Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].CC(S)(C)C.C[S:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1.Cl>CN(C)C=O>[SH:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1
Reactant: CSc1ccc(C=O)cc1
Agent: Cl
Agent: [Na]
Solvent: CN(C)C=O
Solvent: CC(C)(C)S
Product: O=Cc1ccc(S)cc1
Temperature: 25 °C
Yield: 38.4 %

Procedure:
Combine 2-methyl-2-propanethiol sodium salt (2.9 g, 26.3 mmol) and 4-(methylthio)benzaldehyde (2.0 g, 13.2 mmol) with dimethylformamide (40 mL) in a dry flask then heat at 160° C. for 4 hours. Cooled to room temperature, poured into 3N aqueous hydrochloric acid (400 mL) then extracted with dichloromethane (3×75 mL). The combined dichloromethane extracts were dried over sodium chloride/magnesium sulfate, filtered, and concentrated on a rotary evaporator to yield the crude product (3 g). The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate and hexanes to yield 4-mercapto-benzaldehyde (0.7 g): 1H NMR (DMSO-D6, 300.00 MHz): 9.9 (s, 1H), 7.7 (d, 2H), 7.5 (d, 2H).
Reaction SMILES: C(OC([NH:11][CH2:12][C:13]([NH:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)=[O:14])=O)C1C=CC=CC=1>CO.[Pd]>[NH2:11][CH2:12][C:13]([NH:15][CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:21][CH2:22]1)=[O:14]
Reactant: CC(C)(C)OC(=O)N1CCC(CNC(=O)CNC(=O)OCc2ccccc2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(CNC(=O)CN)CC1
Yield: 91.9 %

Procedure:
A solution of 4-[{(N-(benzyloxycarbonyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (6.26 g, 15.4 mmol) in methanol (100 mL) was hydrogenated at 1 atm in the presence of 5% palladium on charcoal (620 mg) at room temperature for 7 h. The catalyst was removed by filtration through Celite and the combined filtrate was concentrated to afford 4-{(glycylamino)methyl}-1-(tert-butoxycarbonyl)piperidine (3.84 g, 92%) as a solid.
Reaction SMILES: [CH:1]1([CH2:6][N:7]([CH2:26][CH:27]=[CH2:28])[CH:8]([CH3:25])[CH2:9][CH2:10][CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:24]=[CH:23][N:22]=[CH:21]3)=[CH:16][CH:15]=2)=[O:13])[CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Na+]>>[CH:1]1([CH2:6][N:7]([CH2:26][CH:27]=[CH2:28])[CH:8]([CH3:25])[CH2:9][CH2:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:24]=[CH:23][N:22]=[CH:21]3)=[CH:16][CH:15]=2)[OH:13])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C=CCN(CC1CCCC1)C(C)CCCC(=O)c1ccc(-n2ccnc2)cc1
Agent: [BH4-]
Agent: [Na+]
Product: C=CCN(CC1CCCC1)C(C)CCCC(O)c1ccc(-n2ccnc2)cc1

Procedure:
In a manner similar to Example 27, react 5-[(cyclopentylmethyl)(2-propenyl)amino]-1-[4-(1H-imidazol-1-yl)-phenyl]hexan-1-one with sodium borohydride to obtain the title compound.
Reaction SMILES: S(Cl)(Cl)=O.[CH:5]1[C:10]([C@H:11]([NH2:15])[C:12]([OH:14])=[O:13])=[CH:9][CH:8]=[C:7]([F:16])[CH:6]=1.[CH3:17]O>CCOC(C)=O>[NH2:15][C@@H:11]([C:10]1[CH:9]=[CH:8][C:7]([F:16])=[CH:6][CH:5]=1)[C:12]([O:14][CH3:17])=[O:13]
Reactant: N[C@H](C(=O)O)c1ccc(F)cc1
Reactant: CO
Solvent: CCOC(C)=O
Solvent: O=S(Cl)Cl
Product: COC(=O)[C@@H](N)c1ccc(F)cc1
Yield: 100 %

Procedure:
Thionyl chloride (0.475 mL, 6.50 mmol) was added dropwise to a solution of (S)-4-fluorophenylglycine (commercially available from Sigma-Aldrich, Milwaukee, Wis.)(1.00 g, 5.91 mmol) in MeOH (25.0 mL), and the mixture was stirred at reflux for 2 hours. The reaction mixture was then concentrated to afford a brown oil. The residue was dissolved in EtOAc, and the solution was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The aqueous phase was separated and extracted with EtOAc. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford (S)-methyl 2-amino-2-(4-fluorophenyl)acetate (1.1 g, 6.0 mmol, 100% yield) as a brown oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.28 (br. s., 2H), 3.59 (s, 3H), 4.55 (s, 1H), 7.05-7.23 (m, 2H), 7.31-7.53 (m, 2H). m/z (ESI) 184 (M+H)+.
Reaction SMILES: [C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].Cl[C:11]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:12]=1[C:13]([O:15]C(C)(C)C)=[O:14].Cl.[N+](=C)([O-])[O-]>CS(C)=O.O>[C:13]([C:12]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:11]=1[CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])([OH:15])=[O:14]
Reactant: COC(=O)CC(=O)OC
Reactant: CC(C)(C)OC(=O)c1cc([N+](=O)[O-])ccc1Cl
Agent: C=[N+]([O-])[O-]
Agent: Cl
Solvent: O
Solvent: CS(C)=O
Product: COC(=O)C(C(=O)OC)c1ccc([N+](=O)[O-])cc1C(=O)O
Temperature: 75 °C
Reaction time: 4 h
Yield: 87.4 %

Procedure:
Sodium hydride (12.42 g of a 60% dispersion in oil, 310 mmol) was washed with petroleum ether (×3) under nitrogen and suspended in dry DMSO (250 mL). A solution of dimethyl malonate (37.3 mL, 330 mmol) in DMSO (50 mL) was added dropwise over 35 min with water-bath cooling. t-Butyl 2-chloro-5-nitrobenzoate (20.0 g, 78 mmol) was added and the mixture stirred at 70-80° C. under nitrogen for 4 h. The red-brown solution was cooled, poured into water (300 mL), and aq. HCl (2 N, 60 mL) added slowly until the red nitronate colour was dispersed. The mixture was extracted with CH2Cl2 (×3), the extracts were dried (Na2SO4) and evaporated. Formic acid (60 mL) was added to the residue and the mixture stirred at 20° C. for 15 h then 50° C. for 7 h (when tlc analysis showed no remaining t-butyl ester). The formic acid was evaporated and the residue taken up in EtOAc and washed with aq. NaCl (×3). The organic layer was extracted with aq. NaHCO3 (×3), the aqueous phase acidified (c.HCl), and extracted with CH2Cl2 (×3). The organic phase was dried (Na2SO4), evaporated, and the residue recrystallised from benzene (two crops) to give dimethyl (2-carboxy-4-nitrophenyl)malonate as cream needles (20.27 g, 88%), mp 163-164° C. 1H NMR (CDCl3) δ8.99 (d, J=2.5 Hz, 1H, H-3), 8.44 (dd, J=8.6, 2.5 Hz, 1H, H-5), 8.4 (v br s, 1H, CO2H), 7.73 (d, J=8.6 Hz, 1H, H-6), 5.94 (s, 1H, ArCH), 3.83 (s, 6H, CO2Me); 13C NMR δ169.6, 167.8 (CO2Me, CO2H), 147.4, 141.4, 132.2, 129.7, 127.6, 126.8 (C-1,2,3,4,5,6), 54.4 (ArCH), 53.3 (OMe). Anal. Calculated for CH11NO8 : C, 48.5; H, 3.7; N, 4.7. Found: C, 48.7; H, 3.7; N, 5.0%.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([Mg]Br)=[CH:16][CH:15]=1.[BH4-].[Na+].Cl>C1COCC1>[CH3:1][O:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]([C:17]2[CH:18]=[CH:19][C:14]([O:13][CH3:12])=[CH:15][CH:16]=2)[NH2:9])=[CH:6][CH:5]=1
Reactant: COc1ccc([Mg]Br)cc1
Reactant: COCc1ccc(C#N)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCc1ccc(C(N)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To the product of Step A (1.5 g, 10.19 mmol) in THF (15 mL) was added 4-methoxyphenylmagnesium bromide (11.21 mL, 11.21 mmol, 1.0 M). The reaction aged at rt for 3.5 h and was concentrated. The residue was dissolved in MeOH (20 mL) and then slowly treated with NaBH4 (0.386 g, 10.19 mmol). The reaction was stirred at rt overnight, concentrated and treated with aq. HCl (15 mL, 30 mmol, 2.0 M). The aqueous portion was extracted with EtOAc (2×) and the combined organic layers were washed with a 1:1 solution of aq. 2.0 M NaOH/brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel gradient eluted with 0-100% EtOAc/hexane to afford the title compound. HPLC/MS: 241.0 (M—NH2)+; Rt=1.91 min.
Reaction SMILES: [CH3:1][C:2]1[C:8]([OH:9])=[CH:7][CH:6]=[CH:5][C:3]=1[OH:4].[Cl:10]N1C(=O)CCC1=O>CO>[Cl:10][C:7]1[CH:6]=[CH:5][C:3]([OH:4])=[C:2]([CH3:1])[C:8]=1[OH:9]
Reactant: O=C1CCC(=O)N1Cl
Reactant: Cc1c(O)cccc1O
Solvent: CO
Product: Cc1c(O)ccc(Cl)c1O
Reaction time: 6 h
Yield: 64.8 %

Procedure:
To a solution of 2-methylresorcinol (40 g, 322 mmol) in 750 ml of methanol was added (45.17 g, 0.338 mol) of N-chlorosuccinimide. The mixture was stirred for 6 hours. The solvent was evaporated and the resulting solid was triturated in 500 ml of a 2:1 mixture of hexane and ethyl acetate. The brown crystalline precipitate (succinimide) was filtered off and rinsed with a little extra solvent. The filtrate was concentrated to give the crude product, which was further purified on silica eluting with 4:1 hexanes/ethyl acetate. Appropriate fractions were combined, and evaporated. The product was crystallized from about 1:8 ether/hexanes to afford 33.1 g (65%) of the desired substituted resorcinol 15b. 1H NMR (DMSO-d6) δ: 9.38 (s, 1H), 8.83 (s, 1H), 6.92 (d, J=8.5 Hz, 1H), 6.33 (d, J=8.5 Hz, 1H), 2.00 (s, 3H).
Reaction SMILES: C1(SC2C=CC(C(C3C=CC(C)=C(OC)N=3)=O)=CC=2)CC1.[Si]([O:29][CH2:30][C:31]1([CH2:34][S:35]([C:38]2[N:42]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[N:41]=[N:40][N:39]=2)(=[O:37])=[O:36])[CH2:33][CH2:32]1)(C(C)(C)C)(C)C>>[C:43]1([N:42]2[C:38]([S:35]([CH2:34][CH:31]3[CH2:32][CH2:33][O:29][CH2:30]3)(=[O:37])=[O:36])=[N:39][N:40]=[N:41]2)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: CC(C)(C)[Si](C)(C)OCC1(CS(=O)(=O)c2nnnn2-c2ccccc2)CC1
Agent: COc1nc(C(=O)c2ccc(SC3CC3)cc2)ccc1C
Product: O=S(=O)(CC1CCOC1)c1nnnn1-c1ccccc1

Procedure:
The title compound was obtained as a pale yellow solid (3.2 mg, 1% (three steps)) by performing substantially the same reaction as in Examples 1-47(1), 1-2 and 1-1(2) sequentially except for using [4-(cyclopropylsulfanyl)phenyl](6-methoxy-5-methylpyridin-2-yl)methanone obtained in Reference Example 1-37 and using 5-({[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropyl]methyl}sulfonyl)-1-phenyl-1H-tetrazole obtained in Reference Example 3-13 in place of 1-phenyl-5-[(tetrahydrofuran-3-ylmethyl)sulfonyl]-1H-tetrazole.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH:11]2[NH:15][CH:14]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:13]3([C:28]4[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[CH:12]2[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=2[F:38])=[O:10])=[C:4]([O:39][CH3:40])[CH:3]=1.C(N(CC)CC)C.[C:48](Cl)(=[O:50])[CH3:49]>C1COCC1>[C:48]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH:11]2[NH:15][CH:14]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:13]3([C:28]4[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[CH:12]2[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=2[F:38])=[O:10])=[C:4]([O:39][CH3:40])[CH:3]=1)(=[O:50])[CH3:49]
Reactant: COc1cc(N)ccc1NC(=O)C1NC(CC(C)(C)C)C2(C(=O)Nc3cc(Cl)ccc32)C1c1cccc(Cl)c1F
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1cc(NC(C)=O)ccc1NC(=O)C1NC(CC(C)(C)C)C2(C(=O)Nc3cc(Cl)ccc32)C1c1cccc(Cl)c1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-amino-2-methoxy-phenyl)-amide (17 mg, 0.029 mmol) and triethylamine (4 mg, 0.044 mmol) in THF (2 mL) was acetyl chloride (2.3 mg, 0.029 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic layer, was separated, and aqueous layer was extracted with ethyl acetate. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-acetylamino-2-methoxy-phenyl)-amide as a off white solid (17 mg, 93%).
Reaction SMILES: [C:1]([N:20]1[N:24]=[N:23][C:22]([CH2:25][CH2:26][CH2:27][CH2:28][N:29]2C(=O)C3C(=CC=CC=3)C2=O)=[N:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NN>CC(O)C.C1COCC1>[C:1]([N:20]1[N:24]=[N:23][C:22]([CH2:25][CH2:26][CH2:27][CH2:28][NH2:29])=[N:21]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCCc1nnn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: NN
Solvent: CC(C)O
Solvent: C1CCOC1
Product: NCCCCc1nnn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 109.1 %

Procedure:
To a solution of 2-[4-(2-trityl-2H-tetrazol-5-yl)-butyl]-isoindole-1,3-dione (175 mg, 0.313 mmol) in 2-propanol/THF (2:1, 3.0 mL) was added hydrazine (30 mL, 0.939 mmol). The solution was stirred at ambient temperature for 16 h. White solid was filtered off and washed with DCM (5×). The filtrate and the washings were combined, concentrated, dissolved in DCM, washed with H2O (2×) and brine, dried over Na2SO4, and concentrated to give the title compound (131 mg, 97% yield) as a pale yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=4)[CH:12]=[C:11]([C:25]([NH2:27])=[O:26])[C:7]=3[NH:8][C:9]=2[CH:10]=1.[CH3:28][C:29](=O)[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O.N>C(Cl)Cl.C1COCC1.CO.O>[CH:29]([NH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=4)[CH:12]=[C:11]([C:25]([NH2:27])=[O:26])[C:7]=3[NH:8][C:9]=2[CH:10]=1)([CH3:30])[CH3:28]
Reactant: CC(C)=O
Reactant: NC(=O)c1cc(-c2cccc(C(F)(F)F)c2)nc2c1[nH]c1cc(N)ccc12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: N
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)Nc1ccc2c(c1)[nH]c1c(C(N)=O)cc(-c3cccc(C(F)(F)F)c3)nc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 55.6 %

Procedure:
A suspension of 7-amino-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (30 mg, 0.081 mmol), propan-2-one (0.118 mL, 1.62 mmol), and sodium triacetoxyborohydride (172 mg, 0.810 mmol) in a mixture of DCM/THF (2/1) (3 mL) was stirred at RT overnight. The mixture was diluted with MeOH and preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA, 10-60% B at 42 mL/min over 20 min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 7-(isopropylamino)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (20 mg, 0.045 mmol, 55% yield). MS (ESI) m/z 413.20 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.13 (1H, s), 8.58 (2H, s), 8.51 (1H, s), 8.29 (1H, s), 7.90 (1H, d J=8.56 Hz), 7.81 (1H, s), 7.68-7.77 (2H, m), 6.80 (1H, d, J=1.76 Hz), 6.60 (1H, dd, J=8.56, 2.01 Hz), 6.00 (1H, d, J=7.55 Hz), 3.53-3.68 (1H, m), 1.21 (6H, d, J=6.30 Hz).
Reaction SMILES: [ClH:1].[F:2][C:3]([F:36])([F:35])[C:4]1[CH:5]=[C:6]([C@H:14]([N:16]([CH3:34])[C:17]([N:19]2[C@@H:25]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=3[CH3:33])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[O:18])[CH3:15])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.[CH2:37]=O>CO.[Pd]>[ClH:1].[F:36][C:3]([F:2])([F:35])[C:4]1[CH:5]=[C:6]([C@H:14]([N:16]([CH3:34])[C:17]([N:19]2[C@@H:25]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=3[CH3:33])[CH2:24][CH2:23][N:22]([CH3:37])[CH2:21][CH2:20]2)=[O:18])[CH3:15])[CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=1
Reactant: Cc1cc(F)ccc1[C@H]1CCNCCN1C(=O)N(C)[C@H](C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: C=O
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: Cc1cc(F)ccc1[C@H]1CCN(C)CCN1C(=O)N(C)[C@H](C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 1 h

Procedure:
A mixture of example 4 (10 mg), aqueous formaldehyde (29 μL) and 10% Pd/C (5 mg) in anhydrous MeOH (1 mL) was hydrogenated at r.t. and Patm. for 1 hour. The mixture was filtered and the organic layer was concentrated in vacuo. The residue was triturated with Et2O/pentane to give the title compound (5 mg) as a whitish solid.
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([CH3:12])=[CH:7][C:8]=2[CH3:11])[C:3]1=O.Cl.[CH2:15](OCC)C>>[CH3:1][C:2]1[CH2:3][C:4]2[C:9]([C:10]=1[CH3:15])=[C:8]([CH3:11])[CH:7]=[C:6]([CH3:12])[CH:5]=2
Reactant: Cc1cc(C)c2c(c1)C(=O)C(C)C2
Reactant: CCOCC
Agent: Cl
Product: CC1=C(C)c2c(C)cc(C)cc2C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 94.3 %

Procedure:
2,4,6-Trimethylindanone (30.0 g, 0.17 moles) was stirred in diethylether (300 mL) at 0° C. as MeMgl (0.24 moles, 80.00 mL of 3.0 M solution in diethylether) was added dropwise. This mixture was stirred for another 30 minutes at 0° C. and then at 20° C. for an additional 3 hours. After the reaction period the mixture was poured on crushed ice, acidified with HCl, and extracted with 1 M HCl (2×100 mL), 1 M NaHCO3 (1×100 mL), and then H2O (1×100 mL). Drying over MgSO4 followed by filtration and solvent removal resulted in the isolation of a light brown oil. Vacuum distillation resulted in the isolation of the desired product as a pale yellow oil (28.0 g, 94.3 percent yield).
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:38])([CH3:37])[O:6][C@@H:7]1[C@H:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[C@@H:10]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[O:9][C@H:8]1[N:29]1[CH:36]=[CH:35][C:33](=[O:34])[NH:32][C:30]1=[O:31])([CH3:4])[CH3:3].[O:39]([C:46]1[CH:47]=[C:48]([CH:51]=[CH:52][CH:53]=1)[CH:49]=[O:50])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>>[OH:50][CH:49]([C:48]1[CH:51]=[CH:52][CH:53]=[C:46]([O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:47]=1)[C:35]1[C:33](=[O:34])[NH:32][C:30](=[O:31])[N:29]([CH:36]=1)[C@@H:8]1[O:9][C@H:10]([CH2:20][O:21][Si:22]([C:25]([CH3:26])([CH3:27])[CH3:28])([CH3:23])[CH3:24])[C@@H:11]([O:12][Si:13]([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15])[C@H:7]1[O:6][Si:5]([C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:38])[CH3:37]
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Product: CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](n2cc(C(O)c3cccc(Oc4ccccc4)c3)c(=O)[nH]c2=O)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C

Procedure:
5-(Hydroxy-((3-phenoxy)phenyl)methyl)-2',3',5'-tris-O-((1,1-dimethylethyl)dimethylsilyl)uridine was prepared from 2',3',5'-tris-O-((1,1-dimethylethyl)dimethylsilyl)uridine according to the method of Example 1 step (i) (using 3-phenoxybenzaldehyde instead of benzophenone) as a colourless foam.
Reaction SMILES: [Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[C@@H:13]([O:15][CH3:16])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:19]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20]1.CCN(C(C)C)C(C)C>CCCCO>[Br:1][C:2]1[C:3]([N:19]2[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:20]2)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[C@@H:13]([O:15][CH3:16])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCNC1
Reactant: CO[C@@H](C)C(=O)Nc1c[nH]c2ncc(Br)c(F)c12
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: CO[C@@H](C)C(=O)Nc1c[nH]c2ncc(Br)c(N3CC[C@@H](NC(=O)OC(C)(C)C)C3)c12
Temperature: 135 °C
Yield: 60 %

Procedure:
(S)—N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide (0.6 g, 1.9 mmol), (R)-tert-butyl pyrrolidin-3-ylcarbamate (1.1 g, 5.7 mmol), and DIEA (0.99 mL, 5.7 mmol) were placed in n-BuOH (4 mL) and heated at 135° C. for 12 hours. The reaction was cooled to room temperature, concentrated, and purified by silica gel chromatography (500:15 DCM:MeOH) to give tert-butyl (R)-1-(5-bromo-3-((S)-2-methoxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate (0.55 g, 60% yield).
Reaction SMILES: [CH:1]([CH:3]([CH3:14])[C:4]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1)=O)=O.O.[NH2:16][NH2:17]>C(O)C>[CH3:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([C:4]2[C:3]([CH3:14])=[CH:1][NH:17][N:16]=2)=[CH:7][CH:8]=1
Reactant: NN
Reactant: COc1ccc(C(=O)C(C)C=O)cc1
Solvent: O
Solvent: CCO
Product: COc1ccc(-c2n[nH]cc2C)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 88 %

Procedure:
9.8 g (51.0 mmol) of the 2-formyl-4′-methoxypropiophenone synthesized in Step 1 was dissolved in 150 ml of ethanol. At room temperature, 3.8 g (61.2 mmol) of 80% hydrazine hydrate was dropwise added to the solution, followed by stirring at the same temperature for 1 hour and further by heating under reflux for 2 hours. After reaction had been completed, the reaction mixture was cooled to room temperature and the solvent was distilled away. As a result, 8.4 g (44.9 mmol) of 3-(4′-methoxyphenyl)-4-methylpyrazole was obtained as an orange oily matter. The yield was 88%. The product synthesized was subjected to the next reaction without purification.
Reaction SMILES: C[N:2]1[CH:7]=[CH:6][C:5](C2C=CC(C)=CC=2)=[CH2+:4][CH:3]1[O-].C([S@](C1C=CC(C)=CC=1)=O)=C.[O:27]1[CH2:32][CH2:31]OCC1>>[CH:3]12[NH:2][CH:7]([CH2:5][CH2:4]1)[CH:6]=[CH:31][C:32]2=[O:27]
Reactant: C1COCCO1
Reactant: Cc1ccc(C2=[CH2+]C([O-])N(C)C=C2)cc1
Agent: C=C[S@@](=O)c1ccc(C)cc1
Product: O=C1C=CC2CCC1N2

Procedure:
A solution of 1-methyl-4-(p-tolyl)-3-pyridiniumolate 26 (1.86 g, 8.37 mmol) and (+)-(R)-p-tolyl vinyl sulphoxide (1.07 g, 6.45 mmol) in dioxane (50 mL) was allowed to reflux for 20 hours. The resulting reaction mixture was concentrated under reduced pressure, purified by silica gel flash chromatography, and recrystallized from EtOAc to give the compound 29 as a white solid: [α]25D −47° (c 0.8, CH2Cl2); Rf0.6 (EtOAc); mp 188° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:7][N:6]=1)=[O:4].ClC1C=CC=C(C(OO)=[O:28])C=1>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[O:28])=[CH:7][N:6]=1)=[O:4]
Reactant: COC(=O)c1ccc(SCc2cccc(Cl)c2)cn1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COC(=O)c1ccc(S(=O)Cc2cccc(Cl)c2)cn1
Reaction time: 3 h

Procedure:
To the stirred solution of 10.28 g of 5-(m-chloro-benzylmercapto)-2-pyridinecarboxylic acid methyl ester in 150 ml of methylene chloride, cooled in an ice bath, 7.5 g of m-chloroperbenzoic acid are added in small portions during 10 minutes. The mixture is stirred for 3 hours, washed twice with 10% aqueous potassium bicarbonate, dried and evaporated. The residue is recrystallized from ethanol, to yield the 5-(m-chlorobenzylsulfinyl)-2-pyridinecarboxylic acid methyl ester of the formula ##STR6## melting at 143°-144°.
Reaction SMILES: [C@@H:1]12[CH2:7][NH:6][C@@H:5]1[CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:2]2.Br[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1>>[N:21]1[CH:22]=[CH:23][CH:24]=[C:19]([N:6]2[CH2:7][C@@H:1]3[C@H:5]2[CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:2]3)[CH:20]=1
Reactant: Brc1cccnc1
Reactant: O=C(OCc1ccccc1)N1C[C@@H]2CN[C@@H]2C1
Product: O=C(OCc1ccccc1)N1C[C@@H]2CN(c3cccnc3)[C@@H]2C1
Yield: 42 %

Procedure:
The product of Example 40A (230 mg, 1.0 mmol) and 3-bromopyridine were processed according to the procedure described in Example 1E. The crude product was purified by chromatography (SiO2, CH2Cl2:MeOH, 95:5, Rf. 0.3) to provide the title compound (130 mg, 42% yield: 1H NMR (MeOH-d4, 300 MHz) δ3.24 (dd, J=12.6, 4.1 Hz, 1H), 3.30 (m, 1H), 3.40 (m, 1H), 3.65 (dd, J=7.8, 3.4 Hz, 1H), 4.08-3.92 (m, 3H), 4.70 (m, 1H), 5.10 (m, 2H), 6.90 (m, 1H), 7.24 (m, 3H), 7.35 (m, 2H), 7.73 (d, J=2.7 Hz, 1H), 7.86 (d, J=4.7 Hz, 1H); MS (DCI/NH3) m/z 310 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[CH2:23][OH:24])=[CH:17][CH:16]=1>[O-2].[O-2].[Mn+4]>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH:13]=[CH:14][C:15]1[CH:16]=[CH:17][C:18](/[CH:21]=[CH:22]/[CH:23]=[O:24])=[CH:19][CH:20]=1
Reactant: Cc1oc(-c2ccccc2)nc1/C=C/c1ccc(/C=C/CO)cc1
Agent: [Mn+4]
Agent: [O-2]
Product: Cc1oc(-c2ccccc2)nc1C=Cc1ccc(/C=C/C=O)cc1

Procedure:
(E,E)-3-[4-[2-(5-Methyl-2-phenyl-4-oxazolyl)vinyl]phenyl]-2propenol was oxidized with activated manganese dioxide in the same manner as in Reference Example 25 to yield (E)-4-[2-(5-methyl-2-phenyl-4-oxazolyl)vinyl]cinnamaldehyde, which was then recrystallized from ethyl acetate to yield light yellow prisms having a melting point of 191°-192° C.