Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg][Cl:25])(C)C.[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[C:39](Cl)[CH:40]=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:43][O:44][C:45]1[CH:50]=[C:49]([F:51])[C:48]([CH:52]=[O:53])=[CH:47][C:46]=1[O:54][CH3:55])=[O:32])([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[CH:39][C:40]([Cl:25])=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:43][O:44][C:45]1[CH:50]=[C:49]([F:51])[C:48]([CH:52]([OH:53])[C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[CH:47][C:46]=1[O:54][CH3:55])=[O:32])([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)[Mg]Cl
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1cc(I)c2cccnc21
Reactant: COc1cc(C=O)c(F)cc1OCc1nc2ccc(Cl)cc2n1C(=O)OC(C)(C)C
Solvent: C1CCOC1
Product: COc1cc(C(O)c2cn([Si](C(C)C)(C(C)C)C(C)C)c3ncccc23)c(F)cc1OCc1nc2cc(Cl)ccc2n1C(=O)OC(C)(C)C
Temperature: -5 °C
Yield: 44 %

Procedure:
3-Iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (68, 0.200 g, 0.5 mmol, prepared as described in Example 22) was dissolved in tetrahydrofuran (3 mL, 40 mmol). After the reaction reached the temperature of −20° C., a solution of 2M of isopropylmagnesium chloride in tetrahydrofuran (300 μL) was added dropwise. The resulted mixture was stirred to −5° C. After cooling the reaction to −20° C., a solution of 6-chloro-2-(5-fluoro-4-formyl-2-methoxy-phenoxymethyl)-benzoimidazole-1-carboxylic acid tert-butyl ester (152, 0.2 g, 0.46 mmol) in tetrahydrofuran (4 mL) was added at once to the mixture. The reaction warmed to −5° C. and was then evaporated to dryness under reduced pressure. Ethyl acetate was added. The organic portion was washed with saturated sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated. Purification with silica gel flash chromatography eluting with a gradient of ethyl acetate (5 to 80%) in hexanes gave the desired compound (153, 0.142 g, 44%). MS (ESI) [M+H+]+=709.4.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[C:11](=[O:20])[NH:12][CH2:13][CH:14]=[C:15]([CH2:16][C:17](O)=[O:18])[C:5]2=1.C(N(CC)CC)C.C1(P([N:42]=[N+:43]=[N-:44])(C2C=CC=CC=2)=O)C=CC=CC=1.C(OCC)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[C:11](=[O:20])[NH:12][CH2:13][CH:14]=[C:15]([CH2:16][C:17]([N:42]=[N+:43]=[N-:44])=[O:18])[C:5]2=1
Reactant: O=C(O)CC1=CCNC(=O)c2[nH]c3ccc(F)cc3c21
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOCC
Product: [N-]=[N+]=NC(=O)CC1=CCNC(=O)c2[nH]c3ccc(F)cc3c21
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To an ice-cold solution of (7-fluoro-1-oxo-1,2,3,10-tetrahydro-azepino[3,4-b]indol-5-yl)-acetic acid (0.99 g, 3.6 mmol) and triethylamine (0.36 g, 3.6 mmol) in dry DMF (10 mL) was added in dropwise a solution of diphenylphosphoryl azide (0.99 g, 3.6 mmol), in DMF (5 mL) over a period of 2 h. After removal of the cooling bath, the mixture was stirred at room temperature for 12 h. It was poured into ice and the precipitate therefore formed was collected by vacuum filtration, which appeared to be the title compound (0.10 g). Extract the rest part of the mixture with ethyl acetate (20 mL×2). The organic layers were combined, washed with saturated aqueous NaHCO3, brine, and dried over anhydrous Na2SO4. It was concentrated and the oil obtained was treated with diethyl ether to give additional title compound as a solid precipitate (0.23 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-:14])=[O:13])=[C:5]2Cl.Cl.[CH3:17][C:18]1([NH2:24])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(N(CC)CC)C.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([N+:12]([O-:14])=[O:13])=[C:5]2[NH:24][C:18]1([CH3:17])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1
Reactant: CC1(N)CCOCC1
Reactant: O=[N+]([O-])c1cnc2ccc(Br)cc2c1Cl
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC1(Nc2c([N+](=O)[O-])cnc3ccc(Br)cc23)CCOCC1
Yield: 84 %

Procedure:
A solution of 6-bromo-4-chloro-3-nitroquinoline (1 g, 3.48 mmol), 4-methyltetrahydro-2H-pyran-4-amine hydrochloride (1.055 g, 6.96 mmol) and triethylamine (1.939 mL, 13.91 mmol) in DMF (10 mL) was heated to 100° C. for 1 h in a sealed tube in the microwave reactor. The mixture was allowed to cool then poured into stirred water (50 mL) and the resulting yellow precipitate was collected by filtration and dried under vacuum to afford the desired material (1.070 g, 84%) as a yellow solid. This was used without further purification. NMR Spectrum: 1H NMR (400 MHz, DMSO-d6) δ 1.40 (3H, s), 1.78 (2H, dt), 1.89 (2H, ddd), 3.51-3.64 (4H, m), 7.80 (1H, s), 7.91 (1H, d), 8.01 (1H, dd), 8.48 (1H, d), 9.18 (1H, s). Mass Spectrum: m/z (ES+)[M+H]+=366, 368.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[S:32]1[CH:36]=[CH:35][C:34]([C:37]([CH2:39][N:40]2[C:46]3[CH:47]=[C:48]([CH3:51])[CH:49]=[CH:50][C:45]=3[N:44]([C:52](=[O:57])[C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:43][CH:42]([NH2:58])[C:41]2=[O:59])=[O:38])=[CH:33]1>O1CCCC1.O>[S:32]1[CH:36]=[CH:35][C:34]([C:37]([CH2:39][N:40]2[C:46]3[CH:47]=[C:48]([CH3:51])[CH:49]=[CH:50][C:45]=3[N:44]([C:52](=[O:57])[C:53]([CH3:54])([CH3:55])[CH3:56])[CH2:43][CH:42]([NH:58][C:14]([NH:1][C:2]3[CH:12]=[CH:11][CH:10]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:3]=3)=[O:16])[C:41]2=[O:59])=[O:38])=[CH:33]1
Reactant: CCOC(=O)c1cccc(N)c1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Cc1ccc2c(c1)N(CC(=O)c1ccsc1)C(=O)C(N)CN2C(=O)C(C)(C)C
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1cccc(NC(=O)NC2CN(C(=O)C(C)(C)C)c3ccc(C)cc3N(CC(=O)c3ccsc3)C2=O)c1
Reaction time: 0.17 h
Yield: 196.4 %

Procedure:
Ethyl 3-aminobenzoate (0.33 g) was dissolved in tetrahydrofuran (20 ml) and cooled on ice. Triphosgene (0.22 g) was added at internal temperature 5° C., triethylamine (0.76 g) was added dropwise thereto over 10 minutes period, the mixture was allowed to come to room temperature,stirred for 10 minutes. A solution of 1-(thiophen-3-yl)carbonylmethyl-2-oxo-3-amino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (0.69 g) in tetrahydrofuran (10 ml) was added, the resultant mixture was stirred for one hour. Water was added to the reaction mixture, extracted with methylene chloride, the organic layer was successively washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=1:1), to thereby obtain 0.86 g of the titled compound as pale brown crystals (Yield: 75%).
Reaction SMILES: CO.[N:3]1[N:4]=[C:5]([CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14]C)=[O:13])[NH:6][CH:7]=1.[OH-].[Li+].Cl>O.O1CCCC1>[N:3]1[N:4]=[C:5]([CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])[NH:6][CH:7]=1
Reactant: COC(=O)CCCCc1nnc[nH]1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)CCCCc1nnc[nH]1
Temperature: 0 °C
Yield: 346.4 %

Procedure:
Add methanol (3 mL), tetrahydrofuran (3 mL), and water (2 mL) to a flask containing methyl 5-(4H-1,2,4-triazol-3-yl)pentanoate (0.5 g; 1.0 equiv; 2.73 mmoles). Add lithium hydroxide (0.261 g; 4.0 equiv; 10.92 mmoles) in one portion, and stir at room temperature for 90 minutes. Cool the solution to 0° C. and add 5N hydrogen chloride (2.18 mL; 4.0 equiv; 10.92 mmoles) slowly. Concentrate the mixture and then azeotrope the residue with toluene (4×10 mL). Add dichloromethane (30 mL) followed by magnesium sulfate. Filter, and rinse the filter cake with 100 mL 10% ethanol in dichloromethane. Concentrate to provide 5-(4H-1,2,4-triazol-3-yl)pentanoic acid (1.6 g; >100%) as an alcoholic adduct: MS (m/z): 170 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[C@@H:4]([NH2:29])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][CH2:9][NH:10][C:11](=[O:27])[CH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(N(CC)CC)C.[C:38]1([S:44](Cl)(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>ClCCl>[CH3:1][O:2][C:3](=[O:30])[C@@H:4]([NH:29][S:44]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)(=[O:46])=[O:45])[CH2:5][NH:6][C:7](=[O:28])[CH2:8][CH2:9][NH:10][C:11](=[O:27])[CH2:12][CH2:13][CH:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:18][CH2:19]1
Reactant: COC(=O)[C@@H](N)CNC(=O)CCNC(=O)CCC1CCN(C(=O)OC(C)(C)C)CC1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](CNC(=O)CCNC(=O)CCC1CCN(C(=O)OC(C)(C)C)CC1)NS(=O)(=O)c1ccccc1
Reaction time: 0.5 h

Procedure:
The compound (120 mg) obtained in the above (5) is dissolved in dichloromethane (3 ml), and thereto are added triethylamine (98 μl) and benzenesulfonyl chloride (54 μl) at room temperature, and the mixture is stirred for 30 minutes. Triethylamine (98 μl) and benzenesulfonyl chloride (81 μl) are further added, and the mixture is stirred for 90 minutes. The mixture is evaporated under reduced pressure to remove the solvent, and to the residue is added ethyl acetate. The mixture is washed successively with 1N hydrochloric acid (twice), a saturated brine (once), a saturated aqueous sodium hydrogen carbonate solution (twice) and a saturated brine (twice), and dried over anhydrous magnesium sulfate. The desiccant is removed by filtration, and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography (silica gel; 20 g, solvent; chloroform-methanol=30:1 to 10:1). The fractions containing the title compound are concentrated under reduced pressure to give the title compound (151 mg).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[CH2:10][CH:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[C:8]2[CH:22]=[CH:23][CH:24]=[CH:25][C:7]=2[CH2:6][CH2:5]1.C(N(CC)CC)C.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35]>C(Cl)(Cl)Cl>[CH2:37]([O:36][C:34]([NH:1][CH2:2][CH2:3][N:4]1[CH2:10][CH:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:14][CH:13]=2)[C:8]2[CH:22]=[CH:23][CH:24]=[CH:25][C:7]=2[CH2:6][CH2:5]1)=[O:35])[CH3:38]
Reactant: NCCN1CCc2ccccc2C(Oc2ccc(C(F)(F)F)cc2)C1
Reactant: CCOC(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCOC(=O)NCCN1CCc2ccccc2C(Oc2ccc(C(F)(F)F)cc2)C1
Temperature: 25 °C

Procedure:
To a cooled solution of 3-(2-aminoethyl)-2,3,4,5-tetrahydro-1-(p-trifluoromethylphenoxy)-3-benzazepine of Example 19b (5.5 g, 0.016 mole) and triethylamine (1.8g, 0.018 mole) in chloroform (75 ml) was slowly dropped a solution of ethyl chloroformate (2.0 g, 0.018 mole) in chloroform (25 ml). After stirring twenty hours at ambient temperature the reaction mixture was concentrated to a semisolid which was dissolved in ether, washed with water and dried (saturated NaCl, anhydrous MgSO4). The solution was filtered and concentrated to yield an oil. A sample of the resultant oil was distilled to yield an oil of 3-(2-ethoxycarbonylaminoethyl)-2,3,4,5-tetrahydro-1-(p-trifluoromethylphenoxy)-3-benzazepine, bp 235°-238° C./0.10 mm.
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]([C:31]1[CH:36]=[CH:35][N:34]=[CH:33][N:32]=1)[S:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]2[C:23]2[N:27]([CH3:28])[N:26]=[CH:25][CH:24]=2)=[C:12]([F:29])[C:11]=1[F:30])(=[O:9])=[O:8].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[F:30][C:11]1[C:12]([F:29])=[C:13]([O:16][C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]2[C:23]2[N:27]([CH3:28])[N:26]=[CH:25][CH:24]=2)[CH:14]=[CH:15][C:10]=1[S:7]([NH:6][C:31]1[CH:36]=[CH:35][N:34]=[CH:33][N:32]=1)(=[O:8])=[O:9]
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2ccc(O[C@H]3CCCC[C@@H]3c3ccnn3C)c(F)c2F)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1nccc1[C@H]1CCCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)c(F)c1F
Yield: 98.9 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the N-(2,4-dimethoxybenzyl)-2,3-difluoro-4-{[(1S*,2R*)-2-(1-methyl-1H-pyrazol-5-yl)cyclohexyl]oxy}-N-(pyrimidin-4-yl)benzenesulfonamide (0.050 g, 0.09 mmol) prepared in Example 40a, triethylsilane (0.07 mL), trifluoroacetic acid (0.09 mL) and dichloromethane (0.9 mL), to yield the title compound (0.040 g, 86%) as a colorless solid.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:15][C:14](=[CH2:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])(C)(C)C.[O:17]=[C:18]1[C:23](C(Cl)=O)=[CH:22][CH:21]=[C:20]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[O:19]1.[N:32]1[C:41]2[C:36](=[CH:37][C:38]([NH2:42])=[CH:39][CH:40]=2)[CH:35]=[CH:34][CH:33]=1>>[CH2:16]=[C:14]1[CH2:15][N:8]([C:6]([C:23]2[C:18](=[O:17])[O:19][C:20]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:21][CH:22]=2)=[O:7])[C@H:9]([C:10]([NH:42][C:38]2[CH:37]=[C:36]3[C:41](=[CH:40][CH:39]=2)[N:32]=[CH:33][CH:34]=[CH:35]3)=[O:12])[CH2:13]1
Reactant: Nc1ccc2ncccc2c1
Reactant: CCCCCc1ccc(C(=O)Cl)c(=O)o1
Reactant: C=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Product: C=C1C[C@@H](C(=O)Nc2ccc3ncccc3c2)N(C(=O)c2ccc(CCCCC)oc2=O)C1

Procedure:
Following the general method as outlined in Example 22, starting from 1-(tert-butoxycarbonyl)-4-methyleneproline, 2-oxo-6-pentyl-2H-pyran-3-carbonyl chloride, and 6-quinolinamine the title compound was obtained in 48% purity by LC/MS. (ESI+): m/z=446.2.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:16]([O-:20])(=[O:19])[CH:17]=C.[CH2:21](O)C>[Pd]>[CH2:14]([N:11]([CH2:12][CH3:13])[S:8]([C:5]1[CH:6]=[CH:7][C:2]([CH2:1][CH2:17][C:16]([O:20][CH3:21])=[O:19])=[CH:3][CH:4]=1)(=[O:10])=[O:9])[CH3:15]
Reactant: CCN(CC)S(=O)(=O)c1ccc(C)cc1
Reactant: CCO
Reactant: C=CC(=O)[O-]
Agent: [Pd]
Product: CCN(CC)S(=O)(=O)c1ccc(CCC(=O)OC)cc1

Procedure:
To 14.5 g of N,N-diethyl-4-bromobenzenesulfonamide (50 mmol) (prepared by reaction of 4-bromobenzenesulfonyl chloride with diethylamine) was added 13.8 g of tetrabutylammonium chloride (50 mmol), 10.3 g of NaHCO3 (124 mmol), 266 mg of palladium (II) acetate (1.07 mmol) and 100 mL of DMF in the order given. To this suspension was added 8.8 ml of methyl acrylate (98 mmol) and the reaction was stirred 1 hour at 80°. The reaction was cooled, 500 mL of water and 900 mL of ether were added, the layers were separated and the ether layer was filtered to remove Pd (0) and combined with 2 further ether washes of the aqueous phase. The combined ether solutions were dried over MgSO4, filtered, stripped and recrystallized from methanol/ether to yield 9.4 g of methyl 4-(diethylaminosulfonyl) benzene-2-propenoate. Six grams of the propenoate was reduced in ethanol at 3.5 atm over 10% Pd on carbon in a Parr Shaker to produce 5.9 g of product as a yellow oil. It was used in that form in Example 269.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].Cl.[CH3:9][NH:10][O:11][CH3:12]>C(N(CC)CC)C>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([N:10]([O:11][CH3:12])[CH3:9])=[O:6]
Reactant: CNOC
Reactant: O=C(Cl)CCCCl
Agent: Cl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)CCCCl
Reaction time: 1.5 h
Yield: 89.4 %

Procedure:
To a solution of 4-chlorobutyryl chloride (10.0 g in 200 mL of dry methylene chloride) was added 10.4 g of N,O-dimethylhydroxylamine hydrochloride. The mixture was stirred under nitrogen and maintained below 25° C. by cooling in an ice bath as necessary while triethylamine (29.1 mL)was added dropwise over about 20 minutes, resulting in precipitation. After 1.5 hours at room temperature, the mixture was concentrated in vacuo. The residue was partitioned between 100 mL of diethyl ether and 100 mL of saturated aqueous sodium bicarbonate solution. The organic layer was washed with an additional 100 mL of saturated sodium bicarbonate, and the aqueous fractions were back-extracted with ether. The combined organic phases were dried over sodium sulfate, filtered, and concentrated in vacuo to give 10.5 g (90%) of an oil, which had satisfactory purity by 1H NMR (CDCl3). Mass spectrum (PB--NH3 /Cl): m/e=166 (M+H).
Reaction SMILES: C(OC([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=1[CH2:17][C:18](=O)[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=O)(C)(C)C.FC(F)(F)C(O)=O.[BH4-].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(O)C>[CH2:19]([CH:18]1[CH2:17][C:11]2[C:10](=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:16])[CH2:9][NH:8]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)(C)OC(=O)NCc1cccc(Cl)c1CC(=O)Cc1ccccc1
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCO
Product: Clc1cccc2c1CC(Cc1ccccc1)NC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 58.8 %

Procedure:
427 mg of 1-[2-(tert-butoxycarbonylaminomethyl)-6-chlorophenyl]-3-phenyl-2-propanone was dissolved in 5 mL of methylene chloride, and 3 mL of trifluoroacetic acid was added thereto under ice-cooling, followed by stirring at room temperature for 1 hour. After confirming the loss of the starting material, it was concentrated under reduced pressure, and the residue obtained was dissolved in 5 mL of ethanol. 173 mg of sodium borohydride was added thereto under ice-cooling, followed by stirring at room temperature for 1 hour. After completion of the reaction, a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue obtained was recrystallized using chloroform hexane to obtain 173 mg of a title compound as a white crystal. Further, a mother liquor upon recrystallization operation was purified using PLC (chloroform:methanol=20:1) to obtain 88.6 mg of a title compound as a pale yellow oily substance. In total, 262 mg (yield 89%) of a title compound was obtained.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH:7]([NH2:10])([CH3:9])[CH3:8].[C:11]([Si:15]([O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]I)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:14])([CH3:13])[CH3:12].O>C1COCC1>[Si:15]([O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][NH:10][CH:7]([CH3:9])[CH3:8])([C:11]([CH3:12])([CH3:13])[CH3:14])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(C)(C)[Si](OCCCCCI)(c1ccccc1)c1ccccc1
Reactant: CC(C)N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)NCCCCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reaction time: 12 h
Yield: 84.9 %

Procedure:
K2CO3 (1.50 g, 11.05 mmol), isopropylamine (0.65 mL, 11.05 mmol) and iodide 3 (2.50 g, 5.83 mmol) in dry THF (15 mL) were heated at 66° C. in a sealed tube under an argon atmosphere. After 12 h, water (5 mL) was added to the reaction mixture which was then extracted with EtOAc (3×50 mL). The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure to afford 4 as a colorless liquid (1.90 g, 92%) sufficiently pure it was used without further purification. TLC: MeOH/CH2Cl2 (1:4), Rf˜0.30; 1H NMR (400 MHz) δ 7.65-7.67 (m, 4H), 7.30-7.40 (m, 6H), 3.65 (t, J=6.4 Hz, 2H), 2.70-2.82 (m, 1H), 2.55 (t, J=7.3 Hz, 2H), 1.50-1.64 (m, 2H), 1.32-1.50 (m, 4H), 1.05 (d, J=5.8 Hz, 3H), 1.04 (s, 9H); 13C NMR (100 MHz) δ 135.68, 134.21, 129.63, 127.70, 63.95, 48.81, 47.64, 32.60, 30.27, 27.0, 23.76, 23.15, 19.34.
Reaction SMILES: N1C=CC=CC=1.N([C@@H:10]1[C@@H:14]([CH2:15][OH:16])[O:13][C@@H:12]([N:17]2[CH:25]=[C:23]([CH3:24])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[CH2:11]1)=[N+]=[N-].[C:26](OC(=O)C)(=[O:28])[CH3:27]>C(Cl)(Cl)Cl>[C:26]([O:16][CH2:15][C@H:14]1[O:13][C@@H:12]([N:17]2[CH:25]=[C:23]([CH3:24])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[CH2:11][CH2:10]1)(=[O:28])[CH3:27]
Reactant: Cc1cn([C@H]2C[C@H](N=[N+]=[N-])[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: CC(=O)OC[C@@H]1CC[C@H](n2cc(C)c(=O)[nH]c2=O)O1
Reaction time: 8 h

Procedure:
To a pyridine (50 ml) solution of 3'-azido-3'-deoxythymidine (5.0 g, 18.7 mmole) 1 was added acetic anhydride dropwise in an ice-water bath. The mixture was allowed to stand overnight in the refrigerator. The solution was then poured into CHCl3 (20 ml), washed with H2O (200 ml×2), with a saturated solution of sodium bicarbonate and then H2O (200 ml×2). The organic layer was then dried (MgSO4). After removing the solvent, a syrup (6.5 g) was obtained.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=2)[CH2:10]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Br)(Br)[Br:16]>CCCCCC>[C:1]1([C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=2)[CH2:10][Br:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCc1cccc(-c2ccccc2)c1
Reactant: BrP(Br)Br
Solvent: CCCCCC
Product: BrCc1cccc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 198.5 %

Procedure:
To a solution of 5.57 g (30 mmol) of 3-phenylbenzylalcohol in n-hexane was added dropwise 4.06 g (13.5 mmol) of phosphorous tribromide with ice-cooling. The mixture was removed from an ice bath and stirred at room temperature for 3.5 hours. To the reaction mixture were added ice water and tert-butyl methyl ether and the mixture was stirred for 30 minutes and separated. The organic layer was washed twice with water, dried and concentrated to obtain 6.62 g (26.8 mmol) of 3-phenylbenzylbromide.
Reaction SMILES: C([Si]([O:8]/[C:9](/[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)=[CH:10]\[CH3:11])(C)C)(C)(C)C.CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:41]C)C=C4)N(CC2)C1.CS(N)(=O)=O.C(Cl)(Cl)Cl>C(O)(C)(C)C.O>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([C:9](=[O:8])[C@H:10]([OH:41])[CH3:11])[CH:17]=[CH:16][CH:15]=1
Reactant: CC[C@H]1CN2CC[C@H]1C[C@@H]2[C@@H](Oc1nnc(O[C@@H](c2ccnc3ccc(OC)cc23)[C@H]2C[C@@H]3CCN2C[C@@H]3CC)c2ccccc12)c1ccnc2ccc(OC)cc12
Reactant: C/C=C(\O[Si](C)(C)C(C)(C)C)c1cccc(OC)c1
Agent: CS(N)(=O)=O
Solvent: CC(C)(C)O
Solvent: O
Solvent: ClC(Cl)Cl
Product: COc1cccc(C(=O)[C@@H](C)O)c1

Procedure:
Compound 10f was synthesized by a procedure similar to that described for (R)-10a using (Z)-tert-butyl(1-(3-methoxyphenyl)prop-1-enyloxy)dimethylsilane, (9f, 8.1 g, 0.029 mol), AD-mix-β (40.7 g), and CH3SO2NH2 (2.8 g, 0.0294 mol) in tert-butyl alcohol-water (110 mL:110 mL) The reaction was quenched with sodium sulfite (29.1 g). After purification, 4.2 g (80%) of the desired 10f was isolated: [α]20D +71.1° (c 1.1, CHCl3); 1H NMR (CDCl3) δ 7.51-7.45 (m, 2H), 7.44-7.37 (m, 1H), 7.19-7.13 (m, 1H), 5.19-5.09 (m, 1H), 3.87 (s, 3H), 3.76 (d, 1H, J=6.5 Hz), 1.45 (d, 3H, J=7.1 Hz); 13C NMR (CDCl3) δ 202.3, 160.0, 134.7, 129.9, 121.1, 120.3, 113.1, 69.4, 55.5, 22.4. C10H12O3.