Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][SiH:2]([Cl:4])[Cl:3].[CH2:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl.CC(O)C>[CH3:1][Si:2]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])([Cl:4])[Cl:3]
Reactant: C[SiH](Cl)Cl
Reactant: C=CCCCCCCCC
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: CCCCCCCCCC[Si](C)(Cl)Cl
Yield: 94 %

Procedure:
2.25 Parts of methyl dichlorosilane, 4.04 parts of 1-decene and a solution containing about 0.0005 part of chloroplatinic acid catalyst in 0.006 part of 2-propanol were charged to a reaction vessel and heated to about 100°-120° C. for six hours. The product was vacuum distilled at 110°-114° C. at 1-3 Torr. 4.7 Parts (94% yield) of methyl decyl dichlorosilane was obtained.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Cl[C:18]1[C:27]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[N:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:35]([O:37][CH3:38])=[O:36])[CH:24]=2)[N:19]=1.CCN(C(C)C)C(C)C>CN(C)C=O>[F:34][C:31]1[CH:30]=[CH:29][C:28]([C:27]2[C:18]([N:12]3[CH2:11][CH2:10][CH:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=4)[CH2:14][CH2:13]3)=[N:19][C:20]3[C:25]([N:26]=2)=[CH:24][C:23]([C:35]([O:37][CH3:38])=[O:36])=[CH:22][CH:21]=3)=[CH:33][CH:32]=1
Reactant: COC(=O)c1ccc2nc(Cl)c(-c3ccc(F)cc3)nc2c1
Reactant: FC(F)(F)c1ccc(C2CCNCC2)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(N3CCC(c4ccc(C(F)(F)F)cc4)CC3)c(-c3ccc(F)cc3)nc2c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Into a 20-mL sealed tube, was placed a solution of 4-(4-(trifluoromethyl)phenyl)piperidine (420 mg, 1.83 mmol, 3.00 equiv), methyl 2-chloro-3-(4-fluorophenyl)quinoxaline-6-carboxylate (150 mg, 0.47 mmol, 1.00 equiv), DIEA (305 mg, 2.36 mmol, 5.00 equiv) in N,N-dimethylformamide (10 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 200 mg (83%) of methyl 3-(4-fluorophenyl)-2-(4-(4-(trifluoromethyl)phenyl)piperidin-1-yl)quinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: [C:1](Cl)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[NH2:9][C:10]1[CH:11]=[CH:12][C:13]2[O:18][CH2:17][CH2:16][N:15]([CH2:19][C:20]3[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=3)[C:23]([O:25][CH3:26])=[O:24])[C:14]=2[CH:30]=1.CN1CCOCC1>ClCCl>[C:1]([NH:9][C:10]1[CH:11]=[CH:12][C:13]2[O:18][CH2:17][CH2:16][N:15]([CH2:19][C:20]3[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=3)[C:23]([O:25][CH3:26])=[O:24])[C:14]=2[CH:30]=1)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCC(=O)Cl
Reactant: COC(=O)c1cccc(CN2CCOc3ccc(N)cc32)c1
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CCCCCC(=O)Nc1ccc2c(c1)N(Cc1cccc(C(=O)OC)c1)CCO2
Reaction time: 0.5 h

Procedure:
Hexanoyl chloride (0.135 g.) was added dropwise to a stirred solution of methyl 3-(6-amino-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)benzoate (X) (0.3 g.), and N-methylmorpholine (0.101 g.) in dichloromethane (30 ml.). After 0.5 hours, the mixture was diluted with dichloromethane, washed with water, dried (MgSO4) and evaporated to give an oil which was filtered through a short column of silica gel using 35:65 v/v ethyl acetate:hexane to give the title compound as a syrup; partial NMR (80 MHz, CDCl3): 0.8-1.9[complex m,9H, CH3 (CH2)3 ]; 2.2(m,2H, CH2CONH); 3.3(m,2H, N.CH2.CH2.O); 3.9(s,3H, OMe); 4.2(m,2H, N.CH2.CH2O); 4.5(s,2H, N.CH2Ar).
Reaction SMILES: C1(OC)C=CC=CC=1.COC1C=CC(C[O:16][C:17](=[O:64])[CH:18]([NH:33][C:34]([NH:36][CH:37]([C:52]([O:54]CC2C=CC(OC)=CC=2)=[O:53])[CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:51])[C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)=[O:35])[CH2:19][CH2:20][C:21]([O:23]CC2C=CC(OC)=CC=2)=[O:22])=CC=1>C(O)(C(F)(F)F)=O>[C:52]([CH:37]([NH:36][C:34](=[O:35])[NH:33][CH:18]([CH2:19][CH2:20][C:21]([OH:23])=[O:22])[C:17]([OH:64])=[O:16])[CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:51])[C:44]1[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=1)([OH:54])=[O:53]
Reactant: COc1ccc(COC(=O)CCC(NC(=O)NC(CCCCNC(=O)c2ccc(F)cc2)C(=O)OCc2ccc(OC)cc2)C(=O)OCc2ccc(OC)cc2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: O=C(O)CCC(NC(=O)NC(CCCCNC(=O)c1ccc(F)cc1)C(=O)O)C(=O)O
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 79.3 %

Procedure:
A solution of 3% anisole in TFA (15 mL) was added to 5 (0.081 g, 0.1 mmol) at 0° C. The mixture was stirred at room temperature for 20 min then concentrated on a rotary evaporator. The crude material was purified by HPLC (Econosil C18 10 μm, 250×10 mm, H2O/CH3CN/TFA (75/25/0.1), 4 mL/min, with purified 6 eluting at about 9 min) to afford 0.035 g (79%) of 6. 1H NMR (400 MHz, D2O) δ 7.66-7.69 (m, 2H), 7.11-7.16 (m, 2H), 4.12-4.19 (m, 2H), 3.28-3.31 (m, 2H), 2.39-2.43 (m, 2H), 2.07-2.09 (m, 1H), 1.79-1.90 (m, 2H), 1.55-1.69 (m, 3H), 1.39-1.40 (m, 2H). ESI-Mass calcd for C19H24FN3O8Na [M+Na]+ 464.1, found 464.4. FAB-HRMS calcd for C19H25FN3O8 [M+H]+ 442.1626, found 442.1646.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1I.C([Mg]Br)(C)C.[CH3:15][CH2:16][C:17](=[O:20])[CH2:18][CH3:19].CC(=O)OCC>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:17]([OH:20])([CH2:18][CH3:19])[CH2:16][CH3:15]
Reactant: CCC(=O)CC
Reactant: Cc1ccc(Br)c(I)c1
Agent: CC(C)[Mg]Br
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCC(O)(CC)c1cc(C)ccc1Br
Temperature: -10 °C
Reaction time: 1 h
Yield: 26.9 %

Procedure:
To a solution of 1-bromo-2-iodo-4-methylbenzene (28 g, 94 mmol) in THF (10 ml) at −10° C. under nitrogen was slowly added i-PrMgBr (47 ml, 94 mmol). The reaction mixture was stirred for 1 h at −10° C. Then the reaction mixture was cooled to −30° C., and pentan-3-one (8.1 g, 94 mmol) was added dropwise. The reaction mixture was stirred for 1 h at −30° C. under nitrogen and then warmed to rt and stirred for additional 2 h. Then the reaction mixture was quenched with 2N HCl solution and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (10:0 to 5:1) to give the desired compound (6.5 g, yield 26.9%) as colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.52-7.50 (d, 1H), 7.43-7.40 (d, 1H), 6.95-6.92 (d, 1H), 2.48-2.40 (q, 2H), 2.31 (s, 3H), 1.86-1.78 (q, 2H), 0.77-0.71 (m, 6H). MS: m/z=257 and 259 [M+1]+.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][S:5][CH:6]=1.[O:7]1[C:11]2([CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]2)[O:10][CH2:9][CH2:8]1>>[CH3:1][C:2]1[N:3]=[C:4]([C:14]2([OH:17])[CH2:15][CH2:16][C:11]3([O:10][CH2:9][CH2:8][O:7]3)[CH2:12][CH2:13]2)[S:5][CH:6]=1
Reactant: O=C1CCC2(CC1)OCCO2
Reactant: Cc1cscn1
Product: Cc1csc(C2(O)CCC3(CC2)OCCO3)n1

Procedure:
The title compound was prepared as a white solid from 4-methyl-thiazole (Aldrich) and 1,4-dioxa-spiro[4.5]decan-8-one using the procedure described in Step A of Example 33.
Reaction SMILES: [C:1]([O:5][C:6]([C@H:8]1[CH2:10][C@@H:9]1[CH:11]1[CH2:15][CH2:14][N:13](O)[C:12]1=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[OH-].[Na+]>[Cl-].[Cl-].[Cl-].[Ti+3].O>[C:1]([O:5][C:6]([C@H:8]1[CH2:10][C@@H:9]1[CH:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:17])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)[C@H]1C[C@@H]1C1CCN(O)C1=O
Agent: [Ti+3]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)[C@H]1C[C@@H]1C1CCNC1=O
Reaction time: 1.5 h
Yield: 88.6 %

Procedure:
To 100 ml of a solution of 1.85 g of the resulting 3-[(1R,2S)-2-t-butoxycarbonylcyclopropyl]-1-hydroxypyrrolidin-2-one in a 3:1 mixed solvent of methanol and water was added 4.45 ml of a titanium trichloride solution at room temperature while maintaining the reaction mixture neutral by addition of a 1N sodium hydroxide aqueous solution, followed by stirring at the same temperature for 1.5 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give 1.53 g (88.4%) of 3-[(1R,2S)-2-t-butoxycarbonylcyclopropyl]pyrrolidin-2-one.
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:14][C@@H:13]([OH:15])[CH2:12][CH2:11][C@@H:10]1[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si](O[C@@H]1C[C@@H](O)CC[C@H]1NC(=O)OC(C)(C)C)(C(C)(C)C)(C)C>>[Si:1]([O:8][C@H:9]1[CH2:14][C:13](=[O:15])[CH2:12][CH2:11][C@@H:10]1[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](O)C[C@@H]1O[Si](C)(C)C(C)(C)C
Agent: CC(C)(C)OC(=O)N[C@@H]1CC[C@H](O)C[C@H]1O[Si](C)(C)C(C)(C)C
Product: CC(C)(C)OC(=O)N[C@H]1CCC(=O)C[C@@H]1O[Si](C)(C)C(C)(C)C

Procedure:
tert-Butyl (1S,2S)-2-(tert-butyldimethylsilyloxy)-4-oxocyclohexylcarbamate was prepared from tert-butyl (1S,2S,4S)-2-(tert-butyldimethylsilyloxy)-4-hydroxycyclohexylcarbamate (41A) as described in 40A. It was converted to the product as described in 40A.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][CH3:12])[CH2:2][CH3:3].Br[N:14]1C(=O)CC[C:15]1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.CNN>CCOCC.C(Cl)(Cl)(Cl)Cl>[CH2:2]([C:1]1[N:14]([CH3:15])[C:10]([CH2:11][CH3:12])=[C:5]2[C:4]=1[CH:9]=[CH:8][CH:7]=[CH:6]2)[CH3:3]
Reactant: CCCc1ccccc1CCC
Reactant: O=C1CCC(=O)N1Br
Agent: CNN
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOCC
Product: CCc1c2ccccc2c(CC)n1C

Procedure:
A mixture of 0.374 mole of o-dipropylbenzene, 146 g. (0.822 mole) of N-bromosuccinimide, 0.1 g. of benzoyl peroxide, and 800 ml. of carbon tetrachloride is heated under reflux with stirring and ultraviolet irradiation until the reaction is complete. The precipitated succinimide is filtered, washed with carbon tetrachloride, and the filtrate is evaporated to dryness under reduced pressure. The residual α,α'-dibromo-o-dipropylbenzene is dissolved in 800 ml. of absolute ether. To the stirred solution under nitrogen is added dropwise a solution of 40 g. (0.87 mole) of methyl hydrazine in 50 ml. of absolute ether. A gummy precipitate separates. After 3 hours of stirring and an overnight period of standing, the ether is decanted. The residue dissolved in 625 ml. of water is treated with 375 ml. of 40% sodium hydroxide solution and the mixture is stirred at reflux for 1.5 hours. After cooling, the precipitate of the crude product is collected, washed with water, and dissolved in 600 ml. of ether. The ether solution is washed repeatedly with water and dried over anhydrous magnesium sulfate with stirring and cooling in an ice bath. The filtered solution is evaporated under reduced pressure and the residual dark yellow solid is triturated with petroleum ether, filtered and dried in vacuo to yield 1,3-diethyl-2-methylisoindole.
Reaction SMILES: [CH3:1][N:2]([CH3:18])[C:3]([C:5]([NH:10]C(=O)OC(C)(C)C)([CH2:8][CH3:9])[CH2:6][CH3:7])=[O:4].[ClH:19]>C(OCC)(=O)C>[ClH:19].[NH2:10][C:5]([CH2:8][CH3:9])([CH2:6][CH3:7])[C:3]([N:2]([CH3:18])[CH3:1])=[O:4]
Reactant: CCC(CC)(NC(=O)OC(C)(C)C)C(=O)N(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: CCC(N)(CC)C(=O)N(C)C
Reaction time: 8 h

Procedure:
tert-Butyl 3-(dimethylcarbamoyl)pentan-3-ylcarbamate (0.12 g, 0.47 mmol) was added to a saturated solution of hydrochloride in ethyl acetate (5 mL) and the mixture was stirred overnight. The solvent was removed by reduced pressure to give the crude product (0.1 g); MS (EI): m/e=159.2 [M+H]+.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[N:10]([C:11]([C:13]2[N:14]=[C:15]([CH3:25])[S:16][C:17]=2[C:18]2[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=2)=[O:12])[CH2:9][C@H:8]2[C@@H:4]1[CH2:5][CH:6]([CH3:26])[CH2:7]2.[CH3:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([CH:36]=1)[C:33](O)=[O:34]>>[CH3:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([CH:36]=1)[C:33]([NH:1][CH2:2][C@H:3]1[N:10]([C:11]([C:13]2[N:14]=[C:15]([CH3:25])[S:16][C:17]=2[C:18]2[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=2)=[O:12])[CH2:9][C@H:8]2[C@@H:4]1[CH2:5][CH:6]([CH3:26])[CH2:7]2)=[O:34]
Reactant: Cc1cncc(C(=O)O)c1
Reactant: Cc1cccc(-c2sc(C)nc2C(=O)N2C[C@@H]3CC(C)C[C@@H]3[C@H]2CN)c1
Product: Cc1cncc(C(=O)NC[C@@H]2[C@H]3CC(C)C[C@H]3CN2C(=O)c2nc(C)sc2-c2cccc(C)c2)c1

Procedure:
prepared by reaction of [(1S,2S,5R)-2-aminomethyl-7-methyl-3-aza-bicyclo[3.3.0]oct-3-yl]-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone with 5-methyl-nicotinic acid.
Reaction SMILES: CON(C)[C:4](=[O:15])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[N:7][CH:6]=1.[CH:17]1([Mg]Br)[CH2:19][CH2:18]1>O1CCCC1>[CH:17]1([C:4]([C:5]2[CH:6]=[N:7][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:10]=2)=[O:15])[CH2:19][CH2:18]1
Reactant: Br[Mg]C1CC1
Reactant: CON(C)C(=O)c1ccc(C(F)(F)F)nc1
Solvent: C1CCOC1
Product: O=C(c1ccc(C(F)(F)F)nc1)C1CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide (1.00 g, 4.27 mmol) in tetrahydrofuran (30 mL) at 0° C. was added 0.5 M of cyclopropylmagnesium bromide in tetrahydrofuran (20 μL, 0.01 mol) dropwise over 15 minutes. The mixture was stirred at 0° C. for 30 minutes then at room temperature overnight. The reaction was quenched with 1N HCl. Solvent was removed and the aqueous layer was extracted with ethyl acetate. Thr organic layers were combined and dried with MgSO4, filtered and concentrated. The crude product was purified by silica gel column (0-60% ethyl acetate/hexane) to obtain a pale yellow solid.
Reaction SMILES: Cl.C(O[C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[C:10]2[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[NH:6])C.C[O-].[Na+].[NH2:26][NH:27][C:28](=O)[CH2:29][N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>C(O)C.CO>[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([C:5]4[N:6]=[C:28]([CH2:29][N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)[NH:27][N:26]=4)[CH:8]=3)[NH:12][N:11]=2)=[CH:21][CH:20]=1
Reactant: CCOC(=N)c1ccc2[nH]nc(-c3ccc(F)cc3)c2c1
Reactant: NNC(=O)CN1CCOCC1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: Fc1ccc(-c2n[nH]c3ccc(-c4n[nH]c(CN5CCOCC5)n4)cc23)cc1
Temperature: 0 °C
Yield: 5 %

Procedure:
A suspension of ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride (0.300 g, 0.94 mmol) in 4 mL of anhydrous ethanol was prepared and cooled to 0° C. An excess of a freshly prepared solution of sodium methoxide in methanol (1.41 mL, 2.0 M)) was added followed by 3 equivalents of N-amino-2-morpholin-4-ylacetamide (0.449 g, 2.82 mmol) as a solid. The reaction mixture was heated to reflux temperature in a sealed tube for 2 days. The reaction was then quenched with water, the pH adjusted to neutral and the crude product extracted with ethyl acetate. The components of the crude mixture were separated by preparative HPLC (title compound: 0.017 g, 5% yield): 1H NMR (CD3OD) δ 8.71 (d, 1H), 8.08-8.03 (m, 3H), 7.68 (d, 1H), 7.3 (t, 2H), 3.73 (m, 6H), 2.59 (m, 4H); ES-MS (m/z) 379 [M+H]+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1/[C:9](=[CH:14]\[O:15][CH3:16])/[C:10]([O:12][CH3:13])=[O:11].[C:17](Cl)([Cl:19])=[O:18].O>C1(C)C=CC=CC=1>[Cl:19][C:17]([O:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1/[C:9](=[CH:14]\[O:15][CH3:16])/[C:10]([O:12][CH3:13])=[O:11])=[O:18]
Reactant: CO/C=C(/C(=O)OC)c1ccccc1CO
Reactant: O=C(Cl)Cl
Solvent: Cc1ccccc1
Solvent: O
Product: CO/C=C(/C(=O)OC)c1ccccc1COC(=O)Cl
Reaction time: 3 h
Yield: 13 %

Procedure:
A solution of (E)-methyl 2-[2-(hydroxymethyl)phenyl]-3-methoxypropenoate (1 g) in toluene (10 ml) was added slowly to a solution of phosgene in toluene (12.5 w/w, 6.5 ml). After stirring for 3 hours, water (70 ml) was added and the resulting mixture was extracted with diethyl ether. The diethyl ether extract was washed with brine, dried over anhydrous sodium sulphate and evaporated under reduced pressure to leave an oil. The oil was purified by chromatography on silica gel, eluting with 30% ethyl acetate/hexane to give (E)-methyl 2-[2-(chloroformyloxymethyl)phenyl]-3-methoxypropenoate (0.163 g, 13%). 1H NMR (CDCl3): 3.7(s,3H), 3.8(s,3H), 4.5(s,2H), 7.1-7.5(m,4H), 7.6(s,1H) ppm. IR (film): 1631, 1707, 1774 cm-1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)=[CH:4][CH:3]=1.[CH3:17][N:18]1[C:22]([C:23]2[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=2)[NH2:26])=[CH:21][N:20]=[C:19]1[CH3:30].Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:30][C:19]1[N:18]([CH3:17])[C:22]([C:23]2[CH:24]=[C:25]([NH:26][C:11]([C:10]3[CH:9]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH:16]=[CH:15][CH:14]=3)=[O:13])[CH:27]=[CH:28][CH:29]=2)=[CH:21][N:20]=1
Reactant: O=C(O)c1cccc(-c2ccc(F)cc2)c1
Reactant: Cc1ncc(-c2cccc(N)c2)n1C
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: Cc1ncc(-c2cccc(NC(=O)c3cccc(-c4ccc(F)cc4)c3)c2)n1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 89.2 %

Procedure:
To a suspension of 3-(4-fluorophenyl)benzoic acid (151 mg) and 3-(1,2-dimethylimidazol-5-yl)aniline (131 mg) in dichloromethane (5 ml) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (201 mg) and 4-dimethylaminopyridine (43 mg). The mixture was stirred at ambient temperature for 18 hours and diluted with dichloromethane. The solution was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by a silica gel column chromatography eluting with 3% methanol in dichloromethane to give N-[3-(2,3 dimethyl-3H-imidazolyl)-phenyl]-4′-fluoro-biphenyl-3-carboxamide (240 mg, 88.9%).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:6][N:7]=1.[CH3:11][C:12]1[N:17]=[C:16]([SH:18])[N:15]=[C:14]([OH:19])[CH:13]=1>>[CH3:11][C:12]1[N:17]=[C:16]([S:18][CH2:2][C:3]2[N:4]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:6][N:7]=2)[N:15]=[C:14]([OH:19])[CH:13]=1
Reactant: CC(C)n1ccnc1CCl
Reactant: Cc1cc(O)nc(S)n1
Product: Cc1cc(O)nc(SCc2nccn2C(C)C)n1
Yield: 72 %

Procedure:
This example was synthesized from 2-(chloromethyl)-1-(propan-2-yl)-1H-imidazole and 6-methyl-2-sulfanylpyrimidin-4-ol following the general procedure as shown in the last step of Example 109. This provided the title compound as a pale white solid (1.0 g, 72% yield); 1H NMR (400 MHz, DMSO-d6): δ 1.33 (m, 6H), 2.18 (s, 3H), 4.52 (s, 2H), 4.54 (m, 1H), 4.54 (m, 1H), 6.00 (br, 1H), 6.83 (s, 1H), 7.26 (s, 1H); M+265.
Reaction SMILES: [ClH:1].[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([S:11]([N:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH2:24][C:25]([N:27]4[CH2:36][CH2:35][C:30]5([CH2:34][NH:33][CH2:32][CH2:31]5)[CH2:29][CH2:28]4)=[O:26])[CH:22]=3)[CH2:17][CH2:16][CH2:15]2)(=[O:13])=[O:12])=[C:6]([CH3:37])[CH:5]=1.C(N(CC)CC)C.[C:45]1(=O)[CH2:48][CH2:47][CH2:46]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl.ClCCl.C(=O)([O-])O.[Na+]>[ClH:1].[CH:45]1([N:33]2[CH2:32][CH2:31][C:30]3([CH2:29][CH2:28][N:27]([C:25](=[O:26])[CH2:24][C:21]4[CH:22]=[C:23]5[C:18]([CH2:17][CH2:16][CH2:15][N:14]5[S:11]([C:7]5[C:6]([CH3:37])=[CH:5][C:4]([O:3][CH3:2])=[CH:9][C:8]=5[CH3:10])(=[O:12])=[O:13])=[CH:19][CH:20]=4)[CH2:36][CH2:35]3)[CH2:34]2)[CH2:48][CH2:47][CH2:46]1
Reactant: COc1cc(C)c(S(=O)(=O)N2CCCc3ccc(CC(=O)N4CCC5(CCNC5)CC4)cc32)c(C)c1
Reactant: O=C1CCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: O=C([O-])O
Solvent: CC(=O)O
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: COc1cc(C)c(S(=O)(=O)N2CCCc3ccc(CC(=O)N4CCC5(CC4)CCN(C4CCC4)C5)cc32)c(C)c1
Reaction time: 15 h

Procedure:
2-(1-(4-Methoxy-2,6-dimethylphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone hydrochloride (from stage (ii)) (140 mg, 0.255 mmol), triethylamine (0.04 ml, 0.255 mmol) and cyclobutanone (0.02 ml, 0.255 mmol) were dissolved in 1,2-dichloroethane (5 ml), and sodium triacetoxy-borohydride (75 mg, 0.358 mmol) and glacial acetic acid (15 mg, 0.255 mmol) were added thereto. The reaction mixture was stirred for 15 h and then diluted with dichloromethane, and saturated sodium hydrogen carbonate solution (10 ml) was added thereto. After phase separation, the aqueous phase was extracted with dichloromethane (3×30 ml). The combined organic phases were washed with saturated sodium chloride solution (30 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/dichloromethane/methanol/ammonia (25% aq.), 300:100:25:1). Finally, the hydrochloride was precipitated from ethereal solution (plus a small amount of acetone) with hydrogen chloride in ether (2 M) and the desired exemplary compound G-10 was thus obtained. Yield: 100 mg (65%). MS, Rt=3.4 min; m/z=566.1 [MH]+
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([CH2:25][N:26]([CH:35]=[O:36])[O:27]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N+:19]=3[O-:24])=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[OH-].[OH-].[Pd+2]>[CH:1]1([CH2:6][C@H:7]([CH2:25][N:26]([CH:35]=[O:36])[OH:27])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N+:19]=3[O-:24])=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=CN(C[C@@H](CC1CCCC1)C(=O)N1N=CC[C@H]1C(=O)Nc1cccc[n+]1[O-])OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: O=CN(O)C[C@@H](CC1CCCC1)C(=O)N1N=CC[C@H]1C(=O)Nc1cccc[n+]1[O-]
Reaction time: 0.58 h

Procedure:
In a 50 mL round-bottomed flask was added (5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(1-oxido-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (67 mg, 0.136 mmol) in methanol (3 ml), followed by Pearlman's catalyst (7 mg). The mixture was stirred under a balloon of H2 for 35 min, then catalyst was filtered off. Removal of the solvent provided (5S)-1-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(1-oxido-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide as a colorless oil. (27 mg, 48%). LCMS: (M+H)+: 404.3. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.04-1.26 (m, 2H) 1.40-1.70 (m, 5H) 1.70-2.00 (m, 4H) 3.35-3.45 (m, 1H) 3.50-3.75 (m, 2H) 3.76-4.04 (m, 2H) 5.10-5.37 (m, 1H) 7.09-7.34 (m, 2H) 7.49-7.67 (m, 1H) 7.91 (s, 1H) 8.35 (d, J=6.57 Hz, 1H) 8.46 (dd, J=8.46, 1.64 Hz, 1H)