Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([OH:26])=[C:21]([CH:25]=1)[C:22]([NH2:24])=[O:23]>CN(C)C1C=CN=CC=1.ClC1C=CC=CC=1Cl>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([O:26][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[C:21]([CH:25]=1)[C:22]([NH2:24])=[O:23]
Reactant: COc1cc2nccc(Cl)c2cc1OC
Reactant: NC(=O)c1cc(Cl)ccc1O
Agent: CN(C)c1ccncc1
Solvent: Clc1ccccc1Cl
Product: COc1cc2nccc(Oc3ccc(Cl)cc3C(N)=O)c2cc1OC
Temperature: 120 °C
Reaction time: 8 h
Yield: 165.2 %

Procedure:
4-Chloro-6,7-dimethoxyquinoline (100 mg), 5-chloro-2-hydroxybenzamide (343 mg), and 4-dimethylaminopyridine (244 mg) were suspended in o-dichlorobenzene (1 ml), and the suspension was stirred at 120° C. overnight. The reaction solution was cooled to room temperature, and the solvent was removed therefrom by distillation under the reduced pressure. The residue was purified by column chromatography using acetone-hexane to give the title compound (265 mg, yield 100%).
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][C:6]1[N:10]=[N:9][N:8]([CH:11]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][C:17]([O:23][CH2:24][CH2:25][O:26][CH3:27])=[CH:16]3)[CH3:12])[C:7]=1[C:28]([NH:30][C:31]1[S:35][N:34]=[C:33]([CH3:36])[CH:32]=1)=[O:29])C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClC(Cl)C.ClCCl>[CH3:27][O:26][CH2:25][CH2:24][O:23][C:17]1[CH:18]=[N:19][C:20]2[C:15]([CH:16]=1)=[CH:14][C:13]([C@@H:11]([N:8]1[C:7]3[C:28](=[O:29])[N:30]([C:31]4[S:35][N:34]=[C:33]([CH3:36])[CH:32]=4)[CH:4]=[CH:5][C:6]=3[N:10]=[N:9]1)[CH3:12])=[CH:22][CH:21]=2
Reactant: CCOC(Cc1nnn(C(C)c2ccc3ncc(OCCOC)cc3c2)c1C(=O)Nc1cc(C)ns1)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Solvent: CC(Cl)Cl
Product: COCCOc1cnc2ccc([C@H](C)n3nnc4ccn(-c5cc(C)ns5)c(=O)c43)cc2c1
Temperature: 100 °C

Procedure:
5-(2,2-diethoxyethyl)-3-(1-(3-(2-methoxyethoxy)quinolin-6-yl)ethyl)-N-(3-methylisothiazol-5-yl)-3H-1,2,3-triazole-4-carboxamide (0.296 g, 0.53 mmol) was dissolved in dichloroethane (5 mL) and to the solution was added p-toluenesulfonic acid monohydrate (0.11 g, 0.59 mmol). The reaction mixture was heated at 100° C. overnight. The reaction mixture was diluted with dichloromethane then washed with sat. aq. sodium bicarbonate and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The enantiomers were separated via preparative SFC (ChiralPak® AD-H, 20×250 mm, 40:60:0.2 IPA:CO2:DEA, 80 mL/min; tr 1.38 min) to yield (S)-3-(1-(3-(2-methoxyethoxy)quinolin-6-yl)ethyl)-5-(3-methylisothiazol-5-yl)-3H-[1,2,3]triazolo[4,5-c]pyridin-4(5H)-one as a pale yellow solid. On the basis of previous crystallographic data and potency recorded for related compounds in the same program, the absolute stereochemistry was assigned as the S enantiomer. MS m/z=463.2 [M+1]+. Calc'd 462.5 for C23H22N6O3S. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.15 (d, 3 H) 2.39-2.44 (m, 3 H) 3.30-3.32 (m, 3 H) 3.71 (dd, 2 H) 4.23 (dd, 2 H) 6.89 (q, 1 H) 7.33 (d, 1 H) 7.64 (dd, 1 H) 7.74-7.82 (m, 3 H) 7.94 (d, 1 H) 8.34 (d, 1 H) 8.61 (d, 1 H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6](Cl)[C:5]([Cl:12])=[CH:4][N:3]=1.[N:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[Cl:12][C:5]1[C:6]([N:23]2[CH2:24][CH2:25][N:20]([CH2:19][C:16]3[CH:15]=[CH:14][N:13]=[CH:18][CH:17]=3)[CH2:21][CH2:22]2)=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([NH2:1])=[N:3][CH:4]=1
Reactant: c1cc(CN2CCNCC2)ccn1
Reactant: Nc1ncc(Cl)c(Cl)c1[N+](=O)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Nc1ncc(Cl)c(N2CCN(Cc3ccncc3)CC2)c1[N+](=O)[O-]
Temperature: 45 °C

Procedure:
To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.052 g, 0.25 mmol) and isopropanol (4.5 ml) was added 1-[(4-pyridyl)-methyl]-piperazine (0.049 g, 0.28 mmol) followed by diisopropylethylamine (0.05 ml, 0.28 mmol). The reaction mixture was heated at 45° C. for 24 h, then allowed to cool to room temperature, and diluted with isopropanol (3 ml). The precipitate was collected by filtration and washed with isopropanol and diethyl ether. The title compound was thus obtained as yellow solid (0.035 g). The filtrate was concentrated in vacuo, and purification of the residue on a isolute silica column using 0 to 5% methanol in ethyl acetate/dichloromethane (v/v; 1:1) as eluant gave an additional 0.036 g of the product (total yield: 81%); 1H-NMR (500 MHz, DMSO-d6) 3.09 (br s, 4H, piperazine N(CH2)2), 3.57 (s, 2H, NCH2), 6.96 (s, 2H, NH2), 7.34 (d, J=5.81 Hz, 2H), and 8.51 (d, J=5.88 Hz, 2H) (pyrid-4-yl protons), 8.06 (s, 1H, 6-H);
Reaction SMILES: [CH2:1]([N:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[C:9]([OH:11])=O)[CH:2]=[CH2:3].[CH2:12]([C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17])[CH3:13].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.S([O-])(O)(=O)=O.[K+]>ClCCl>[CH2:1]([N:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[C:9]([NH:17][C:16]1[CH:18]=[CH:19][CH:20]=[C:14]([CH2:12][CH3:13])[CH:15]=1)=[O:11])[CH:2]=[CH2:3]
Reactant: C=CCn1cccc1C(=O)O
Reactant: CCc1cccc(N)c1
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCn1cccc1C(=O)Nc1cccc(CC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 50.3 %

Procedure:
A mixture of 1-allyl-1H-pyrrole-2-caboxylic acid (270 mg, 1.79 mmol), m-ethylaniline (0.43 g, 2.48 mmol), BOP-Cl (500 mg, 1.96 mmol) and triethylamine (210 mg, 2.08 mmol) in dichloromethane (3 ml) was stirred for 2 hours at room temperature. To the reaction mixture was added an aqueous 5% potassium hydrogensulfate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution, and dried over magnesium sulfate. The solvent was removed and the residue was purified with silica gel chromatography (hexane:ethyl acetate=5:1→3:1) to give the subject compound (229 mg, 50%).
Reaction SMILES: C[O:2][CH:3]=[C:4]1[CH2:11][CH:10]2[S:12][CH:6]([CH2:7][CH2:8][CH2:9]2)[CH2:5]1.O.Cl.C(OCC)(=O)C>C1COCC1.C1CCN2C(=NCCC2)CC1>[CH:10]12[S:12][CH:6]([CH2:7][CH2:8][CH2:9]1)[CH2:5][CH:4]([CH:3]=[O:2])[CH2:11]2
Reactant: COC=C1CC2CCCC(C1)S2
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: O=CC1CC2CCCC(C1)S2
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.9 %

Procedure:
To a solution of 3-Methoxymethylene-9-thia-bicyclo[3.3.1]nonane (2.50 g, 13.56 mmol) in THF (35 ml) were added water (7 ml) and a 4M solution of HCl (6.78 ml, 27.10 mmol) and the reaction mixture was stirred for 16 hrs at 55° C. The reaction mixture was quenched with a saturated aqueous solution of NaHCO3, ethyl acetate was added and extracted with ethyl acetate. The organic phases were combined, washed with brine, dried using Na2SO4, filtered and concentrated in vacuo. The remaining oil was dissolved in THF/MeOH 1/1 (60 ml), DBU (0.146 g, 0.14 ml, 0.957 mmol) was added and the solution was stirred at RT for 1 hr. Ethyl acetate (150 ml), the reaction mixture was neutralized using a solution of 0.5 M HCl and extracted with ethyl acetate. The combined organic phases were washed with brine, dried using Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluting with a gradient of hexanes:ethyl acetate 100:0 to 75:25) yielding the title intermediate (2.21 g, 12.33 mmol, 64%) as a colourless oil.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]1([N:16]2[C:20](=[O:21])[CH:19]=[C:18]([NH2:22])[N:17]2[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[N+](C1C=CC=CC=1)([O-])=O.[Cl-].[Al+3].[Cl-].[Cl-]>C(#N)C.O>[C:10]1([N:16]2[C:20](=[O:21])[CH:19]=[C:18]([NH:22][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[N:17]2[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CCOC(=O)n1c(N)cc(=O)n1-c1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC#N
Solvent: O=[N+]([O-])c1ccccc1
Solvent: O
Product: CCOC(=O)n1c(NC(=O)c2ccccc2)cc(=O)n1-c1ccccc1

Procedure:
15.4 g (0.11 mole) of benzoyl chloride are added at room temperature to a solution of 24.7 g (0.1 mole) of 1-phenyl-2-ethoxycarbonyl-3-amino-3-pyrazolin-5-one (compound 2),3 ml of nitrobenzene, and 26.7 g (0.2 mole) of anhydrous aluminium chloride in 100 ml of acetonitrile. The solution is refluxed for 3 h and then poured out into water. The precipitate is filtered off, rinsed with water, dried, and recrystallized from acetonitrile.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]2[CH2:14][CH2:13][N:12](CC3C=CC=CC=3)[CH2:11][CH2:10]2)=[CH:4][N:3]=1>C(O)C.C(O)(=O)C.[Pd]>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][N:3]=1
Reactant: Nc1ncc(C2CCN(Cc3ccccc3)CC2)c(N)n1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: Nc1ncc(C2CCNCC2)c(N)n1

Procedure:
A solution of 26 g of 2,4-diamino-5-(1-benzyl-4-piperidinyl)pyrimidine in 700 ml of ethanol and 20 ml of acetic acid was hydrogenated over 5 g of Pd/C 10% at room temperature and normal pressure up to the standstill of the hydrogen uptake, whereupon it was filtered off from catalyst. The filtrate was concentrated and the crystalline residue was dissolved in 100 ml of water. Chromatography on Dowex 1 (×10 200-400 mesh) (a cation exchange resin) gave 2,4-diamino-5-(4-piperidyl)-pyrimidine of melting point 230°-231° C. (dec.) (from water).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5]Cl.[N-:11]=[N+:12]=[N-:13].[Na+].O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:5][N:11]=[N+:12]=[N-:13])[CH:7]=[CH:8][C:9]=1[Cl:10]
Reactant: [N-]=[N+]=[N-]
Reactant: ClCc1ccc(Cl)c(Cl)c1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: [N-]=[N+]=NCc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 138.6 %

Procedure:
A mixture of 3,4-dichlorobenzyl chloride (10 g, 0.05 mol), sodium azide (5 g, 0.08 mol) in DMSO (100 mL) was stirred at room temperature overnight. The mixture was poured into water (150 mL). The water layer was extracted with EtOAc (100 ml×3). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by distillation to give the title compound as an oil (14 g, quantitative yield). LC/MS: m/z 203 (M+H)+. Rt: 2.26 min.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][C:9]#[N:10])=[C:6]([N:11]([CH3:13])[CH3:12])[N:5]=[C:4]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[CH:33]=[CH:32][C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=3)=[O:23])=[CH:17][CH:16]=2)[N:3]=1.[N-:34]=[N+:35]=[N-:36].[Na+].CC(O)C>[Br-].[Br-].[Zn+2].O.CCOC(C)=O.O1CCOCC1>[Cl:1][C:2]1[C:7]([CH2:8][C:9]2[NH:36][N:35]=[N:34][N:10]=2)=[C:6]([N:11]([CH3:13])[CH3:12])[N:5]=[C:4]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[CH:33]=[CH:32][C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=3)=[O:23])=[CH:17][CH:16]=2)[N:3]=1
Reactant: [N-]=[N+]=[N-]
Reactant: CN(C)c1nc(Cc2ccc(NC(=O)c3ccc4ccccc4c3)cc2)nc(Cl)c1CC#N
Agent: [Br-]
Agent: [Na+]
Agent: [Zn+2]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Solvent: O
Product: CN(C)c1nc(Cc2ccc(NC(=O)c3ccc4ccccc4c3)cc2)nc(Cl)c1Cc1nnn[nH]1
Temperature: 25 °C
Reaction time: 2 h
Yield: 31.2 %

Procedure:
A solution containing N-(4-{[4-chloro-5-(cyanomethyl)-6-(dimethylamino)pyrimidin-2-yl]methyl}phenyl)-2-naphthamide (0.279 g, 0.61 mmol), sodium azide (0.159 g, 2.44 mmol), zinc dibromide (0.345 g, 1.55 mmol), 2-propanol (2.7 mL), water (4 mL), and 1,4-dioxane (5 mL) was heated at reflux for 24 hours. After cooling to room temperature, EtOAc (4 mL) was added and stirring was continued for 2 hours. The resulting mixture was poured into water and the precipitate thus formed was collected by suction, rinsed with water and MeOH, and dried in vacuo to give N-(4-{[4-chloro-6-(dimethylamino)-5-(1H-tetrazol-5-ylmethyl)pyrimidin-2-yl]methyl}-phenyl)-2-naphthamide as a light beige solid (0.095 g, 31%).
Reaction SMILES: [Li+:1].[CH3:2][CH:3]([N-:5][CH:6]([CH3:8])[CH3:7])[CH3:4].[SH:9][C:10]1[S:11][CH:12]=[CH:13][N:14]=1.[CH3:15][C:16](=[O:19])[CH2:17][CH3:18]>C1COCC1.CCOCC>[Li+:1].[CH3:2][CH:3]([N-:5][CH:6]([CH3:8])[CH3:7])[CH3:4].[SH:9][C:10]1[S:11][C:12]([C:16]([OH:19])([CH2:17][CH3:18])[CH3:15])=[CH:13][N:14]=1
Reactant: Sc1nccs1
Reactant: CCC(C)=O
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCC(C)(O)c1cnc(S)s1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
A solution of LDA (59 mmol) in THF was prepared at −10° C. and cooled to −78° C. To the LDA was added a solution of 2-mercaptothiazole (3.00 g, 25.6 mmol) in 5 mL of THF. After 15-20 min of stirring a solution of 2-butanone (2.23 mL, 38.4 mmol) was added, and the reaction mixture was stirred at −78° C. for 2 h. The reaction mixture was diluted with ether and washed successively with aq. 2N HCl, H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was washed with Et2O to give the title compound.
Reaction SMILES: [CH2:1]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]([OH:26])=[O:25])=[CH:19][CH:18]=1)[CH2:2][CH2:3][CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].CN(C)P(N(C)C)(N(C)C)=O.[OH-].[Na+].Cl[CH2:41][CH:42]([OH:45])[CH2:43][OH:44]>O.CCOCC>[CH2:1]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26][CH2:41][CH:42]([OH:45])[CH2:43][OH:44])=[O:25])=[CH:19][CH:18]=1)[CH2:2][CH2:3][CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: OCC(O)CCl
Reactant: CCCCCCCCCCC=CCCCNc1ccc(CC(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOCC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCCCCCCCCCC=CCCCNc1ccc(CC(=O)OCC(O)CO)cc1

Procedure:
A solution of 7.35 g. of 4-(4-pentadecenyl)aminophenylacetic acid in 50 ml. of hexamethylphosphoramide is treated with 4.80 g. of 25% aqueous sodium hydroxide followed by 11.0 g. of 3-chloro-1,2-propanediol and then is heated at 140° C. for 6 hours. The mixture is diluted with water and ether and filtered to yield a white solid. Recrystallization from acetonitrile and then from carbon tetrachloride affords the product as a white solid.
Reaction SMILES: C(OC(OCC(C)(C)C)N(C)C)C(C)(C)C.[Cl:17][C:18]1[CH:19]=[N:20][C:21](=[O:24])[NH:22][CH:23]=1.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31]O)[CH:26]=1>CN(C)C=O>[Cl:17][C:18]1[CH:19]=[N:20][C:21](=[O:24])[N:22]([CH2:31][C:27]2[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=2)[CH:23]=1
Reactant: O=c1ncc(Cl)c[nH]1
Reactant: OCc1cccnc1
Agent: CN(C)C(OCC(C)(C)C)OCC(C)(C)C
Solvent: CN(C)C=O
Product: O=c1ncc(Cl)cn1Cc1cccnc1
Temperature: 90 °C

Procedure:
N,N-Dimethylformamide dineopentyl acetal (1.8 ml) was added to a stirred suspension of 5-chloropyrimidin-2-one (522 mg) and 3-pyridylcarbinol (0.55 ml) in dry N,N-dimethylformamide (10 ml) under nitrogen and the mixture was then heated at 90° C. After 1 h the reaction mixture was evaporated to a brown solid which was subjected to column chromatography on silica developing one eluting with chloroform-ethanol, 14:1. This gave a pale yellow solid which was crystallised from acetone to give off white needles of the title pyrimidinone (387 mg), m.p. 191°-193° C., λmax (EtOH) 229.5 nm (ε 8,930), 334 nm (ε 2,530).
Reaction SMILES: [CH3:1][C:2]([CH3:16])=[CH:3][CH2:4][CH2:5]/[C:6](/[CH3:15])=[CH:7]/[CH2:8][CH2:9]/[C:10](/[CH3:14])=[CH:11]/[CH:12]=[O:13].C(N(CC)CC)C.[P:24]([O-:29])([O:27][CH3:28])[O:25][CH3:26]>C(#N)C>[OH:13][CH:12]([P:24](=[O:29])([O:27][CH3:28])[O:25][CH3:26])/[CH:11]=[C:10](\[CH3:14])/[CH2:9][CH2:8]/[CH:7]=[C:6](\[CH3:15])/[CH2:5][CH2:4][CH:3]=[C:2]([CH3:16])[CH3:1]
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/C=O
Reactant: COP([O-])OC
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COP(=O)(OC)C(O)/C=C(\C)CC/C=C(\C)CCC=C(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a stirred solution of farnesal (245 mg, 1.11 mmol) in acetonitrile (1.1 ml) under argon at room temperature (r.t), was added triethylamine (0.31 ml, 2.22 mmol) and dimethyl phosphite (0.153 ml, 1.67 mmol) and the resulting mixture stirred at r.t. for 24 hr. The reaction mixture was concentrated in vacuo, the resulting residue was chromatographed over silica gel eluted with ethyl acetate to afford the title compound as a colorless oil: NMR (CDCl3) δ 1.60 (6H, s), 1.68 (3H, s), 1.71 (3H, d, J=3.1 Hz), 1.80-2.30 (9H, m), 3.80 (6H, m), 4.69 (1H, dt, J=9 and 5.4 Hz), 5.00-5.20 (2H, m), 5.34 (1H, m).
Reaction SMILES: C(OC(=O)[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:38])[CH2:18][N:19]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]2[C:28]2[C:32]([NH:33][CH2:34][CH2:35][C:36]#[N:37])=[N:31][O:30][N:29]=2)=[CH:13][CH:12]=1)C1C=CC=CC=1.C(OCC)(=O)C.CO>C(OCC)(=O)C.CO.[Pd]>[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:17](=[O:38])[CH2:18][N:19]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]2[C:28]2[C:32]([NH:33][CH2:34][CH2:35][C:36]#[N:37])=[N:31][O:30][N:29]=2)=[CH:15][CH:16]=1
Reactant: N#CCCNc1nonc1-c1nc2ccccc2n1CC(=O)c1ccc(NC(=O)OCc2ccccc2)cc1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: N#CCCNc1nonc1-c1nc2ccccc2n1CC(=O)c1ccc(N)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 73.5 %

Procedure:
To a suspension of 6.4 g of [4-(2-{2-[4-(2-cyano-ethylamino)-furazan-3-yl]-benzoimidazol-1-yl}-acetyl)-phenyl]-carbamic acid benzyl ester (12.3 mmol, 1 eq) in a mixture of 700 ml of ethyl acetate and 500 ml of methanol are added 1.3 g of 10% palladium on carbon. The reaction mixture is stirred for 3 h under hydrogen atmosphere (1 atm) at room temperature. Then it is filtered through celite and concentrated under reduced pressure to give the crude product as a light yellow solid, which is suspended in 60 ml of a 7/5 ethyl acetate/methanol mixture. Filtration provides 3.5 g of the desired product as off-white solid. The filtrate is concentrated and the residue is treated as above with 5 ml of the 7/5 ethyl acetate/methanol mixture. Filtration gives 0.45 g of a second crop of the product.
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.CC(C)([O-])C.[Na+].C1(C(C2C=CC=CC=2)=C(P(C2CCCCC2)C2CCCCC2)C)C=CC=CC=1.[Cl-].[NH4+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:3][CH:4]=1)#[N:7]
Reactant: N#Cc1ccc(Cl)cc1
Reactant: C1COCCN1
Agent: [Pd+2]
Agent: CC(=C(c1ccccc1)c1ccccc1)P(C1CCCCC1)C1CCCCC1
Agent: CC(=O)[O-]
Solvent: Cc1ccccc1
Product: N#Cc1ccc(N2CCOCC2)cc1
Temperature: 100 °C
Reaction time: 14 h
Yield: 80.8 %

Procedure:
Into a reactor were introduced 0.275 g (2.00 mmol) of 4-chlorobenzonitrile and 4 mL of toluene under a nitrogen atmosphere. The nitrile was dissolved in the solvent. To this solution were added 0.192 g (2.2 mmol) of morpholine, 0.231 g (2.4 mmol) of sodium t-butoxide, 4.5 mg (1 mol % based on the amine) of palladium acetate, and 15.6 mg (2 mmol % based on the amine) of the 1,1-diphenyl-2(dicyclohexylphosphino)propene obtained in Example 2. The resultant reaction mixture was stirred at 100° C. for 14 hours and then cooled. Saturated aqueous ammonium chloride solution was added thereto, and this mixture was extracted with toluene. The extract was dried with anhydrous magnesium sulfate. Thereafter, the solvent was removed under reduced pressure. The concentrate was purified by column chromatography to obtain 0.304 g (81%) of N-(4-cyanophenyl)morpholine as light-yellow crystals. The results obtained are shown in Table 20.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH2:18][OH:19])([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:5]2[C:10]([CH2:11][CH:12]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[CH3:1][O:2][C:3]1[C:4]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])([CH:18]=[O:19])[C:5]2[C:10]([CH2:11][CH:12]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: COC1=CCc2ccccc2C1(CO)CCC(C)C
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: COC1=CCc2ccccc2C1(C=O)CCC(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 53.9 %

Procedure:
To a solution of Example 179A (0.6 g, 2.3 mmol) in dichloromethane (15 mL) was added Dess-Martin periodanate (1.5 g, 3.5 mmol). The solution was stirred at room temperature for 18 h and then concentrated in vacuo. Column chromatography on silica (10%-20%-30% dichloromethane/hexane) afforded product as a light yellow oil (0.32 g, 53%). 1H NMR (300 MHz, CDCl3) δ ppm 0.63 (m, 1 H), 0.76 (dd, J=12.13, 6.62 Hz, 6 H), 0.92 (m, 1 H), 1.41 (m, 1 H), 1.93 (m, 1 H), 2.18 (m, 1 H), 3.59 (m, 5 H), 5.19 (t, J=3.68 Hz, 1 H), 7.01 (m, 1 H), 7.21 (m, 3 H), 9.40 (s, 1 H).
Reaction SMILES: [CH:1]1([NH2:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[Br:11]C1C=C2C(CCC2=O)=CC=1.[BH3-]C#N.[Na+]>>[Br:11][C:7]1[CH:8]=[C:9]2[C:4]([CH2:3][CH2:2][CH:1]2[NH2:10])=[CH:5][CH:6]=1
Reactant: O=C1CCc2ccc(Br)cc21
Reactant: NC1CCc2ccccc21
Agent: [BH3-]C#N
Agent: [Na+]
Product: NC1CCc2ccc(Br)cc21

Procedure:
The title indanamine was generated from 6-bromo-1-indanone (2.00 g, 9.50 mmol), NaBH3CN (4.20 g, 66.84 mmol) and NH4OAc (22.00 g, 0.29 mol) according to the protocols as outlined in general procedure C. Spectroscopic data: 1H NMR (300 MHz, CDCl3) δ 1.59-1.73 (m, 3H), 2.44-2.56 (m, 1H), 2.70-2.82 (m, 1H), 2.84-2.98 (m, 1H), 4.29-4.40 (m, 1H), 6.98-7.18 (m, 1H), 7.26-7.38 (m, 1H), 7.4 (s, 1H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][C@H:9]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([S:27]([CH3:30])(=[O:29])=[O:28])[N:3]=1.[CH2:31]1[C:35]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:34][CH:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[N:32]1[C:46]([O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:47].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C@@H:9]([O:8][C:6]2[N:5]=[C:4]([S:27]([CH3:30])(=[O:29])=[O:28])[N:3]=[C:2]([N:38]3[CH2:37][CH2:36][C:35]4([CH2:31][N:32]([C:46]([O:48][CH2:49][C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)=[O:47])[C@H:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:34]4)[CH2:40][CH2:39]3)[CH:7]=2)[C:10]([F:12])([F:13])[F:11])=[C:15]([N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[CH:16]=1
Reactant: Cc1ccn(-c2cc(Cl)ccc2[C@@H](Oc2cc(Cl)nc(S(C)(=O)=O)n2)C(F)(F)F)n1
Reactant: CCOC(=O)C1CC2(CCNCC2)CN1C(=O)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: CCOC(=O)[C@@H]1CC2(CCN(c3cc(O[C@H](c4ccc(Cl)cc4-n4ccc(C)n4)C(F)(F)F)nc(S(C)(=O)=O)n3)CC2)CN1C(=O)OCc1ccccc1
Temperature: 100 °C
Yield: 31.8 %

Procedure:
To a solution of 4-chloro-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-methylsulfonylpyrimidine (2.49 g, 5.17 mmol) in dioxane (100 mL) was added 2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (1.8 g, 5.2 mmol), Cs2CO3 (5.06 g, 15.5 mmol), and the reaction mixture was heated to 100° C. for 1.5 h. The reaction mixture was cooled to RT, quenched with brine, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification on a 120 g Isco RediSep silica cartridge (EtOAc:heptane) provided (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(methylsulfonyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid (1.3 g) in addition to (S)-2-benzyl 3-ethyl 8-(4-chloro-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate.