Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[S:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3]1.[OH-].[Na+].S1C2CCNCC=2C=C1.[CH2:22]([O:24][C:25](=[O:43])[C:26]([CH3:42])([CH3:41])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])[CH3:23].C(=O)([O-])[O-].[K+].[K+]>O.CN(C=O)C>[CH2:22]([O:24][C:25](=[O:43])[C:26]([CH3:42])([CH3:41])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])[N:7]1[CH2:8][CH2:9][C:10]2[S:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[CH3:23]
Reactant: c1cc2c(s1)CCNC2
Reactant: CCOC(=O)C(C)(C)CCCCCC(Br)c1ccccc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C(C)(C)CCCCCC(c1ccccc1Cl)N1CCc2sccc2C1
Temperature: 67.5 °C
Reaction time: 18 h
Yield: 43.5 %

Procedure:
4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride (1.30 g, 7.19 mmol) was added to sodium hydroxide (1.38 g) in water (86 mL) and extracted with dichloromethane (3×20 mL). The dichloromethane was dried over sodium sulfate, filtered, and concentrated to prepare the free base (1.0 g). 4,5,6,7-Tetrahydrothieno[3,2-c]pyridine free base (1.0 g, 7.19 mmol) and 8-bromo-8-(2-chlorophenyl)2,2-dimethyloctanoic acid ethyl ester (2.8 g, 7.19 mmol) were dissolved in DMF (75 mL) with potassium carbonate (1.49 g, 10.79 mmol). The mixture was heated to 65-70° C. overnight. After 18 hours, the mixture was cooled to room temperature and water (50 mL) was added. The product was extracted with diethyl ether (3×50 mL). The combined organic extracts were washed with water (3×50 mL), dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with ethyl acetate/heptane (1/10) to provide 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester (Compound In, 1.4 g, 43.5%) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CDCl3/TMS) δ (ppm): 7.49 (dd, 1H, J=7.5, 1.5 Hz), 7.35 (dd, 1H, J=8.1, 1.2 Hz), 7.24 (dt, 1H, J=7.5, 1.0 Hz), 7.16 (dt, 1H, J=7.8, 1.5 Hz), 7.02 (d, 1H, J=5.0 Hz), 6.68 (d, 1H, J=5.0 Hz), 4.18 (dd, 1H, J=8.7, 4.2 Hz), 4.08 (q, 2H, J=6.9 Hz), 3.82 (d, 1H, J=14.1 Hz), 3.48 (d, 1H, J=14.1 Hz), 2.88-2.66 (m, 4H), 1.96-1.76 (m, 2H), 1.46-1.41 (m, 2H), 1.26-1.18 (m, 6H), 1.21 (t, 3H, J=6.9 Hz), 1.11 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 177.92, 134.92, 134.21, 133.53, 129.48, 129.06, 127.94, 126.77, 125.44, 122.60, 63.67, 60.27, 50.73, 48.08, 42.29, 40.85, 33.02, 30.52, 26.13, 25.39, 25.01, 14.51. HRMS (FIA-ESI-TOFM): Calculated for C25H34ClNO2S (M+H)+: 448.2072, found 448.2067.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Cl:15][C:16]1[N:21]=[C:20](Cl)[CH:19]=[CH:18][N:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[Cl:15][C:16]1[N:21]=[C:20]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH:19]=[CH:18][N:17]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Clc1ccnc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccnc(Cl)n2)CC1
Temperature: 80 °C
Yield: 80.7 %

Procedure:
To tert-butyl 4-hydroxypiperidine-1-carboxylate (389 mg, 1.933 mmol) and 2,4-dichloropyrimidine (240 mg, 1.611 mmol) in DMF (6.4 mL) was added cesium carbonate (1050 mg, 3.22 mmol) and the mixture was heated at 80° C. for 1 h and then to 70° C. overnight. TLC indicated no remaining 2,4-dichloropyrimidine. The reaction was cooled to ambient temperature, diluted with water and extracted with ethyl acetate. The organic layer was washed with water (3×) and brine. The combined organic layer was dried (MgSO4), filtered and solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel to give tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate (410 mg, 1.3 mmol, 81%) as white solid. MS ESI: [M+H]+ m/z 314.2.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[CH:6]=[CH:7][C:8]([OH:10])=[O:9].[H][H]>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:6][CH2:7][C:8]([OH:10])=[O:9])[CH:11]=[CH:12][CH:13]=1
Reactant: [H][H]
Reactant: COc1cccc(C=CC(=O)O)c1
Agent: [Pd]
Solvent: CCO
Product: COc1cccc(CCC(=O)O)c1

Procedure:
Ten grams of m-methoxycinnamic acid in 100 ml. of ethanol is hydrogenated with 0.5 g. of pre-reduced 10% palladium-on-charcoal until the uptake of hydrogen ceases. The catalyst is removed by filtration and the filtrate evaporated to yield 3-(m-methoxyphenyl)propionic acid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10](Br)[CH:11]=1)=[O:5])[CH3:2].[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[C:33]([F:40])[CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10]([C:34]2[CH:35]=[CH:36][C:31]([O:30][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[CH:32][C:33]=2[F:40])[CH:11]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc(Br)nc2c1c(C)nn2C1CCCCO1
Reactant: OB(O)c1ccc(OCc2ccccc2)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: CCOC(=O)c1cc(-c2ccc(OCc3ccccc3)cc2F)nc2c1c(C)nn2C1CCCCO1
Temperature: 85 °C
Reaction time: 1.5 h
Yield: 82.4 %

Procedure:
To mixture of 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (21.0 g), 4-benzyloxy-2-fluorophenylboronic acid (16.8 g) and potassium carbonate (8.7 g) in DME/water (v/v=2/1, 300 mL) was added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.99 g) and the mixture was stirred at 85° C. for 90 min. To the mixture water was added and extracted with ethyl acetate. The organic phase was washed several times with water, finally with brine. Methanol was added and the precipitate formed was filtered off, dried in air to give 6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (23.0 g, 82% yield). This material was dissolved in isopropanol (100 mL), and 1N sodium hydroxide solution (140 mL) was added. The solution was stirred overnight, filtered, then the filtrate was adjusted to pH2-3 and the precipitate formed was dried in air giving 6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (18 g, 83%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[OH:9].C1N2CN3CN(C2)CN1C3.[C:20](O)(C(F)(F)F)=[O:21]>>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([F:8])[C:3]=1[OH:9])[CH:20]=[O:21]
Reactant: O=C(O)C(F)(F)F
Reactant: Oc1c(F)cccc1F
Agent: C1N2CN3CN1CN(C2)C3
Product: O=Cc1cc(F)c(O)c(F)c1
Temperature: 25 °C
Yield: 73 %

Procedure:
A stirring solution of 2,6-difluorophenol (2 g, 15.4 mmol) and hexamethylenetetramine (2.16 g, 15.4 mmol) in TFA (16 mL) was heated at reflux under argon overnight. On cooling to room temperature the solvent was evaporated in vacuum and the crude residue was taken up in DCM (35 mL). The mixture was washed with an aqueous solution of NaHCO3 (sat.) and the separated aqueous layer acidified to pH 1 with concentrated HCl. The aqueous layer was extracted with DCM (2×25 mL), the combined organic fractions dried (MgSO4) and evaporated in vacuum to afford desired product as a cream solid (1.76 g, 73%). Rf=0.39 (SiO2; cyclohexane/EtOAc (6/4); UV) 1H NMR (300 MHz; CDCl3) δ: 6.38 (br, 1H); 7.50 (d, 2H, J=6.6 Hz); 9.82 (s, 1H). 13C NMR (75 MHz; CDCl3) δ: 113.2 (dd, JCF=13.8 Hz and 7.8 Hz); 128.2 (t, JCF=6.0 Hz); 139.0 (t, JCF=16.1 Hz); 151.9 (dd, JCF=246.9 Hz and 5.3 Hz); 189.1. 19F NMR (282 MHz; CDCl3) δ: −52.2
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([O:17][CH:18]([CH3:20])[CH3:19])[C:12]([O:14]CC)=[O:13])=[CH:6][CH:5]=1.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1>>[CH:18]([O:17][CH:11]([CH2:10][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][CH2:2][O:1][C:30](=[O:31])[NH:29][C:26]2[CH:27]=[CH:28][C:23]([C:22]([F:21])([F:33])[F:32])=[CH:24][CH:25]=2)=[CH:9][CH:8]=1)[C:12]([OH:14])=[O:13])([CH3:19])[CH3:20]
Reactant: O=C=Nc1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)C(Cc1ccc(CCO)cc1)OC(C)C
Product: CC(C)OC(Cc1ccc(CCOC(=O)Nc2ccc(C(F)(F)F)cc2)cc1)C(=O)O

Procedure:
Using ethyl 3-[4-(2-hydroxyethyl)phenyl]-2-isopropoxypropanoate and α,α,α-trifluoro-p-tolylisocyanate, the title compound was obtained in the same manner as described in Example 148.
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:25])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([Br:21])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:22]([NH2:24])=[O:23])=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH:26]([C:28]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:29]=1[C:30]([OH:32])=[O:31])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl.O1CCCC1>[Br:21][C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]([C:4]4[C:3]([CH3:25])=[C:2]([NH:1][CH2:26][C:28]5[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:29]=5[C:30]([OH:32])=[O:31])[CH:7]=[CH:6][CH:5]=4)=[CH:9][N:10]=[C:11]([C:22](=[O:23])[NH2:24])[C:12]=3[NH:13]2)=[CH:18][CH:17]=1
Reactant: Cc1c(N)cccc1-c1cnc(C(N)=O)c2[nH]c3cc(Br)ccc3c12
Reactant: COc1ccc(C=O)c(C(=O)O)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CC(=O)O
Product: COc1ccc(CNc2cccc(-c3cnc(C(N)=O)c4[nH]c5cc(Br)ccc5c34)c2C)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 163.1 %

Procedure:
A mixture of 4-(3-amino-2-methylphenyl)-7-bromo-9H-pyrido[3,4-b]indole-1-carboxamide (0.184 g, 0.466 mmol), 2-formyl-5-methoxybenzoic acid (0.210 g, 1.164 mmol), sodium triacetoxyborohydride (0.296 g, 1.397 mmol), and acetic acid (0.067 mL, 1.164 mmol) in dichloromethane (14 mL) and tetrahydrofuran (14 mL) was stirred at room temperature for 16 hr. The reaction was quenched with water (30 mL) and the mixture was extracted with ethyl acetate (3×40 mL). The combined extract was washed with brine (30 ml) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the crude desired product (0.425 g, 0.760 mmol, 163% yield) as a beige solid. The crude product was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:7](=[O:9])[CH3:8])[S:5][CH:6]=1.FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C([I:21])C=CC=1)=O.II>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl>[I:21][C:6]1[S:5][C:4]([C:7](=[O:9])[CH3:8])=[CH:3][C:2]=1[CH3:1]
Reactant: O=C(Oc1cccc(I)c1OC(=O)C(F)(F)F)C(F)(F)F
Reactant: CC(=O)c1cc(C)cs1
Agent: II
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: CC(=O)c1cc(C)c(I)s1
Reaction time: 2 h
Yield: 66.2 %

Procedure:
Commercially available 1-(4-Methyl-thiophen-2-yl)-ethanone (2.0 g, 14.2 mmol) was combined with bis(trifluoroacetoxy)iodobenzene (6.3 g, 14.2 mmol) and iodine (3.6 g, 14.2 mmol) in CCl4 (30 ml). The purple suspension was stirred for 2 h upon which time the reaction was judged to be complete by HPLC. The reaction was diluted with CH2Cl2 and washed with Na2S2O3 (aq, sat.) until the purple color dissipated. The organics were washed with H2O and brine. The aqueous layers were extracted once with CH2Cl2 and the combined organics were dried (Na2SO4), filtered and concentrated by rotary evaporation to give a yellow residue which was purified by flash column chromatography (hexanes:ethyl acetate gradient 2–50% ethyl acetate) to give 1-(5-Iodo-4-methyl-thiophen-2-yl)-ethanone (2.5 g, 66%) as a solid; MS (ESI) m/z 266.9 (M+H+); 1H NMR (300 MHz, DMSO-d6) δ 7.65 (s, 1H), 2.47 (s, 3H), 2.19 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]([OH:13])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23]O)=[O:20])([CH3:17])([CH3:16])[CH3:15]>>[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][O:13][C:10]1[CH:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[O:12][N:11]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15]
Reactant: Oc1cc(-c2cccc(Cl)c2)on1
Reactant: CC(C)(C)OC(=O)NCCO
Product: CC(C)(C)OC(=O)NCCOc1cc(-c2cccc(Cl)c2)on1
Yield: 85.3 %

Procedure:
5-(3-Chlorophenyl)-3-hydroxyisoxazole (0.23 g) and 2-(N-tert-butoxycarbonylamino)ethanol (0.20 g) were subjected to reaction and post-treatment in a similar manner to that described in Example 9(a) to obtain the title compound (0.34 g, 85%) as a colorless powder.
Reaction SMILES: [NH:1]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:2]([C:11](O)=[O:12])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C(=O)(O)[O-].[NH4+].C[N:42](C)C=O>C1(C)C=CC=CC=1.O.N1C=CC=CC=1>[NH2:42][C:11](=[O:12])[C@@H:2]([NH:1][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:3][C:4]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:10]
Reactant: CC(C)(C)OC(=O)C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: CN(C)C=O
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [NH4+]
Solvent: O
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)C[C@H](NC(=O)OC(C)(C)C)C(N)=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
360.0 g of the starting material, N-Boc-Asp(O-t-Bu)OH, together with Boc2O (353.0 g) and ammonium bicarbonate (NH4HCO3, 123.9 g) was added to dimethylformamide (1174.6 g), and pyridine (61.0 g) was added dropwise thereto at room temperature, and the reaction mixture was then stirred for about 3 hours. Upon completion of the reaction, water (1440 ml) and toluene (1800 ml) were added to the reaction solution and stirred for 30 minutes to separate the layers. The organic layer thus obtained was distilled under reduced pressure to remove t-butanol and toluene to obtain the title compound, which was directly used in the next reaction.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4]([OH:7])(=[O:6])=[O:5].Cl[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].C(=O)([O-])[O-].[Na+].[Na+]>O>[CH2:12]([O:11][C:9]([NH:1][CH2:2][CH2:3][S:4]([OH:7])(=[O:6])=[O:5])=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: NCCS(=O)(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=C(NCCS(=O)(=O)O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of taurine (12.5 g, 100 mmol), benzyl chloroformate (15.1 mL, 105 mmol) and sodium carbonate (10.6 g, 100 mmol) in water (250 mL) was stirred at room temperature for overnight. The product mixture was extracted with diethyl ether. The organic extract was concentrated under vacuum to provide 2-{[(benzyloxy)carbonyl]-amino}ethanesulfonic acid. Without further purification, the sulfonic acid was treated with thionyl chloride (15 mL, 206 mmol) with external ice-water bath cooling. The resultant mixture was stirred at room temperature for 1 hour, and poured into ice water. The mixture was extracted with diethyl ether. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to provide the title compound as white solid.
Reaction SMILES: [CH3:1][C:2]1([CH2:9][OH:10])[CH2:7][CH2:6][CH:5]=[C:4]([CH3:8])[O:3]1.[CH2:11](Cl)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>[OH-].[Na+].C(Cl)Cl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH3:1][C:2]1([CH2:9][O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6][CH:5]=[C:4]([CH3:8])[O:3]1
Reactant: ClCc1ccccc1
Reactant: CC1=CCCC(C)(CO)O1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CC1=CCCC(C)(COCc2ccccc2)O1
Temperature: 25 °C
Reaction time: 21 h
Yield: 80.2 %

Procedure:
A mixture of 3,4-dihydro-2,6-dimethyl-2H-pyran-2-methanol (5.8 g) and benzyl chloride (5.2 g) in 50% aqueous sodium hydroxide (16 g) and 10 ml methylene chloride was treated with 0.7 g tetrabutylammonium hydrogen sulfate. After stirring vigorously for 21 hours at room temperature, the mixture was diluted with more methylene chloride and water to facilitate phase separation. The organic phase was separated, washed with water, dried over potassium carbonate and concentrated. Distillation gave 7.6 g colorless liquid with bp 101°-102° C. (0.02 torr).
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:6]([CH3:8])([CH3:7])[O:5][B:4](C2CC3(CC(C(OC)=O)C3)C=2)[O:3]1.FC(F)(F)S(O[C:27]1[CH2:32][CH2:31][CH:30]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:29][CH:28]=1)(=O)=O>>[CH3:1][C:2]1([CH3:20])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:27]2[CH2:32][CH2:31][CH:30]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:29][CH:28]=2)[O:3]1
Reactant: CCOC(=O)CC1CC=C(OS(=O)(=O)C(F)(F)F)CC1
Reactant: COC(=O)C1CC2(C=C(B3OC(C)(C)C(C)(C)O3)C2)C1
Product: CCOC(=O)CC1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Yield: 99 %

Procedure:
The title compound was prepared following the method described in step 2 for the preparation of methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[3.3]hept-5-ene-2-carboxylate, using ethyl 2-(4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-en-1-yl)acetate as the reactant. (99% yield), MS: m/e 295.2 (M+H)+, 2.28 min (method 3). 1H NMR (400 MHz, CHLOROFORM-d) δ 6.54 (d, J=2.3 Hz, 1H), 4.15 (q, J=7.3 Hz, 2H), 2.41-1.99 (m, 7H), 1.93-1.71 (m, 2H), 1.38-1.22 (m, 15H).
Reaction SMILES: [NH2:1][N:2]1[C:7](=[O:8])[C:6]2[S:9][CH:10]=[CH:11][C:5]=2[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:3]1.[OH:18][C:19]12[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:27][C:21]([CH2:29][C:30](O)=[O:31])([CH2:22]3)[CH2:20]1)[CH2:26]2>>[OH:18][C:19]12[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:27][C:21]([CH2:29][C:30]([NH:1][N:2]4[C:7](=[O:8])[C:6]5[S:9][CH:10]=[CH:11][C:5]=5[C:4]([C:12]5[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=5)=[N:3]4)=[O:31])([CH2:22]3)[CH2:20]1)[CH2:26]2
Reactant: O=C(O)CC12CC3CC(CC(O)(C3)C1)C2
Reactant: Nn1nc(-c2ccccc2)c2ccsc2c1=O
Product: O=C(CC12CC3CC(CC(O)(C3)C1)C2)Nn1nc(-c2ccccc2)c2ccsc2c1=O

Procedure:
The product from Example 29B and 2-(3-hydroxyadamantan-1-yl)acetic acid were processed using a method similar to that described in Example 17C to afford the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 11.37 (s, 1H), 8.35 (d, J=5.2 Hz, 1H), 7.70-7.73 (m, 2H), 7.56-7.58 (m, 4H), 4.39 (s, 1H), 2.12 (s, 2H), 2.07-2.12 (m, 2H), 1.41-1.62 (m, 12H); MS (APCI+) M/Z 436 (M+H)+.
Reaction SMILES: [CH2:1]([C:3]1[O:4][CH2:5][CH2:6][N:7]=1)[CH3:2].[C:8]([NH2:12])([CH3:11])([CH3:10])[CH3:9]>C([O-])(=O)C.[Zn+2].C([O-])(=O)C>[C:8]([NH:12][CH2:5][CH2:6][NH:7][C:3](=[O:4])[CH2:1][CH3:2])([CH3:11])([CH3:10])[CH3:9]
Reactant: CC(C)(C)N
Reactant: CCC1=NCCO1
Agent: CC(=O)[O-]
Agent: [Zn+2]
Product: CCC(=O)NCCNC(C)(C)C
Yield: 64 %

Procedure:
Under the same conditions as Example 13, 2.5 gm (25 mmoles) of 2-ethyl-2-oxazoline, 1.84 gm (25 mmoles) of t-butylamine and 49.4 mg (0.27 mmole) of zinc acetate are reacted to yield 64 percent N-(2-t-butylaminoethyl)propionamide.
Reaction SMILES: [CH:1]([C:3]1[NH:4][C:5]([CH3:11])=[CH:6][C:7]=1[C:8]([OH:10])=O)=[O:2].[N:12]1([CH2:17][CH2:18][NH2:19])[CH:16]=[CH:15][N:14]=[N:13]1>>[N:12]1([CH2:17][CH2:18][NH:19][C:8]([C:7]2[CH:6]=[C:5]([CH3:11])[NH:4][C:3]=2[CH:1]=[O:2])=[O:10])[CH:16]=[CH:15][N:14]=[N:13]1
Reactant: Cc1cc(C(=O)O)c(C=O)[nH]1
Reactant: NCCn1ccnn1
Product: Cc1cc(C(=O)NCCn2ccnn2)c(C=O)[nH]1
Yield: 79 %

Procedure:
2-Formyl-5-methyl-1H-pyrrole-3-carboxylic acid (2.0 g, 13.06 mmol) reacted with 2-[1,2,3]triazol-1-yl-ethylamine (1.76 g, 15.67 mmol) to give 2.55 g (79%) of 2-formyl-5-methyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide.
Reaction SMILES: [Cl:1][C:2]1[C:9]([CH3:10])=[C:8](I)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].NC1C=CC(C#N)=C(Cl)C=1C.[CH3:23][C:24]1([CH3:32])[C:28](=[O:29])[CH:27]([CH3:30])[NH:26][C:25]1=[O:31].C(=O)([O-])[O-].[Cs+].[Cs+].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>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([N:26]2[CH:27]([CH3:30])[C:28](=[O:29])[C:24]([CH3:32])([CH3:23])[C:25]2=[O:31])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: CC1NC(=O)C(C)(C)C1=O
Reactant: Cc1c(I)ccc(C#N)c1Cl
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: Cc1c(N)ccc(C#N)c1Cl
Product: Cc1c(N2C(=O)C(C)(C)C(=O)C2C)ccc(C#N)c1Cl

Procedure:
Using 2-chloro-4-iodo-3-methylbenzonitrile (894 mg) synthesized from 4-amino-2-chloro-3-methylbenzonitrile in the same method as in Reference Example 8, 3,3,5-trimethylpyrrolidine-2,4-dione (350 mg), cesium carbonate (1.21 g), tris(dibenzylideneacetone)dipalladium(0) (227 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (287 mg), and in the same manner as in Reference Example 3, the title compound was obtained as a colorless solid (yield: 46 mg, 6%).
Reaction SMILES: B.CSC.[O:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]1[O:11][C:12]1[CH:30]=[CH:29][C:15]([O:16][CH:17]([C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=2)[CH2:18][CH:19]=[CH2:20])=[CH:14][CH:13]=1.O.CC[O:34]CC>C1COCC1>[OH:34][CH2:20][CH2:19][CH2:18][CH:17]([C:21]1[CH:22]=[CH:23][C:24]([C:25]#[N:26])=[CH:27][CH:28]=1)[O:16][C:15]1[CH:29]=[CH:30][C:12]([O:11][CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10][O:5]2)=[CH:13][CH:14]=1
Reactant: CCOCC
Reactant: C=CCC(Oc1ccc(OC2CCCCO2)cc1)c1ccc(C#N)cc1
Agent: B
Solvent: CSC
Solvent: O
Solvent: C1CCOC1
Product: N#Cc1ccc(C(CCCO)Oc2ccc(OC3CCCCO3)cc2)cc1
Reaction time: 1.5 h
Yield: 58 %

Procedure:
Borane-dimethylsulfide complex (3.5 mL of 2 M in ether, 7 mmol) was added dropwise to a cooled (5° C.) solution of 4-{1-[4-(tetrahydro-2H-pyran-2-yloxy)phenoxy]-3-butenyl}benzonitrile (see step (i) above; 4.6 g, 13 mmol) in dry THF over a period of 15 min. The resulting mixture was stirred at between 0 and 5° C. for 1.5 h. Stirring was then continued for a further 4 h at rt. Water (14 mL) and NaBO3 (5 g) were added and the mixture stirred overnight. Ether was added and the resulting organic layer was separated, washed with water and brine, dried and then evaporated. The resulting residue was purified by chromatography on silica gel, eluting with IPA:EtOAc:heptane (5:20:70), to give 2.44 g (58%) of the sub-title compound.
Reaction SMILES: [I:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]([CH2:12][NH:13]C(=O)C[Cl:16])[C:3]=1[OH:18].Cl>C(O)C>[ClH:16].[I:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]([CH2:12][NH2:13])[C:3]=1[OH:18]
Reactant: O=C(CCl)NCc1cc2c(c(I)c1O)CCCC2
Agent: Cl
Solvent: CCO
Product: NCc1cc2c(c(I)c1O)CCCC2
Yield: 70.4 %

Procedure:
A solution of 1.08 g of N-chloroacetylamino compound (prepared in Example 2) in 10 ml of ethanol was mixed with 2 ml of concentrated hydrochloric acid and heated under reflux for 5 hours. The reaction mixture was concentrated under vacuum, and the residue was recrystallized from a solvent comprising a mixture of methanol and diethyl ether, giving 680 mg of a white crystal of the title compound having the following physical properties.