Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NCC1SC(C2C=[C:12]3[C:16](=[C:17](C(N)=O)C=2)[NH:15]C=C3C2CCN(S(CC)(=O)=O)CC2)=CC=1)C.[CH:33]([C:35]1[S:39][C:38]([B:40]([OH:42])[OH:41])=[CH:37][CH:36]=1)=O.C(N)(C)C.[BH3-]C#N.[Na+]>>[CH3:12][CH:16]([NH:15][CH2:33][C:35]1[S:39][C:38]([B:40]([OH:42])[OH:41])=[CH:37][CH:36]=1)[CH3:17]
Reactant: O=Cc1ccc(B(O)O)s1
Reactant: CCNCc1ccc(-c2cc(C(N)=O)c3[nH]cc(C4CCN(S(=O)(=O)CC)CC4)c3c2)s1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(C)N
Product: CC(C)NCc1ccc(B(O)O)s1

Procedure:
Following the general procedure of 5-{5-[(ethylamino)methyl]-2-thienyl}-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, (5-formyl-2-thienyl)boronic acid (50 mg, 0.32 mmol), isopropylamine (0.027 mL, 0.32 mmol), and NaCNBH3 (40 mg, 0.64 mmol) were reacted to give 41 mg of crude (5-{[(1-methylethyl)amino]methyl}-2-thienyl)boronic acid. The crude (5-{[(1-methylethyl)amino]methyl}-2-thienyl)boronic acid was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (80 mg, 0.193 mmol), potassium carbonate (160 mg, 1.16 mmol), and tetrakis(triphenylphosphine)palladium(0) (5 mg, 0.004 mmol) to give 74 mg of the title compound (37%).
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:39])[N:9]2[CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([N:20]([CH2:28][C:29]3[N:34]=[CH:33][C:32]4[O:35][CH2:36][CH2:37][O:38][C:31]=4[CH:30]=3)[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]2)=[N:4][CH:3]=1.[C:40](=[O:47])([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[NH2:41].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[C:43]([O:42][C:40]([NH:41][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:39])[N:9]2[CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([N:20]([CH2:28][C:29]3[N:34]=[CH:33][C:32]4[O:35][CH2:36][CH2:37][O:38][C:31]=4[CH:30]=3)[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]2)=[N:4][CH:3]=1)=[O:47])([CH3:46])([CH3:45])[CH3:44]
Reactant: CC(C)(C)OC(N)=O
Reactant: CC(C)(C)OC(=O)N(Cc1cc2c(cn1)OCCO2)C1CCN(CCn2c(=O)ccc3ncc(Br)cc32)CC1
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)Nc1cnc2ccc(=O)n(CCN3CCC(N(Cc4cc5c(cn4)OCCO5)C(=O)OC(C)(C)C)CC3)c2c1
Temperature: 90 °C
Reaction time: 38 h
Yield: 75.4 %

Procedure:
To a solution of 0.85 g of tert-butyl (1-(2-(7-bromo-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)carbamate in 5 mL of 1,4-dioxane, 0.20 g of tert-butyl carbamate, 0.69 g of cesium carbonate and 13 mg of tris(benzylideneacetone)dipalladium and 24 mg of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene were added, and the mixture was stirred at 90° C. for 38 hours under a nitrogen atmosphere. After cooling to room temperature, the insoluble substance was separated by filtration, and the filtrated solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using silica gel; Silica Gel 60 made by KANTO CHEMICAL CO., INC., and an eluent of hexane:ethyl acetate=33:67 to 5:95 to obtain 0.68 g of tert-butyl (1-(2-(7-((tert-butoxycarbonyl)amino)-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)carbamate as a white solid.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>>[F:17][C:4]1[CH:3]=[C:2]([C:22]2[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=2)[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=1
Reactant: Cc1c2n(c3c(Br)cc(F)cc13)CCNC2=O
Reactant: OB(O)c1ccc(F)cc1
Product: Cc1c2n(c3c(-c4ccc(F)cc4)cc(F)cc13)CCNC2=O

Procedure:
The title compound, light grey solid (64 mg, 82%), MS (ISP) m/z=313.4 [(M+H)+], mp 182° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-fluoro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 14) (74.3 mg, 0.25 mmol) and commercially available 4-fluoro-phenylboronic acid (45.5 mg, 0.325 mmol).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:34])[CH2:10][CH2:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][C@@H:16]1[C@@H:20](/[CH:21]=[CH:22]/[C@@H:23]([OH:31])[CH:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28][Cl:29])[C@H:19]([OH:32])[CH2:18][C@@H:17]1[OH:33].[I:35]I>C(Cl)Cl.C(OCC)C>[CH3:7][O:8][C:9](=[O:34])[CH2:10][CH2:11][CH2:12][CH:13]([I:35])[CH:14]1[O:33][C@H:17]2[CH2:18][C@@H:19]([OH:32])[C@H:20](/[CH:21]=[CH:22]/[C@@H:23]([OH:31])[CH:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28][Cl:29])[C@H:16]2[CH2:15]1
Reactant: II
Reactant: COC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](O)C(C)CCCCCl)[C@H](O)C[C@@H]1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: ClCCl
Product: COC(=O)CCCC(I)C1C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CCCCCl)[C@H](O)C[C@@H]2O1
Temperature: 0 °C
Yield: 74.1 %

Procedure:
Under an atmosphere of nitrogen, 194 mg of anhydrous potassium carbonate was added to a solution of 140 mg of (5Z,13E)-(9α,11α,15S,16RS)-9,11,15-trihydroxy-16-methyl-20-chloroprosta-5,13-dienoic acid methyl ester [prepared as described in Example 8 of British Patent Application No. 22090/75 and e.g. the equivalent Belgian Specification No. 842,113] in 5 ml of methylene chloride. To the reaction mixture was added 200 mg of iodine in portions during 2 hours with stirring at 0° C. The reaction mixture was diluted with diethyl ether, washed with an aqueous solution of sodium thiosulphate, water and an aqueous solution of sodium chloride, dried over anhydrous magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate (2:1) as eluent to give 135 mg of the title compound having the following physical characteristics:
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH:16]=O)=[CH:14][N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:25][O:26][C:27](=[O:30])[CH2:28][NH2:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:25][O:26][C:27](=[O:30])[CH2:28][NH:29][CH2:16][C:13]1[S:12][C:11]([NH:10][C:8]([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:9])=[N:15][CH:14]=1
Reactant: O=Cc1cnc(NC(=O)N(C2CCCCC2)C2CCCCC2)s1
Reactant: COC(=O)CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Product: COC(=O)CNCc1cnc(NC(=O)N(C2CCCCC2)C2CCCCC2)s1
Yield: 38.6 %

Procedure:
Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (31 mg, 0.095 mmol), glycine methyl ester hydrochloride (24 mg, 0.20 mmol) and sodium triacetoxyborohydride (61 mg, 0.286 mmol) to afford 15 mg (39%) of the desired product after purification.
Reaction SMILES: [N:1]1([CH2:7][CH:8]2[N:13](N)[C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[O:10][CH2:9]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27](=[O:31])[CH2:28][CH:29]=O)=[CH:23][CH:22]=1.O=CCC=O.CC(C1C=CC(OC)=CC=1)=O.C(OC)=O.[H-].[Na+]>C(O)(=O)C.C(OCC)C.C(O)C.C(OCC)(=O)C>[N:1]1([CH2:7][CH:8]2[N:13]3[CH:29]=[C:28]([C:27](=[O:31])[C:24]4[CH:25]=[CH:26][C:21]([O:20][CH3:19])=[CH:22][CH:23]=4)[C:15]4[CH:16]=[CH:17][CH:18]=[C:11]([C:12]=43)[O:10][CH2:9]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: NN1c2ccccc2OCC1CN1CCOCC1
Reactant: COc1ccc(C(=O)CC=O)cc1
Agent: COc1ccc(C(C)=O)cc1
Agent: O=CCC=O
Agent: [H-]
Solvent: CCOCC
Solvent: COC=O
Solvent: CCOC(C)=O
Product: COc1ccc(C(=O)c2cn3c4c(cccc24)OCC3CN2CCOCC2)cc1

Procedure:
3-(4-morpholinylmethyl)-6-(4-methoxybenzoyl)-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine, m.p. 209°-214° C. (1.5 g from ethyl acetate) was prepared by reaction of 13 g (0.052 mole) of 3-(4-morpholinylmethyl)-4-amino-3,4-dihydro-2H-1,4-benzoxazine with 10.2 g (0.057 mole) β-(4-methoxyphenyl)-β -ketopropionaldehyde in glacial acetic acid (the β-ketopropionaldehyde being prepared by reaction of 4-methoxyacetophenone with methyl formate in diethyl ether in the presence of ethanol and sodium hydride).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:20])=[C:11]([CH2:13][CH2:14]OS(C)(=O)=O)[N:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].CC1C=CC(S(O)(=O)=O)=CC=1.[F:40][CH2:41][C@@H:42]1[CH2:46][CH2:45][NH:44][CH2:43]1>C(#N)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:20])=[C:11]([CH2:13][CH2:14][N:44]3[CH2:45][CH2:46][C@@H:42]([CH2:41][F:40])[CH2:43]3)[N:12]=2)=[CH:4][CH:3]=1
Reactant: Cc1oc(-c2ccc(Br)cc2)nc1CCOS(C)(=O)=O
Reactant: FC[C@@H]1CCNC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC#N
Product: Cc1oc(-c2ccc(Br)cc2)nc1CCN1CC[C@@H](CF)C1
Yield: 93.5 %

Procedure:
Prepare using the method of Example 102 with 2-[2-(4-bromophenyl)-5-methyl-1,3-oxazol-4-yl]ethyl methanesulfonate (See Intermediate 13) (0.36 g, 0.99 mmole), anhydrous acetonitrile (2 mL), potassium carbonate (0.55 g, 3.98 mmol), potassium iodide (0.016 g, 0.10 mmol) and (3R)-3-(fluoromethyl)pyrrolidine 4-methylbenzenesulfonate (salt) (See Intermediate 57) (0.41 g, 1.49 mmol) to give the title compound as a pale orange oil (0.34 g): MS (m/e) (79Br/81Br): 367, 369(M+1)
Reaction SMILES: [C:1]1([CH:7]=[CH:8][C:9]2[NH:10][CH2:11][CH2:12][N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S:14](Br)(Br)=O>>[S:14]1[C:8]([C:9]2[NH:13][CH2:12][CH2:11][N:10]=2)=[CH:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][C:6]1=2
Reactant: O=S(Br)Br
Reactant: C(=Cc1ccccc1)C1=NCCN1
Product: c1ccc2sc(C3=NCCN3)cc2c1

Procedure:
The title compound was prepared in the essentially the same manner, from 0.34 g (2 mmol) of 2-(2-phenylethen-1-yl)-4,5-dihydro-1H-imidazole and thionyl bromide, as described in Example 31.
Reaction SMILES: [C:1]([Si:5]([CH3:8])([CH3:7])Cl)([CH3:4])([CH3:3])[CH3:2].[I:9][CH2:10][C@H:11]1[NH:14][C:13](=[O:15])[CH2:12]1.C(N(CC)CC)C>CN(C)C=O>[Si:5]([N:14]1[C@H:11]([CH2:10][I:9])[CH2:12][C:13]1=[O:15])([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:8])[CH3:7]
Reactant: O=C1C[C@@H](CI)N1
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)N1C(=O)C[C@H]1CI
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.9 %

Procedure:
t-butyldimethylchlorosilane (7.51 g, 49.8 mmol) is added in one portion to an ice-cold, stirring solution of (4S)-4-iodomethyl-azetidin-2-one (10.0 g, 47.4 mmol) and triethylamine (5.04 g, 49.8 mmol) in anhydrous dimethylformamide (100 ml). A voluminous white precipitate forms almost immediately. The reaction mixture is stirred at 0°-5° for 1 hour and then allowed to warm to room temperature. Most of the solvent is removed under vacuum to give a residue which is partitioned between diethyl ether (250 ml) and water. The ethereal phase is washed with 2.5 N hydrochloride acid (50 ml), water (3×50 ml), and brine, dried with magnesium sulfate, filtered, and evaporated under vacuum to provide (4S)-1-(t-butyldimethylsilyl)-4-iodomethyl-azetidin-2-one (15.1 g) as a white solid. Recrystallization from petroleum ether-ethyl ether gives the product as colorless plates, mp 71°-72°; n.m.r. (CDCl3), δ3.8 (m,1), δ2.6-3.6 (2 overlapping d of AB, 4) δ1.0 (S,9), δ0.3 (S,6), δ0.25 (S,6).
Reaction SMILES: [C:1]([O:4][C:5](=O)[CH3:6])(=O)[CH3:2]>C1COCC1>[CH3:2][CH2:1][CH2:2][CH2:1][O:4][C@H:5]([CH2:6][OH:4])[CH2:5][CH3:6]
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Product: CCCCO[C@@H](CC)CO
Temperature: 5 °C
Reaction time: 8 h

Procedure:
To a 500 ml flask was added 200 g of THF and 8.8 g of 70 wt. % HClO4 aqueous solution. The solution was cooled to 5° C., titrated with 48.0 g of acetic anhydride over 30 minutes, and then stirred for 8 hours, while maintaining the temperature at 5° C. The reaction is then quenched with 190.5 g of 17 wt. % aqueous solution of sodium hydroxide with stirring, the flask is settled and the water layer is removed. 47.1 g of 30 wt. % aqueous solution of sodium hydroxide is added to the oil layer, which is then heated to 120° C. so as to distill off the unreacted monomer, then 140 g of n-butanol, reflux for 3 hours and saponificate the contents. After settling, the water layer is removed, and 94.0 g of water is added to the oil layer. The contents are refluxed with constant stirring for 15 minutes. The contents in the flask are allowed to settle and cooling. The water layer is removed and the oil layer is rinsed with a water. Further, the oil layer is repeatedly rinsed 3 times by water adjusted to pH 2 to 3 by hydrochloric acid, by water adjusted to a pH 3 to 4 and by non treated water and then the water layer is removed. The oil layer is thereafter dried by a vacuum pump (10-20mm Hg pressure) with heating to 120° C. to obtain PTMG. The obtained polymer is transferred to the 100 ml standard bottle and the color number (JIS K-1557, testing method for polyether for polyurethane) is measured.
Reaction SMILES: [CH2:1]([C:4]1[C:13]([OH:14])=[C:12]([N+:15]([O-:17])=[O:16])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])[CH:2]=C.[OH:18]OS([O-])=O.[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.CO>[OH:18][CH:2]1[CH2:1][C:4]2=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:12]([N+:15]([O-:17])=[O:16])=[C:13]2[O:14]1
Reactant: C=CCc1c(C(=O)OC)ccc([N+](=O)[O-])c1O
Reactant: O=S([O-])OO
Agent: [K+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: ClCCl
Product: COC(=O)c1ccc([N+](=O)[O-])c2c1CC(O)O2
Temperature: -78 °C
Reaction time: 0.83 h
Yield: 96 %

Procedure:
Methyl 2-allyl-3-hydroxy-4-nitro-benzoate 1d (5.39 g, 22.70 mmol) was dissolved in 110 mL of the mixture solvent of dichloromethane and methanol (V/V=10:1), the reaction solution was cooled down to −78° C. and filled with oxone. After stirring for 50 minutes, oxone was removed from filling with. The reaction mixture was stirred for another 20 minutes, then filled with argon and stirred for 10 minutes. Triphenyl phosphine (17.80 g, 68.10 mmol) was added. After removing the dry ice bath, the resulting mixture was allowed to room temperature and stirred for 3 hours. The reaction solution was concentrated under reduced pressure, added with 200 mL of ethyl acetate, washed with water (100 mL×3) and saturated sodium chloride solution (100 mL×3) successively, then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound methyl 2-hydroxy-7-nitro-2,3-dihydrobenzofuran-4-carboxylate 1e (5.20 g, yield: 96.0%) as a brown solid.
Reaction SMILES: [C:1]1([C:11]2[CH2:15][CH2:14][C:13](=[O:16])[CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Cl-].[Cl-].[Cl-].[Ce+3].[BH4-].[Na+]>C(O)C>[C:1]1([C:11]2[CH2:15][CH2:14][CH:13]([OH:16])[CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C1C=C(c2cccc3ccccc23)CC1
Agent: [BH4-]
Agent: [Ce+3]
Agent: [Cl-]
Solvent: CCO
Product: OC1C=C(c2cccc3ccccc23)CC1
Reaction time: 0.5 h
Yield: 73.4 %

Procedure:
To a stirred solution of 3-napthalen-1-yl-cyclopent-2-enone (3.36 g, 16.13 mmol) in ethanol (150 mL) was added cerium trichloride (3.98 g, 16.13 mmol) followed portion-wise by sodium borohydride (0.73 g, 19.36 mmol, 1.2 eq.) at room temperature. The reaction mixture was stirred for 0.5 h, until the reaction was shown to be complete by TLC. The reaction was quenched by the addition of saturated aqueous ammonium chloride (100 mL) and the organics were removed in vacuo. The remaining aqueous layer was further diluted with water (100 mL) and extracted with dichloromethane (3×200 mL). The organic extracts were combined, dried over magnesium sulphate and concentrated in vacuo. The crude oil was purified by flash chromatography (SiO2, ethyl acetate:petroleum ether 40-60; 20%:80%) to afford the desired compound as a yellow oil (2.49 g, 74%). 1H NMR (400 MHz, CDCl3) δ ppm 2.01-2.04 (1H, m, CH), 2.44-2.45 (1H, m, CH), 2.77-2.78 (1H, m, CH), 2.93-2.95 (1H, m, CH), 3.60 (1H, q, J 1.3 Hz, CH), 6.07 (1H, q, J 1.3 Hz, CH), 7.24-7.35 (4H, m, ArH), 7.75 (1H, d, J 8.0 Hz, ArH), 7.78 (1H, d, J 8.0 Hz, ArH), 8.15 (1H, d, J 8.0 Hz, ArH).
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([OH:33])[CH2:21][N:22]([CH:30]([CH3:32])[CH3:31])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:16][CH:15]=1.[CH3:34][C@H:35]1[C:43]2[C:42]([C:44]3[CH:49]=[CH:48][C:47](O)=[CH:46][CH:45]=3)=[N:41][CH:40]=[N:39][C:38]=2[CH2:37][CH2:36]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]([O:33][C:47]2[CH:48]=[CH:49][C:44]([C:42]3[C:43]4[CH:35]([CH3:34])[CH2:36][CH2:37][C:38]=4[N:39]=[CH:40][N:41]=3)=[CH:45][CH:46]=2)[CH2:21][N:22]([CH:30]([CH3:31])[CH3:32])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[CH:16][CH:15]=1
Reactant: C[C@@H]1CCc2ncnc(-c3ccc(O)cc3)c21
Reactant: CC(C)N(CC(O)c1ccc(Cl)cc1)C(=O)OC(C)(C)C
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: CC1CCc2ncnc(-c3ccc(O[C@@H](CN(C(=O)OC(C)(C)C)C(C)C)c4ccc(Cl)cc4)cc3)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 7.1 %

Procedure:
Diethyl azodicarboxylate (0.166 mL, 1.05 mmol) was added slowly to a solution of tert-butyl 2-(4-chlorophenyl)-2-hydroxyethyl(isopropyl)carbamate (265 mg, 0.843 mmol), (R)-4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenol (159 mg, 0.703 mmol), and triphenylphosphine (276 mg, 1.05 mmol) in tetrahydrofuran (7.0 mL) at −30° C. (bath). The mixture was allowed to warm up to room temperature and stirred overnight. Most of the starting material remained. Triphenylphosphine (276 mg, 1.05 mmol) was added. The contents were cooled at −30° C. Diethyl azodicarboxylate (0.166 mL, 1.05 mmol) was added. The mixture was stirred at room temperature for 4 hours. tert-Butyl 2-(4-chlorophenyl)-2-hydroxyethyl(isopropyl)carbamate (265 mg, 0.843 mmol) was added. The mixture was stirred at room temperature overnight. EtOAC (10 mL) and water (10 mL) were added. The organic layer was separated. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic solutions were dried (Na2SO4). The crude was purified by flash chromatography to give (R)-tert-butyl 2-(4-chlorophenyl)-2-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenoxy)ethyl(isopropyl)carbamate (26 mg, 7%).
Reaction SMILES: [CH3:1][C:2]([CH3:26])([CH3:25])[C:3]([O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:22]([OH:24])=O)[C:10]([C:13]2[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=2[F:21])=[CH:11][CH:12]=1)=[O:4].S(Cl)(Cl)=O.[CH:31]([NH2:34])([CH3:33])[CH3:32]>C(Cl)Cl.CN(C=O)C>[CH3:25][C:2]([CH3:1])([CH3:26])[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=2[F:21])=[C:9]([C:22]([NH:34][CH:31]([CH3:33])[CH3:32])=[O:24])[CH:8]=1)=[O:4]
Reactant: CC(C)N
Reactant: COc1ccc(F)c(-c2ccc(COC(=O)C(C)(C)C)cc2C(=O)O)c1
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1ccc(F)c(-c2ccc(COC(=O)C(C)(C)C)cc2C(=O)NC(C)C)c1
Temperature: 25 °C
Yield: 78.5 %

Procedure:
To a room temperature solution of 29.2 (432 mg, 1199 μmol) in DCM (6.0 mL) was added two drops of DMF followed by thionyl chloride (0.26 mL, 3596 μmol). The mixture was refluxed under N2 for 1.5 hours, cooled to room temperature, and the organic solvent was removed under reduced pressure. The residue was treated with neat isopropylamine (2.0 mL, 23515 μmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA), and the mixture was heated at 50° C. for 45 minutes. The reaction was then quenched with water (5 mL) and extracted with (3×5 mL) EtOAc. After removal of organic solvents under reduced pressure, purification of the residue by flash chromatography on silica gel with 0-50% EtOAc/hexanes for elution gave 29.3 as white solid (378 mg, 79%).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:7]=[N:8][N:9]([CH3:12])[C:10]=1[OH:11])=[O:5].C(N(CC)CC)C.C1C=CC=CC=1.[N+:31]([C:34]1[CH:41]=[CH:40][C:37]([CH2:38]Cl)=[CH:36][CH:35]=1)([O-:33])=[O:32]>CN(C)C=O>[Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:7]=[N:8][N:9]([CH3:12])[C:10]=1[O:11][CH2:38][C:37]1[CH:40]=[CH:41][C:34]([N+:31]([O-:33])=[O:32])=[CH:35][CH:36]=1)=[O:5]
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Reactant: Cn1ncc(C(=O)c2ccc(Cl)cc2Cl)c1O
Solvent: c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cn1ncc(C(=O)c2ccc(Cl)cc2Cl)c1OCc1ccc([N+](=O)[O-])cc1
Yield: 86.7 %

Procedure:
To a mixture of 1.36 g (0.005 mol) of 4-(2,4-dichlorobenzoyl)-1-methyl-5-hydroxypyrazole, 0.51 g (0.005 mol) of triethylamine, 20 ml of benzene and 10 ml of N,N-dimethylformamide was added with stirring 0.86 g (0.005 mol) of 4-nitrobenzyl chloride at room temperature. The resulting mixture was then heated under reflux for 3 hours. After cooling the reaction mixture, the solvent was distilled off under reduced pressure and 30 ml of water and 30 ml of ethyl acetate were added thereto. After stirring the mixture for a while, an organic layer was separated, washed with water and 5% aqueous sodium bicarbonate and dried. Then the solvent was distilled off therefrom. The resulting oil (2.02 g) was subjected to column chromatography (silica gel, eluting with benzene/ethyl acetate 1:1) to give 1.76 g of the title compound (yield 87%), m.p. 116.5°-117.5° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[H-].[Na+].[CH2:14](Br)[CH:15]=[CH2:16]>CN(C=O)C>[CH2:16]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)[CH:15]=[CH2:14]
Reactant: C=CCBr
Reactant: O=Cc1c[nH]c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCn1cc(C=O)c2ccccc21
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Indole-3-carbaldehyde (1 eq.) was dissolved in DMF (0.46 M). Sodium hydride was added (2.5 eq.) and the resulting solution was stirred at RT for 20 min. Allyl bromide (1 eq.) was then added and the reaction solution was allowed to stir at RT for 20 h. The reaction mixture was subsequently quenched with brine and extracted with EtOAc. The combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a yellow oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→3:7 (v/v) Hex:EtOAc) afforded the title compound as a light yellow oil.