% Isopropanol/75% CO2; Wavelength: 220 nm) to afford Isomer A as Compound 31c (414 mg, 0.817 mmol, 36.8%). LCMS=2.0 min using analytical method (B), 502.1 (M+H). Analytical SFC RT=7.8 min (Instrument, Berger SFC; Column: Lux Cellulose-4, 4.6×250 mm ID, 5 μm; Flow rate: 3 mL/min, 150 bar BP, 35° C.; Mobile Phase: 20% Isopropanol/80% CO2; 220 nm). 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 8.43 (d, J=1.5 Hz, 1H), 8.05 (d, J=8.5 Hz, 1H), 7.83 (dd, J=8.5, 1.8 Hz, 1H), 7.78-7.68 (m, 2H), 7.54-7.46 (m, 2H), 7.44-7.34 (m, 1H), 4.86 (d, J=1.3 Hz, 2H), 4.10 (q, J=9.2 Hz, 2H), 3.34 (t, J=15.6 Hz, 2H), 1.46 (s, 3H) and Isomer B (Rt=12.8 min, 45 mg, 13% yield), LCMS=1.77 min using analytical method (B), 440.9 (M+H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])=[C:10](Cl)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[NH:26]([CH3:28])[CH3:27]>CS(C)=O>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])=[C:10]([N:26]([CH3:28])[CH3:27])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)c(-c2ccccc2F)cc1[N+](=O)[O-]
Reactant: CNC
Solvent: CS(C)=O
Product: CN(C)c1cc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])cc1-c1ccccc1F

Procedure:
The title compound was prepared from (2-chloro-2′-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example D3) (9.568 g, ca. 26 mmol) and Me2NH (60% in H2O, 12 mL) in DMSO (87 mL) at 23° C. according to the general procedure C. Obtained as a yellow solid (4.54 g).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([NH:12][NH:13][C:14](N)=[O:15])(N)=[O:10].Cl>CN1CCCC1=O>[CH2:1]([N:8]1[C:14](=[O:15])[NH:13][NH:12][C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC(=O)NNC(N)=O
Reactant: NCc1ccccc1
Agent: Cl
Solvent: CN1CCCC1=O
Product: O=c1[nH][nH]c(=O)n1Cc1ccccc1

Procedure:
53.5 g of benzylamine and 59 g of hydrazodicarbonamide are stirred in 100 ml of N-methyl pyrrolidone for 4 hours at 175° C. and for 5 hours at 200° C. The solvent is then distilled off in vacuo, the residue is triturated with 50 ml of a 10% sodium hydroxide solution and the residue is isolated by filtration under suction. The filtrate is neutralised with 10% hydrochloric acid. A deposit is formed which is filtered off under suction and washed with water, giving 67 g (70% of the theoretical yield) of 4-benzyl-1,2,4-triazolidine-3,5-dione in the form of colourless crystals melting at 185° to 188° C. (CH3CN).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](Cl)=[O:8])([O-:3])=[O:2].[C:13]1([O:19][CH3:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Cl-].[Al+3].[Cl-].[Cl-].C(OCC)(=O)C>ClCCl.O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([C:16]1[CH:17]=[CH:18][C:13]([O:19][CH3:20])=[CH:14][CH:15]=1)=[O:8])([O-:3])=[O:2]
Reactant: COc1ccccc1
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Solvent: CCOC(C)=O
Product: COc1ccc(C(=O)c2cccc([N+](=O)[O-])c2)cc1

Procedure:
A mixture of 3-nitrobenzoyl chloride (3.71 g), anisole (2.0 ml) and aluminum chloride (2.67 g) in dichloromethane (50 ml) was refluxed for 1 hour. The reaction mixture was poured into a mixture of ethyl acetate and water. The organic phase was washed with brine, dried over magnesium sulfate and concentrated. The resultant solid was collected and washed with ethyl acetate to give 1-(3-nitrobenzoyl)-4-methoxybenzene (955 mg).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([O:15]CC)=[O:14])=[CH:7][C:6]=1[NH:18][C:19](=[O:37])[CH2:20][CH:21]([C:27]1[C:32]([O:33][CH3:34])=[CH:31][CH:30]=[CH:29][C:28]=1[O:35][CH3:36])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.CCCCCC>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:7][C:6]=1[NH:18][C:19](=[O:37])[CH2:20][CH:21]([C:27]1[C:28]([O:35][CH3:36])=[CH:29][CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCCCC(CC(=O)Nc1cc(CCC(=O)OCC)ccc1C(C)(C)C)c1c(OC)cccc1OC
Solvent: ClCCl
Solvent: CCCCCC
Product: CCCCCC(CC(=O)Nc1cc(CCC(=O)O)ccc1C(C)(C)C)c1c(OC)cccc1OC

Procedure:
Following a similar procedure to that described in Preparation 77, but using N-[2-t-butyl-5-(2-carboethoxyethyl)phenyl]-3-(2,6-dimethoxyphenyl)octanamide (prepared as described in Preparation 86), the title compound was obtained as colorless crystals, melting at 52°-53° C. (from methylene chloride-hexane).
Reaction SMILES: C1(P(=[N:20][C:21]2[C:22](/[CH:27]=[CH:28]/[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[N:23][CH:24]=[CH:25][CH:26]=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:36][C:37]([F:48])([F:47])[C:38]1[CH:39]=[C:40]([N:44]=[C:45]=O)[CH:41]=[CH:42][CH:43]=1>>[F:36][C:37]([F:47])([F:48])[C:38]1[CH:39]=[C:40]([N:44]=[C:45]=[N:20][C:21]2[C:22](/[CH:27]=[CH:28]/[C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])=[N:23][CH:24]=[CH:25][CH:26]=2)[CH:41]=[CH:42][CH:43]=1
Reactant: O=C=Nc1cccc(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)/C=C/c1ncccc1N=P(c1ccccc1)(c1ccccc1)c1ccccc1
Product: CC(C)(C)OC(=O)/C=C/c1ncccc1N=C=Nc1cccc(C(F)(F)F)c1

Procedure:
65 mg (0.14 mmol) of iminophosphorane from Example 11A are reacted by general procedure [B] with 27 mg (0.14 mmol) of 3-trifluoromethylphenyl isocyanate, and the crude product is reacted further without purification.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][C:20]2[C:23]3[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=3[O:25][C:19]=2[CH2:18]1)(O)=[O:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C1COCC1>[OH:2][CH2:1][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][C:20]2[C:23]3[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=3[O:25][C:19]=2[CH2:18]1
Reactant: O=C(O)c1ccc2[nH]cc(CCCCN3CCc4c(oc5ccccc45)C3)c2c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1ccc2[nH]cc(CCCCN3CCc4c(oc5ccccc45)C3)c2c1
Reaction time: 2 h

Procedure:
A solution of 3.88 g of 2-[4-(5-carboxy-3-indolyl)butyl]-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine in 40 ml of THF is added dropwise to a stirred suspension of 0.76 g of lithium aluminium hydride in 30 ml of THF under N2. The mixture is then stirred at 20° for 2 hours, decomposition is carried out with dilute sodium hydroxide solution and then with water, and the mixture is filtered. The usual working up is carried out on the filtrate. 2-[4-(5-Hydroxymethyl-3-indolyl)butyl]-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine is obtained.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:17][C:18]([F:21])([F:20])[F:19])[C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([C:13]([F:16])([F:15])[F:14])[CH:6]=1.[F:22][C:23]1[N:28]=[CH:27][C:26](O)=[CH:25][CH:24]=1>>[F:22][C:23]1[N:28]=[CH:27][C:26]([O:1][CH2:2][CH2:3][N:4]([CH2:17][C:18]([F:19])([F:20])[F:21])[C:5]2[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([C:13]([F:15])([F:16])[F:14])[CH:6]=2)=[CH:25][CH:24]=1
Reactant: Oc1ccc(F)nc1
Reactant: N#Cc1ccc(N(CCO)CC(F)(F)F)cc1C(F)(F)F
Product: N#Cc1ccc(N(CCOc2ccc(F)nc2)CC(F)(F)F)cc1C(F)(F)F

Procedure:
Synthesized as described in Example 27B from 4-[(2-hydroxyethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile (Example 15B) and 6-fluoro-3-pyridinol (step A above): MS (ESI) m/z 408 (M+1).
Reaction SMILES: [O:1]=[C:2](Cl)[O:3][C:4]([Cl:7])([Cl:6])[Cl:5].[CH2:9]([O:16][NH:17][C@H:18]1[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:20]([C:30]([O:32][CH2:33][CH:34]=[CH2:35])=[O:31])[CH2:19]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)CC)C>ClCCl>[CH2:9]([O:16][N:17]([C:2]([O:3][C:4]([Cl:7])([Cl:6])[Cl:5])=[O:1])[C@H:18]1[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])[C@H:20]([C:30]([O:32][CH2:33][CH:34]=[CH2:35])=[O:31])[CH2:19]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: C=CCOC(=O)[C@@H]1C[C@@H](NOCc2ccccc2)CN1C(=O)OC(C)(C)C
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=CCOC(=O)[C@@H]1C[C@@H](N(OCc2ccccc2)C(=O)OC(Cl)(Cl)Cl)CN1C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 4 h

Procedure:
Diphosgene (0.1 mL, 0.804 mmol) was added slowly to a solution of 2-allyl 1-tert-butyl (2S,4R)-4-[(benzyloxy)amino]pyrrolidine-1,2-dicarboxylate (261 mg, 0.745 mmol) and triethylamine (0.13 mL, 0.933 mmol) in dichloromethane (4 mL) at 0° C. The reaction mixture was stirred at 0° C. for 4 hours then allowed to stand at room temperature overnight. The reaction mixture was chromatographed on silica gel eluted first with hexane then with 4:1 hexane:ethyl acetate to afford the title compound as a clear gum.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]=1[CH2:11][CH2:12][NH2:13].[C:14](N1C=CN=C1)(N1C=CN=C1)=[O:15]>O1CCCC1>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]2[C:14](=[O:15])[NH:13][CH2:12][CH2:11][C:3]=12
Reactant: Cc1c(CCN)[nH]c2ccccc12
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: Cc1c2n(c3ccccc13)C(=O)NCC2
Temperature: 100 °C
Reaction time: 1 h
Yield: 40.5 %

Procedure:
To a solution of 2-(3-methylindol-2-yl)ethylamine (1.74 g) in tetrahydrofuran (200 ml) at room temperature was added 1,1'-carbonyldiimidazole (1.6 g) in small portions. After one hour of stirring, the reaction mixture was evaporated in vacuo. The residue was dissolved in toluene and the solution was evaporated in vacuo. The oil obtained was heated at 100° C. for 40 minutes and then cooled. Purification of the residue with silica gel column chromatography (chloroform) gave 3,4-dihydro-5-methylpyrimido[1,6-a]indol-1(2H)-one (0.8 g).
Reaction SMILES: C(=O)=[N:2][S:3](Cl)(=[O:5])=[O:4].[CH3:8][O:9][C:10](=[O:24])[C:11]1[CH:16]=[C:15]([CH:17]([CH3:19])[CH3:18])[C:14]([OH:20])=[C:13]([CH:21]([CH3:23])[CH3:22])[CH:12]=1>C1(C)C=CC=CC=1>[CH3:8][O:9][C:10](=[O:24])[C:11]1[CH:12]=[C:13]([CH:21]([CH3:22])[CH3:23])[C:14]([O:20][S:3](=[O:4])(=[O:5])[NH2:2])=[C:15]([CH:17]([CH3:19])[CH3:18])[CH:16]=1
Reactant: O=C=NS(=O)(=O)Cl
Reactant: COC(=O)c1cc(C(C)C)c(O)c(C(C)C)c1
Solvent: Cc1ccccc1
Product: COC(=O)c1cc(C(C)C)c(OS(N)(=O)=O)c(C(C)C)c1
Temperature: 25 °C
Yield: 49.1 %

Procedure:
N-Chlorosulfonyl isocyanate (2.12 mL, 24.3 mmol) was added slowly to a warm solution of 3,5-diisopropyl-4-hydroxy-benzoic acid methyl ester (5.47 g, 23.1 mmol) in 300 mL toluene. The resulting solution was heated to reflux for 6 hours and then cooled to room temperature and concentrated to give a brown oil. Quenched with 200 g ice and extracted with ethyl acetate. The organic solution was dried over magnesium sulfate, filtered, and concentrated to give a tan solid. Chromatography on silica gel (20% ethyl acetate/hexanes) gave 3.58 g of the title compound as an off-white solid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[CH3:15][C:16]1([CH2:21][CH2:22][CH2:23][NH2:24])[O:20][CH2:19][CH2:18][O:17]1.C(N(CC)CC)C>ClCCl>[CH3:15][C:16]1([CH2:21][CH2:22][CH2:23][NH:24][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][C:3]=2[N+:12]([O-:14])=[O:13])[O:20][CH2:19][CH2:18][O:17]1
Reactant: O=[N+]([O-])c1cnc2ccccc2c1Cl
Reactant: CC1(CCCN)OCCO1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(CCCNc2c([N+](=O)[O-])cnc3ccccc23)OCCO1
Yield: 64.3 %

Procedure:
The general method described in Step 1 of Example 1 was used to react 4-chloro-3-nitroquinoline (45.0 g, 216 mmol), 3-(2-methyl-[1,3]dioxolan-2-yl)propylamine (37.0 g, 255 mmol, prepared as described in PCT Publication WO 01/51486) and triethylamine (37.0 g, 366 mmol) in dichloromethane for 15 hours to provide [3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-(3-nitroquinolin-4-yl)amine (44.1 g) as a yellow solid after recrystallization from a toluene/hexane mixture.
Reaction SMILES: [C:1]([C:3]1[CH:21]=[CH:20][C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=2)[C:13](OC)=[O:14])=[O:8])=[CH:5][CH:4]=1)#[N:2].O.[NH2:23][NH2:24]>CCO>[C:1]([C:3]1[CH:21]=[CH:20][C:6]([C:7]([NH:9][C:10]2[CH:19]=[CH:18][CH:17]=[C:12]([C:13]([NH:23][NH2:24])=[O:14])[CH:11]=2)=[O:8])=[CH:5][CH:4]=1)#[N:2]
Reactant: COC(=O)c1cccc(NC(=O)c2ccc(C#N)cc2)c1
Reactant: NN
Solvent: O
Solvent: CCO
Product: N#Cc1ccc(C(=O)Nc2cccc(C(=O)NN)c2)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 68 %

Procedure:
To a suspension of methyl 3-[(4-cyanobenzoyl)amino]benzoate (762 mg, 2.72 mmol) in EtOH (8 mL) was added hydrazine hydrate (1.79 mL). After stirring for 15 h at reflux, the reaction mixture was cooled to rt and a white solid precipitated out. Filtration, washing with EtOH (3 mL) and water (3×3 mL) and drying under vacuo at 60° C. for 2 hrs gave 518 mg of the title compound (68%) as a white solid in 98.8% purity by HPLC (MaxPlot detection between 230 and 400 nm).
Reaction SMILES: C=CC(CCC=C(C)C)(C)O.[OH:12][CH2:13]/[CH:14]=[C:15](/[CH3:22])\[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20].CC(=CCC/C(=C/CO)/C)C>>[CH3:20][C:19](=[CH:18][CH2:17][CH2:16][CH:15]([CH2:14][CH2:13][OH:12])[CH3:22])[CH3:21]
Reactant: CC(C)=CCC/C(C)=C\CO
Agent: C=CC(C)(O)CCC=C(C)C
Agent: CC(C)=CCC/C(C)=C/CO
Product: CC(C)=CCCC(C)CCO

Procedure:
A portion of the reaction was steam distilled to provide a crude product having a ratio of linalool to nerol plus geraniol to cis- and trans-isogeraniols of 62 to 25 to 13, respectively. The isogeraniols, while not known to be useful in perfumery, can be (like geraniol) hydrogenated to yield citronellol, a valuable perfumery material.
Reaction SMILES: Cl[P:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1COCC1.CC(C)([O-])C.[K+].Cl[CH2:27][C:28]1[N:33]=[C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)[CH:31]=[CH:30][CH:29]=1>CCOCC.O>[C:3]1([P:2]([CH2:27][C:28]2[N:33]=[C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=3)[CH:31]=[CH:30][CH:29]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: ClCc1cccc(-c2ccccn2)n1
Reactant: ClP(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOCC
Product: c1ccc(P(Cc2cccc(-c3ccccn3)n2)c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 61 %

Procedure:
Synthesis of the Ligand BPy-(Ph)PNN (10) An oven-dried 250 mL three-necked round bottom flask equipped with an argon inlet, a stirring bar, dropping funnel and one rubber septum was cooled under a stream of argon. The flask was then charged with chlorodiphenylphosphine (1.08 g, 6 mmol) in 30 mL dry ether. The solution was cooled to 0° C. and a THF solution (5 mL) of potassium tert-butoxide (74 mg, 6.6 mmol) was added dropwise via syringe during 10 min. The resulting brown coloured mixture was stirred for 1 hr at 0° C. and then a solution of 6-chloromethyl-2,2′-bipyridine (1.02 g, 5 mmol) in 20 mL dry ether was added dropwise (˜15 min) to it. The stirring was continued for a further 1 hr at the same temperature and the mixture was allowed to slowly warm up to room temperature and stirred overnight. To this reaction mixture was added 20 mL of degassed water and the ether phase was separated under N2 atmosphere. The aqueous phase was extracted with ether (2×20 mL). The combined ether solutions were dried over anhydrous Na2SO4, filtered under N2 pressure, and the solvent was removed under vacuum to get brownish-white solid. This was purified by column chromatography in the nitrogen glove box (basic alumina; hexane:ether (10:1) as eluent) to yield 1.08 g (61%) of 6-di-phenyphosphinomethyl-2,2′-bipyridine (BPy-(Ph)PNN) as a white crystalline solid.