Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]([O:23][C:24]([F:43])([F:42])[C:25]([F:41])([F:40])[O:26][C:27]([F:39])([F:38])[C:28]([F:37])([F:36])[C:29]([F:35])([F:34])[C:30]([F:33])([F:32])[F:31])([F:22])[F:21])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[CH2:44]([O:46][CH2:47][CH2:48]Br)[CH3:45]>>[CH2:44]([O:46][CH2:47][CH2:48][O:1][C:2]1[CH:7]=[N:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]([O:23][C:24]([F:43])([F:42])[C:25]([F:40])([F:41])[O:26][C:27]([F:38])([F:39])[C:28]([F:36])([F:37])[C:29]([F:34])([F:35])[C:30]([F:31])([F:32])[F:33])([F:22])[F:21])=[CH:12][CH:13]=2)=[N:4][CH:3]=1)[CH3:45]
Reactant: Oc1cnc(-c2ccc(OCCCOCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)nc1
Reactant: CCOCCBr
Product: CCOCCOc1cnc(-c2ccc(OCCCOCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)nc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 5-hydroxy-2-[4-(3-(2-(2-(nonafluorobutoxy)tetrafluoroethoxy)-2,2-difluoroethoxy)propoxy)phenyl]pyrimidine (1.0 g, 1.51 mmol,) and 2-bromoethyl ethyl ether (0.58 g, 3.79 mmol). The resulting crude product was isolated and further purified essentially as described in Example 3, eluting with 30 volume percent ethyl acetate/hexane, to yield 0.76 g of purified product.
Reaction SMILES: [N:1]1([C:7]2[N:12]=[C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:10]=[C:9]([C:19]3[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=3)[N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[N:34]=[C:35]=[O:36]>>[F:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[NH:34][C:35]([NH:23][C:22]1[CH:24]=[CH:25][C:19]([C:9]2[N:8]=[C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[N:12]=[C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:10]=2)=[CH:20][CH:21]=1)=[O:36]
Reactant: O=C=Nc1ccc(F)cc1F
Reactant: Nc1ccc(-c2nc(N3CCOCC3)nc(N3CCOCC3)n2)cc1
Product: O=C(Nc1ccc(-c2nc(N3CCOCC3)nc(N3CCOCC3)n2)cc1)Nc1ccc(F)cc1F

Procedure:
Starting from 4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)aniline (0.105 g 0.30 mmoles) and 2,4-difluorophenyl isocyanate (71 mg, 0.45 mmoles) the title compound was isolated as a white solid. Yield; 40 mg (27%); (M+H)=498.6
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([CH3:22])[N:17]([CH3:23])[C:16]2=[O:24])=[CH:10][C:3]=1[C:4]([O:6]C(C)C)=[O:5].S(=O)(=O)(O)O>C(Cl)Cl>[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([CH3:22])[N:17]([CH3:23])[C:16]2=[O:24])=[CH:10][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: Cc1cc(=O)n(-c2cc(C(=O)OC(C)C)c(Cl)cc2F)c(=O)n1C
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: Cc1cc(=O)n(-c2cc(C(=O)O)c(Cl)cc2F)c(=O)n1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 35 g of isopropyl 2-chloro-5-[3,6-dihydro-2,6-dioxo-3,4-dimethyl-1(2H)-pyrimidinyl]-4-fluorobenzoate, 165 ml of concentrated sulphuric acid and 165 ml of methylene chloride is stirred well at room temperature for 30 minutes. Subsequently, the reaction mixture is poured cautiously onto 500 g of ice. The aqueous mixture is extracted twice with 250 ml of ethyl acetate each time and the organic phase is extracted three times with 200 ml of saturated sodium bicarbonate solution each time. The aqueous sodium bicarbonate solutions are combined and acidified with concentrated sulphuric acid. The separated product is extracted twice with 600 ml of ethyl acetate each time and the organic phases are washed twice with 200 ml of water each time, dried over anhydrous magnesium sulphate and concentrated. In this manner there is obtained 2-chloro-5-[3,6-dihydro-2,6-dioxo-3,4-dimethyl-1(2H)-pyrimidinyl]-4-fluorobenzoic acid which can be purified further by digestion in ethanol. M.p. 236°-239° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[CH2:5][NH:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH2:17][OH:18])[CH:13]=2)[N:8]=1.[C:23]1(O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[CH2:5][NH:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH2:17][O:18][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:13]=2)[N:8]=1
Reactant: Oc1ccccc1
Reactant: COc1ccccc1CNc1ccc2cc(CO)ccc2n1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccccc1CNc1ccc2cc(COc3ccccc3)ccc2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
[2-(2-Methoxy-benzylamino)-quinolin-6-yl]-methanol (200 mg, 0.680 mmol) was dissolved in 13 mL tetrahydrofurane. Phenol (70 mg, 0.745 mmol) and triphenylphosphine (200 mg, 0.763 mmol) were added at room temperature. Diisopropyl azodicarboxylate (159 mg, 0.787 mmol) was slowly added at 0° C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched by addition of 50 mL 2N sodium carbonate. The mixture was extracted three times with dichloromethane (50 mL each). The organic phases ware pooled, dried with sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100:0->50:50 gradient). The title compound was obtained as an off-white solid (105 mg, 41%), MS: m/e=371.4 (M+H+).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[C:7]([N+:9]([O-])=O)[CH:6]=[C:5]([Cl:12])[C:4]=1[N:13]=[CH:14][N:15]([CH3:17])[CH3:16]>>[NH2:9][C:7]1[CH:6]=[C:5]([Cl:12])[C:4]([N:13]=[CH:14][N:15]([CH3:16])[CH3:17])=[C:3]([Cl:2])[CH:8]=1
Reactant: CN(C)C=Nc1c(Cl)cc([N+](=O)[O-])cc1Cl
Agent: Cl
Product: CN(C)C=Nc1c(Cl)cc(N)cc1Cl
Temperature: 10 °C
Reaction time: 18 h

Procedure:
A 540 g. amount of stannous chloride is dissolved in 450 ml. of concentrated hydrochloric acid with stirring. The solution is cooled to 10° C. in an ice bath and 155 g. of N'-(2,6-dichloro-4-nitrophenyl)-N,N-dimethylformamidine (prepared as described above) is added portionwise, with stirring, at a rate to maintain the reaction temperature at 75° C. The reaction mixture is allowed to stand at room temperature for 18 hours, then is filtered. The filter cake is suspended in 200 ml. of ice water and concentrated sodium hydroxide is added until the reaction mixture is alkaline. The reaction mixture is filtered and the insolubles are collected and extracted with chloroform. The chloroform extracts are evaporated in vacuo to yield 102 g. of the product of the Example as pale yellow crystals, m.p. 121°-126° C.
Reaction SMILES: [Si]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[CH:36]([O:40][Si](C(C)(C)C)(C)C)[CH2:35][CH2:34]3)=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[CH:18][CH:17]=2)[CH:14]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[CH:36]([OH:40])[CH2:35][CH2:34]3)=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[CH:18][CH:17]=2)[CH:14]=1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(-c2ccc3c(c2)CCC3O[Si](C)(C)C(C)(C)C)c(Nc2ccc(OCCN3CCCCC3)cc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Product: Oc1ccc(-c2ccc3c(c2)CCC3O)c(Nc2ccc(OCCN3CCCCC3)cc2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 79 %

Procedure:
To a solution of {5-(tert-butyldimethylsilyloxy)-2-[1-(tert-butyldimethylsilyloxy)indan-5-yl]phenyl}[4-(2-piperidin-1-ylethoxy)phenyl]amine (590 mg) in tetrahydrofuran (8 ml) was added tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran) (3 ml), and the solution was stirred for 3 hours at room temperature. A saturated aqueous solution of ammonium chloride was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (ethyl acetate-methanol system) to provide the title compound (308 mg).
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH:7]=[O:8])=[C:5]([CH3:9])[O:4][N:3]=1.[BH4-].[Na+].O>CO>[CH3:1][C:2]1[C:6]([CH2:7][OH:8])=[C:5]([CH3:9])[O:4][N:3]=1
Reactant: Cc1noc(C)c1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: Cc1noc(C)c1CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.1 %

Procedure:
To a 0° C. solution of 3,5-dimethyl-1,2-oxazole-4-carbaldehyde (1.0 g, 8.0 mmol) in anhydrous methanol (60 mL) was added sodium borohydride (450 mg, 12.0 mmol). The reaction mixture was stirred at room temperature overnight. Water (50 mL) was added and methanol was evaporated. The resultant mixture was extracted with EtOAc (1×50 mL) and CH2Cl2 (3×50 mL). The organic extracts were combined, dried over MgSO4, filtered, evaporated, and dried in vacuo, affording (3,5-dimethyl-1,2-oxazol-4-yl)methanol (805 mg, 79% yield). The product was used without further purification.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.O[CH:13]1[S:18][C:17]2=[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:20](=[O:27])[N:21]([CH2:24][CH2:25][CH3:26])[C:22](=[O:23])[N:16]2[CH2:15][CH2:14]1>C1(C)C=CC=CC=1>[C:28]1([C:19]2[C:20](=[O:27])[N:21]([CH2:24][CH2:25][CH3:26])[C:22](=[O:23])[N:16]3[CH2:15][CH:14]=[CH:13][S:18][C:17]=23)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: CCCn1c(=O)c(-c2ccccc2)c2n(c1=O)CCC(O)S2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCCn1c(=O)c(-c2ccccc2)c2n(c1=O)CC=CS2
Yield: 70 %

Procedure:
A catalytic amount of p-toluenesulfonic acid was added to a solution of 2-hydroxy-9-phenyl-7-propyl-3,4-dihydro2H,6H-pyrimido[6,1-b][1,3]thiazine-6,8(7H)-dione (0.5 g) in toluene (20 ml) and was refluxed for 5 hours. The reaction solution was concentrated to dryness, and the resulting residue was dissolved in methylene chloride. After washing with water and drying, the solution was concentrated to dryness. The resulting crude crystals were recrystalized from ethyl acetate-isopropyl ether to give colorless prisms (0.33 g, 70%).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12](Br)[CH:13]=1)(=[O:3])[CH3:2].[Cl:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1B(O)O>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:29]2[CH:30]=[CH:31][C:32]([F:34])=[CH:33][C:28]=2[Cl:27])[CH:13]=1)(=[O:3])[CH3:2]
Reactant: OB(O)c1ccc(F)cc1Cl
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(Br)c1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(-c2ccc(F)cc2Cl)c1

Procedure:
By following a procedure analogous to Example 27 starting from 5-bromo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside and 2-chloro-4-fluoro-phenylboronic acid, 5-(2-chloro-4-fluorophenyl)-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside is obtained in the form of an off-white foam (yield 81%).
Reaction SMILES: [O:1]=[C:2]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=1[NH:22][C:23](=O)[C@@H:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:25][CH3:26])[CH2:3][C:4](=[O:11])[NH:5][C:6]1[S:7][CH:8]=[CH:9][N:10]=1>CN(C)C1C=CN=CC=1.O1CCCC1>[OH:1][C:2]1[C:12]2[C:13](=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:16][CH:17]=2)[N:22]=[C:23]([C@@H:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:31])[CH3:32])[CH2:25][CH3:26])[C:3]=1[C:4]([NH:5][C:6]1[S:7][CH:8]=[CH:9][N:10]=1)=[O:11]
Reactant: CC[C@H](NC(=O)OC(C)(C)C)C(=O)Nc1c(C(=O)CC(=O)Nc2nccs2)cccc1C(F)(F)F
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CC[C@H](NC(=O)OC(C)(C)C)c1nc2c(C(F)(F)F)cccc2c(O)c1C(=O)Nc1nccs1
Yield: 88.1 %

Procedure:
Using the procedure of Step C of Example 3, 8 g of the product of Step B, 80 ml of tetrahydrofuran and 1.9 g of 4-dimethylaminopyridine were reacted to obtain 6.8 g of 1,1-dimethylethyl N-[(S) 1-[4-hydroxy-3-[(2-thiazolyl-amino)-carbonyl]-8-(trifluoromethyl]-quinolin-2-yl]-propyl]-carbamate melting at 260°-262° C. and having a specific rotation of [α]D =+66.5°±2.5° (c=0.7% in CH3COOH).
Reaction SMILES: [CH3:1][N:2]([CH3:38])[C@H:3]1[CH2:7][CH2:6][N:5]([C:8]([C@@H:10]2[CH2:14][C@H:13]([S:15]CC3C=CC(OC)=CC=3)[CH2:12][N:11]2[C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=2)=[O:26])=[O:9])[CH2:4]1.FC(F)(F)C(O)=O.[F:46][C:47]([F:53])([F:52])[S:48]([OH:51])(=[O:50])=[O:49]>C1(OC)C=CC=CC=1>[F:46][C:47]([F:53])([F:52])[S:48]([OH:51])(=[O:50])=[O:49].[CH3:1][N:2]([CH3:38])[C@H:3]1[CH2:7][CH2:6][N:5]([C:8]([C@@H:10]2[CH2:14][C@H:13]([SH:15])[CH2:12][N:11]2[C:25]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][C:32]([N+:35]([O-:37])=[O:36])=[CH:33][CH:34]=2)=[O:26])=[O:9])[CH2:4]1
Reactant: COc1ccc(CS[C@H]2C[C@@H](C(=O)N3CC[C@H](N(C)C)C3)N(C(=O)OCc3ccc([N+](=O)[O-])cc3)C2)cc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CN(C)[C@H]1CCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
845 mg of (2S,4S)-2-[(3S)-3-dimethylamino-1-pyrrolidinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine [prepared as described in step (1) above] were suspended in 1.7 ml of anisole, and 8.5 ml of trifluoroacetic acid and 0.28 ml of trifluoromethanesulfonic acid were added to the resulting suspension, whilst ice-cooling, after which the mixture was stirred at room temperature for 1 hour. The cycle comprising removing the solvent by evaporation under reduced pressure, washing the residue with hexane to remove anisole, adding diethyl ether to the mixture, cooling the mixture to -78° C. to solidify the product and milling the product, followed by decantation, was repeated several times to obtain 1.14 g of the title compound as a powder.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[C:8]([S:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N+:17]([O-])=O)[CH:7]=[CH:6][C:5]=1[NH:20][C:21](=[O:24])[CH2:22][CH3:23].[H][H]>C(OCC)(=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[C:8]([S:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH2:17])[CH:7]=[CH:6][C:5]=1[NH:20][C:21](=[O:24])[CH2:22][CH3:23]
Reactant: [H][H]
Reactant: CCC(=O)Nc1ccc(Sc2ccccc2[N+](=O)[O-])cc1C(=O)OC
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCC(=O)Nc1ccc(Sc2ccccc2N)cc1C(=O)OC

Procedure:
A mixture of 5-(2-nitro-phenylsulfanyl)-2-propionylamino-benzoic acid methyl ester (110 mg, 0.31 mmol, prepared according to Sevbo et al. 1976) and palladium-on-charcoal (10%, 25 mg) in ethyl acetate (5 mL) was stirred in an atmosphere of hydrogen (1 atm) at room temperature for 2 hours. The catalyst was filtered off and the solvent was removed by evaporation to yield the title compound quantitatively.
Reaction SMILES: Br[CH:2]([CH2:8][CH2:9][CH2:10]Br)[C:3]([O:5][CH2:6][CH3:7])=[O:4].C(=O)([O-])[O-].[K+].[K+].[CH2:18]([NH2:30])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].CO>C(O)C>[CH2:6]([O:5][C:3](=[O:4])[C@@H:2]1[CH2:8][CH2:9][CH2:10][N:30]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH3:7]
Reactant: CCOC(=O)C(Br)CCCBr
Reactant: CCCCCCCCCCCCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CCO
Product: CCCCCCCCCCCCN1CCC[C@H]1C(=O)OCC

Procedure:
In 150 ml of ethanol was dissolved 22.8 g of ethyl 2,5-dibromovalerate, and 15 g of potassium carbonate was suspended in the solution. To the suspension was added dropwise a methanolic solution of 18.5 g of laurylamine under ice-cooling. After the addition, the reaction mixture was allowed by react at a refluxing temperature of methanol for 5 hours to obtain N-dodecylproline ethyl ester.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12]C(=O)C)[O:8][C:7](=[O:16])[CH:6]=[C:5]2[CH:17]=[N+:18]=[N-:19]>CO.[Zn]>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][C:7](=[O:16])[CH:6]=[C:5]2[CH:17]=[N+:18]=[N-:19]
Reactant: CC(=O)Oc1cc2oc(=O)cc(C=[N+]=[N-])c2cc1Br
Agent: [Zn]
Solvent: CO
Product: [N-]=[N+]=Cc1cc(=O)oc2cc(O)c(Br)cc12
Temperature: 25 °C
Reaction time: 75 h
Yield: 100 %

Procedure:
A mixture of 43.0 mg (0.133 mmol) of compound 21 and 154.6 mg (2.36 mmol) of Zn in MeOH (10 mL) was stirred at room temperature for 75 hours under a N2 atmosphere. Zn was removed by filtration and washed thoroughly with MeOH. The combined organic layer was evaporated to yield 37.5 mg (0.133 mmol, 100% yield) of compound 22. MS (ES, positive) 282.7, 284.7.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:72][Si:73]([C:76]([CH3:79])([CH3:78])[CH3:77])([CH3:75])[CH3:74])[CH2:21][NH:22][C@H:23]([CH3:71])[CH2:24][C:25]2[CH:26]=[C:27]([CH2:31][CH2:32][NH:33][C:34]([CH2:36][C:37]3[CH:42]=[CH:41][C:40]([CH2:43][NH:44][C:45]([CH2:47][CH2:48][N:49]4[CH2:54][CH2:53][CH:52]([O:55][C:56](=[O:70])[NH:57][C:58]5[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=5[C:64]5[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=5)[CH2:51][CH2:50]4)=[O:46])=[CH:39][CH:38]=3)=[O:35])[CH:28]=[CH:29][CH:30]=2)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)C1C=CC=CC=1>CCO.[Pd]>[Si:73]([O:72][C@H:20]([C:12]1[CH:11]=[CH:10][C:9]([OH:8])=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16](=[O:19])[NH:17]2)[CH2:21][NH:22][C@H:23]([CH3:71])[CH2:24][C:25]1[CH:26]=[C:27]([CH2:31][CH2:32][NH:33][C:34]([CH2:36][C:37]2[CH:38]=[CH:39][C:40]([CH2:43][NH:44][C:45]([CH2:47][CH2:48][N:49]3[CH2:50][CH2:51][CH:52]([O:55][C:56](=[O:70])[NH:57][C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=4[C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=4)[CH2:53][CH2:54]3)=[O:46])=[CH:41][CH:42]=2)=[O:35])[CH:28]=[CH:29][CH:30]=1)([C:76]([CH3:77])([CH3:78])[CH3:79])([CH3:74])[CH3:75]
Reactant: C[C@H](Cc1cccc(CCNC(=O)Cc2ccc(CNC(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)cc2)c1)NC[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: [Pd]
Solvent: CCO
Product: C[C@H](Cc1cccc(CCNC(=O)Cc2ccc(CNC(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)cc2)c1)NC[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(O)c2[nH]c(=O)ccc12
Reaction time: 1 h

Procedure:
Dry nitrogen was bubbled into a stirred solution of biphenyl-2-ylcarbamic acid 1-{2-[(4-{[2-(3-{(R)-2-[(R)-2-(8-benzyloxy-2-oxo-1,2- dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)-ethylamino]propyl}phenyl)ethylcarbamoyl]-methyl}phenyl)methylcarbamoyl]ethyl}-piperidin-4-yl ester (0.704 g, 0.650 mmol) in EtOH (5.00 mL) for 3 min and then palladium on carbon (10 wt. %, ˜50% water; 0.289 g, 0.130 mmol) was added. Hydrogen was bubbled into the reaction mixture for 3 min and then the mixture was stirred under an atmosphere of hydrogen (balloon) for 1 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give the title compound, which was used without further purification in the next reaction.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](=[O:11])[CH3:10].[OH-].[K+]>C1(C)C(C)=CC=CC=1.C1C=CC=CC=1.C1C=CC=CC=1.Cl[Ru]Cl.Cl[Ru]Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([OH:11])[CH3:10]
Reactant: COc1ccccc1C(C)=O
Agent: Cl[Ru]Cl
Agent: [K+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: Cc1ccccc1C
Product: COc1ccccc1C(C)O
Temperature: 140 °C
Reaction time: 1 h

Procedure:
Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C6H5—, 2.6 μmol, 0.65 mol %) were dissolved in xylene (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 140° C. After the mixture was cooled to room temperature, o-methoxyacetophenone (0.4 mmol), xylene (2 mL) and an aqueous solution of potassium hydroxide (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H2 (3 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure (o-methoxyphenyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis.
Reaction SMILES: C[C:2]1[C:3]([N:11]=[C:12]=[O:13])=[CH:4][CH:5]=[CH:6][C:7]=1[N:8]=[C:9]=[O:10].[C:14]1(N=C=O)C=CC(N=C=O)=CC=1.[N-]=C=O.[N-]=C=O.C1(CC2C=CC=CC=2)C=CC=CC=1.C1(N=C=O)C=CC=C(N=C=O)C=1.C(N=C=O)CCCCCN=C=O.C(N=C=O)CCCN=C=O.COC1C=C(C2C=CC(N=C=O)=C(OC)C=2)C=CC=1N=C=O.CC1C=C(C2C=CC(N=C=O)=C(C)C=2)C=CC=1N=C=O.C1C=C(N=C=O)C2C=CC=C(N=C=O)C=2C=1.C1(CN=C=O)C=CC(CN=C=O)=CC=1.C1(CN=C=O)C=CC=C(CN=C=O)C=1.N(CC1CCCC(CN=C=O)C1)=C=O.N(CC1CCC(CN=C=O)CC1)=C=O.C1C(CC2CCC(N=C=O)CC2)CCC(N=C=O)C1.O=C=NC1CC(C)(C)CC(C)(CN=C=O)C1>>[CH3:14][C:4]1[C:3]([N:11]=[C:12]=[O:13])=[CH:2][C:7]([N:8]=[C:9]=[O:10])=[CH:6][CH:5]=1
Reactant: Cc1c(N=C=O)cccc1N=C=O
Reactant: O=C=Nc1ccc(N=C=O)cc1
Agent: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Agent: COc1cc(-c2ccc(N=C=O)c(OC)c2)ccc1N=C=O
Agent: Cc1cc(-c2ccc(N=C=O)c(C)c2)ccc1N=C=O
Solvent: c1ccc(Cc2ccccc2)cc1
Product: Cc1ccc(N=C=O)cc1N=C=O

Procedure:
2,6-tolylene diisocyanate; p-phenylene diisocyanate; diphenylmethane diisocyanate (may be abbreviated as "MDI"); m-phenylene diisocyanate; hexamethylene diisocyanate; tetramethylene diisocyanate; 3,3'-dimethoxy-4,4'-biphenylene diisocyanate; 2,4-naphthalene diisocyanate; 3,3'-dimethyl-4,4'-biphenylene diisocyanate; 4,4'-diphenylene diisocyanate; 4,4'-diisocyanato diphenyl ether; 1,5-naphthalene diisocyanate; p-xylylene diisocyanate; m-xylylene diisocyanate; 1,3-diisocyanato methylcyclohexane; 1,4-diisocyanato methylcyclohexane; 4,4'-diisocyanato dicyclohexane; 4,4'-diisocyanato dicyclohexylmethane; and isophorone diisocyanate.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([OH:9])=[C:4]([Cl:10])[N:3]=1.[C:11]([O:15][C:16](=[O:22])[N:17]([CH2:19][CH2:20]O)[CH3:18])([CH3:14])([CH3:13])[CH3:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCOCC1>[C:11]([O:15][C:16](=[O:22])[N:17]([CH3:18])[CH2:19][CH2:20][O:9][C:5]1[C:4]([Cl:10])=[N:3][C:2]([Cl:1])=[N:7][C:6]=1[Cl:8])([CH3:13])([CH3:14])[CH3:12]
Reactant: CN(CCO)C(=O)OC(C)(C)C
Reactant: Oc1c(Cl)nc(Cl)nc1Cl
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: CN(CCOc1c(Cl)nc(Cl)nc1Cl)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 124.5 %

Procedure:
A mixture of 2,4,6-trichloro-pyrimidin-5-ol (300 mg, 1.50 mmol), (2-hydroxy-ethyl)-methyl-carbamic acid tert-butyl ester (300 mg, 1.71 mmol), triphenylphosphine (455 mg, 1.73 mmol) and DIAD (339 μL, 1.73 mmol) in dioxane (2.5 mL) was stirred at RT for 1.5 hours then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0-50% ethyl acetate in cyclohexane) affording Methyl-[2-(2,4,6-trichloro-pyrimidin-5-yloxy)-ethyl]-carbamic acid tert-butyl ester (666 mg, quantitative). LCMS: RT=3.09 min, [M-Boc+Na]+=279.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[CH:9]1([CH2:12][NH2:13])[CH2:11][CH2:10]1>CCN(C(C)C)C(C)C>[Br:8][C:4]1[N:3]=[C:2]([NH:13][CH2:12][CH:9]2[CH2:11][CH2:10]2)[CH:7]=[CH:6][CH:5]=1
Reactant: Brc1cccc(Br)n1
Reactant: NCC1CC1
Solvent: CCN(C(C)C)C(C)C
Product: Brc1cccc(NCC2CC2)n1
Yield: 82.4 %

Procedure:
A solution of 2,6-dibromopyridine (33.0 g, 139 mmol) and cyclopropanemethylamine (10.8 g, 153 mmol) in DIPEA (27 mL) was heated at reflux for 24 h in a sealed pressure tube. The reaction mixture was cooled, concentrated in vacuo, and the residue was partitioned between EtOAc (250 mL) and saturated aqueous NaHCO3 (200 mL). The organic layer was washed with water (200 mL) followed by brine (200 mL) and dried (Na2SO4). The organic layer was filtered, concentrated in vacuo, and purified by flash chromatography (silica, 10% EtOAc/hexanes) affording 26 g of amine 2-1 as a white solid in 82% yield.