Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C@@H:14]([NH:23][C:24](=[O:27])[CH2:25][CH3:26])[C@H:13]([O:28]C(=O)C)[CH2:12]4)[CH2:9][CH2:8][C:7]=2[CH:6]=1)(=O)C.[OH-].[Na+].O.Cl>C(O)C>[CH3:26][CH2:25][C:24]([NH:23][C@H:14]1[C@H:13]([OH:28])[CH2:12][C@H:11]2[C@H:10]3[C@H:19]([CH2:18][CH2:17][C@:15]12[CH3:16])[C:20]1[CH:21]=[CH:22][C:5]([OH:4])=[CH:6][C:7]=1[CH2:8][CH2:9]3)=[O:27]
Reactant: CCC(=O)N[C@H]1[C@H](OC(C)=O)C[C@H]2[C@@H]3CCc4cc(OC(C)=O)ccc4[C@H]3CC[C@@]21C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCC(=O)N[C@H]1[C@H](O)C[C@H]2[C@@H]3CCc4cc(O)ccc4[C@H]3CC[C@@]21C
Temperature: 25 °C

Procedure:
17β-Methylacetamido-oestra-1,3,5(10)-triene-3,16α-diol diacetate (19.7 g) was dissolved in ethanol (394 ml) and sodium hydroxide (50.9 ml; 2 N) was added. The resulting solution was refluxed for 1 h., cooled to room temperature and water (4 l) was added. The mixture was acidified with hydrochloric acid (2 N) and the precipitated product was filtered off and washed with water. Crystallisation from methanol-ether gave an isomeric mixture of 17β-methylacetamido-oestra-1,3,5(10)-triene-3,16α-diols (13.1 g; 83%).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[CH:11]([NH:14][CH:15]([CH3:17])[CH3:16])([CH3:13])[CH3:12]>ClCCl>[CH:11]([N:14]([CH:15]([CH3:17])[CH3:16])[C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][CH:4]=1)([CH3:13])[CH3:12]
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: CC(C)NC(C)C
Solvent: ClCCl
Product: CC(C)N(C(=O)c1ccc(Br)cc1)C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-bromobenzoyl chloride (10.0 g) in dry dichloromethane (60 mL) at 0° C. was slowly added diisopropylamine (19 mL; 3.0 eq). The reaction was stirred overnight under nitrogen and gradually warmed to room temperature. The solution was washed with two portions of water and the organics were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography eluting with 15% ethyl acetate. Near quantitative yield of product was obtained.
Reaction SMILES: O.C([O:4][C:5](=O)[CH:6]([O:8][C:9]1[C:18]([N+:19]([O-])=O)=[CH:17][C:16]2[CH2:15][CH2:14][CH2:13][CH2:12][C:11]=2[CH:10]=1)[CH3:7])C>C(O)(=O)C.[Fe]>[CH3:7][CH:6]1[O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:18]=2[NH:19][C:5]1=[O:4])[CH2:15][CH2:14][CH2:13][CH2:12]3
Reactant: CCOC(=O)C(C)Oc1cc2c(cc1[N+](=O)[O-])CCCC2
Agent: [Fe]
Solvent: O
Solvent: CC(=O)O
Product: CC1Oc2cc3c(cc2NC1=O)CCCC3
Yield: 81 %

Procedure:
In a mixture of 10 ml of glacial acetic acid with 1.25 ml of water, 2-(5,6,7,8-tetrahydro-3-nitro-2-naphthoxy)-propionic acid ethyl ester is dissolved and mixed in portions with 960 mg of iron powder. It is heated, cooled and poured onto water. The crystals are suctioned off and washed with water, dissolved again with ethyl acetate and washed with soda solution, the organic phase is washed with brine, dried with magnesium sulfate and concentrated by evaporation. 740 mg, yield 81%, results.
Reaction SMILES: [OH:1][N:2]=[C:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][CH:5]=1.[F:11][C:12]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:13]=1[C:14](O)=O.N>>[F:11][C:12]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:13]=1[C:14]1[O:1][N:2]=[C:3]([C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)[N:10]=1
Reactant: NC(=NO)c1cccnc1
Reactant: O=C(O)c1cc(F)c(F)cc1F
Agent: N
Product: Fc1cc(F)c(-c2nc(-c3cccnc3)no2)cc1F

Procedure:
The title compound was prepared according to the procedure of Example 8 using N′-hydroxynicotinimidamide (Aldrich) and 2,4,5-trifluorobenzoic acid (Aldrich). 1H NMR (300 MHz, CD3OD) δ 7.55 (td, J=10.3, 6.4 Hz, 1H), 7.64 (ddd, J=8.1, 5.0, 0.8 Hz, 1H), 8.23 (ddd, J=10.3, 8.6, 6.4 Hz, 1H), 8.56 (dt, J=8.1, 1.9 Hz, 1H), 8.75 (dd, J=5.1, 1.7 Hz, 1H), 9.29 (d, J=1.4 Hz, 1H) ppm; MS (DCI/NH3) m/z 278 (M+H)+.
Reaction SMILES: Br[CH2:2][CH2:3][C:4]([C:17]#[N:18])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[O:19]1[C:23]2[CH:24]=[CH:25][C:26]([CH2:28][CH2:29][NH:30][CH3:31])=[CH:27][C:22]=2[CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:17]([C:4]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][CH2:2][N:30]([CH2:29][CH2:28][C:26]1[CH:25]=[CH:24][C:23]2[O:19][CH2:20][CH2:21][C:22]=2[CH:27]=1)[CH3:31])#[N:18]
Reactant: CNCCc1ccc2c(c1)CCO2
Reactant: N#CC(CCBr)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CN(CCc1ccc2c(c1)CCO2)CCC(C#N)(c1ccccc1)c1ccccc1
Temperature: 25 °C

Procedure:
A mixture containing 3-bromo-1-cyano-1,1-diphenylpropane (0.3 g-see Preparation 4), N-[2-(2,3-dihydrobenzofur-5-yl)-ethyl]-N-methylamine (0.177 g-see Preparation 28), anhydrous potassium carbonate (0.276 g) and acetonitrile (25 ml) was heated under reflux for 48 hours. On cooling to room temperature, the mixture was concentrated in vacuo and the residue was partitioned between water (20 ml) and dichloromethane (40 ml). The layers were separated and the aqueous layer further extracted with dichloromethane (2×20 ml). The combined dichloromethane extracts were dried (Na2SO4) and concentrated in vacuo to give an oil which was purified by column chromatography on silica eluting with hexane containing dichloromethane (50% up to 100%) and then with dichloromethane containing methanol (0% up to 5%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as an oil, yield, 0.13 g.
Reaction SMILES: [C:1]1([C@H:7]2[CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:10]1[CH2:13][CH:12]([OH:14])[CH2:11]1.[H-].[Na+]>>[O:10]1[CH2:13][CH:12]([O:14][C@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][OH:8])[CH2:11]1
Reactant: OC1COC1
Reactant: c1ccc([C@H]2CO2)cc1
Agent: [H-]
Agent: [Na+]
Product: OC[C@H](OC1COC1)c1ccccc1
Temperature: 80 °C
Reaction time: 1 h
Yield: 25 %

Procedure:
Into a 50-mL round-bottom flask was placed (2S)-2-phenyloxirane (4 g, 33.29 mmol, 1.00 equiv) and oxetan-3-ol (16 mL). This was followed by the addition of sodium hydride (1.3 g, 32.50 mmol, 1.00 equiv, 60%) in several batches. The resulting solution was stirred for 1 h at 80° C. in an oil bath. The reaction was then quenched by the addition of 50 mL of NH4Cl (sat., aq.). The resulting solution was extracted with 2×50 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The residue was applied onto a silica gel column with PE/EA (8:1). Purification afforded 1.6 g (25%) of (2R)-2-(oxetan-3-yloxy)-2-phenylethan-1-ol (73.2) as a yellow oil.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:41]([NH2:43])=[O:42])[CH:24]=[C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([CH:34]([NH:36][CH2:37][CH:38](C)[CH3:39])[CH3:35])[CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1)(=[O:12])=[O:11])[CH3:9].[CH3:44]C(C)CN>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH:37]1([NH:36][CH:34]([C:30]2[CH:29]=[C:28]([C:25]3[CH:26]=[C:27]4[C:22](=[C:23]([C:41]([NH2:43])=[O:42])[CH:24]=3)[NH:21][CH:20]=[C:19]4[CH:16]3[CH2:17][CH2:18][N:13]([S:10]([CH2:8][CH3:9])(=[O:12])=[O:11])[CH2:14][CH2:15]3)[CH:33]=[CH:32][CH:31]=2)[CH3:35])[CH2:38][CH2:39][CH2:44]1
Reactant: CC(C)CN
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(C(C)NCC(C)C)c4)cc23)CC1
Solvent: O=C(O)C(F)(F)F
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(C(C)NC5CCC5)c4)cc23)CC1
Yield: 70.8 %

Procedure:
The title compound was prepared according to the general procedure of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-{1-[(2-methylpropyl)amino]ethyl}phenyl)-1H-indole-7-carboxamide trifluoroacetate, substituting cyclobutylamine (101 mg, 1.98 mmol) for (2-methylpropyl)amine to afford 29.1 mg of the title compound (70.8%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])([CH3:10])[CH3:9])=[N:6][CH:7]=1.C([Li])CCC.C(O[B:28]1[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]1)(C)C>C1COCC1>[Si:12]([O:11][C:8]([C:5]1[CH:4]=[CH:3][C:2]([B:28]2[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]2)=[CH:7][N:6]=1)([CH3:10])[CH3:9])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: CC(C)(O[Si](C)(C)C(C)(C)C)c1ccc(Br)cn1
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(O[Si](C)(C)C(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: -78 °C
Reaction time: 0.08 h

Procedure:
A solution of 5-bromo-2-(1-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)pyridine (1.63 g, 4.93 mmol) in THF (30 mL) was cooled to −78° C. followed by the addition of n-butyllithium (2.5 M in hexanes, 2.17 mL, 5.43 mmol). After 5 min at −78° C., 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.31 mL, 6.41 mmol) in THF (5.0 mL) was added dropwise, and the reaction was maintained at −78° C. for 10 min. The reaction was allowed to warm to room temperature, quenched with saturated NH4Cl, and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and evaporated. Flash chromatography of the crude residue (0-50% EtOAc/hexanes) afforded the title compound as a colorless solid.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([NH2:10])[CH:9]=[C:4]2[CH:3]=[CH:2]1.[F:11][C:12]1[C:20]([NH:21][S:22]([CH2:25][CH2:26][CH3:27])(=[O:24])=[O:23])=[CH:19][CH:18]=[C:17]([F:28])[C:13]=1[C:14](O)=[O:15].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[F:11][C:12]1[C:20]([NH:21][S:22]([CH2:25][CH2:26][CH3:27])(=[O:23])=[O:24])=[CH:19][CH:18]=[C:17]([F:28])[C:13]=1[C:14]([NH:10][C:8]1[CH:9]=[C:4]2[CH:3]=[CH:2][NH:1][C:5]2=[N:6][CH:7]=1)=[O:15]
Reactant: Nc1cnc2[nH]ccc2c1
Reactant: CCCS(=O)(=O)Nc1ccc(F)c(C(=O)O)c1F
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CCCS(=O)(=O)Nc1ccc(F)c(C(=O)Nc2cnc3[nH]ccc3c2)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.5 %

Procedure:
1H-Pyrrolo[2,3-b]pyridin-5-amine (9.97 g, 74.88 mmol), 2,6-difluoro-3-(propylsulfonamido)benzoic acid (23.00 g, 82.37 mmol), EDCI (15.79 g, 82.37 mmol), and HOBt (11.13 g, 82.37 mmol) were charged to a 2 L round-bottomed flask. DMF was added to give a homogeneous solution, and the reaction mixture was stirred at room temperature overnight. The solution was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with water (3×), brine, dried over Na2SO4 and concentrated to a slurry. DCM (500 mL) was added to this slurry, and the mixture was reconcentrated. Additional DCM (500 mL) was added, and the slurry was filtered, washed with DCM and dried under vacuum providing 2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide (15.49 g, 52.5%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 11.65 (br s, 1H), 10.85 (s, 1H), 9.79 (br s, 1H), 8.34-8.37 (m, 2H), 7.51-7.57 (m, 1H), 7.48-7.50 (m, 1H), 6.46-6.48 (m, 1H), 3.11-3.15 (m, 2H), 1.75-1.80 (m, 2H), 0.98-1.02 (m, 3H); m/z (APCI-pos) M+1=395.1.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([Cl:11])[CH:5]=[CH:4][N:3]=1.C([O-])(O)=O.[Na+]>CC(O)=O.[Fe]>[CH:5]1[C:6]([Cl:11])=[C:7]([NH2:8])[C:2]([Cl:1])=[N:3][CH:4]=1
Reactant: O=[N+]([O-])c1c(Cl)ccnc1Cl
Agent: [Fe]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: Nc1c(Cl)ccnc1Cl
Temperature: 40 °C

Procedure:
2,4-Dichloro-3-nitropyridine c (2.058 g, 10.7 mmol) was dissolved in HOAc (10 mL) under nitrogen. Iron powder (1.9191 g, 34.4 mmol) was added. The sample was heated at 40° C. for two hours. The reaction mixture was poured onto ice and then NaHCO3 was added to give a neutral solution. The sample was extracted with EtOAc (3×100 mL). The EtOAc extracts were washed with saturated NaHCO3 (1×100 mL). The combined aqueous layers were back extracted once with 100 mL EtOAc. The combined EtOAc extracts were dried over MgSO4, filtered, and concentrated to give 3-amino-2-4-dichloropyridine d (1.510 g, 9.26 mmol, 87%).
Reaction SMILES: ClC(Cl)C.[CH3:5][O:6][C:7]1[CH:44]=[CH:43][C:10]([CH2:11][N:12]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:13]2[N:18]=[CH:17][C:16]([C:19]3[C:20]4[CH2:33][CH2:32][NH:31][C:21]=4[N:22]=[C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)[N:24]=3)=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[I:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]=[C:53]=[O:54])=[CH:48][CH:47]=1>CN(C1C=CN=CC=1)C.O>[I:45][C:46]1[CH:51]=[CH:50][C:49]([NH:52][C:53]([N:31]2[C:21]3[N:22]=[C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)[N:24]=[C:19]([C:16]4[CH:15]=[N:14][C:13]([N:12]([CH2:11][C:10]5[CH:9]=[CH:8][C:7]([O:6][CH3:5])=[CH:44][CH:43]=5)[CH2:34][C:35]5[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=5)=[N:18][CH:17]=4)[C:20]=3[CH2:33][CH2:32]2)=[O:54])=[CH:48][CH:47]=1
Reactant: O=C=Nc1ccc(I)cc1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4)cn2)cc1
Agent: CN(C)c1ccncc1
Solvent: CC(Cl)Cl
Solvent: O
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4C(=O)Nc3ccc(I)cc3)cn2)cc1
Temperature: 25 °C

Procedure:
To dichloroethane solution (2 ml) of bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (108 mg), DMAP (2.4 mg) and 1-iodo-4-isocyanato-benzene (120 mg) were added, followed by refluxing for 3 hours. This was cooled to room temperature, followed by addition of water, and passed through Whatman tube, to obtain the desired compound as a crude product (70.2 mg, 45%).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[O:6][C:5](=[O:7])[C:4]([OH:8])=[C:3]1[C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][CH:10]=1.I[CH:21]([CH3:23])[CH3:22]>C1C=CC=CC=1>[CH3:1][C:2]1([CH3:19])[O:6][C:5](=[O:7])[C:4]([O:8][CH:21]([CH3:23])[CH3:22])=[C:3]1[C:9]1[CH:10]=[CH:11][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][CH:14]=1
Reactant: CC1(C)OC(=O)C(O)=C1c1ccc(S(C)(=O)=O)cc1
Reactant: CC(C)I
Solvent: c1ccccc1
Product: CC(C)OC1=C(c2ccc(S(C)(=O)=O)cc2)C(C)(C)OC1=O
Reaction time: 18 h

Procedure:
To a suspension of the alcohol of Step 1 (100 mg, 0.354 mmol) in benzene (5.0 mL) were added an excess of 2-iodopropane (105 mL) and Ag2CO3 (294 mg, 1.06 mmol). After a period of 18 h at 45° C., the reaction mixture was filtered over celite and washed with CH2CL2. After evaporation, the crude compound was purified by flash chromatography (35% to 40% EtOAc) to provide 70 mg of the title compound.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]([NH2:15])[CH:3]1[OH:16])=[N:10][O:11][N:12]=3.C(N(CC)CC)C.Br[CH2:26][CH2:27][CH2:28][C:29]([CH3:34])([CH3:33])[C:30](Cl)=[O:31].[Na+].[Cl-]>C(OCC)(=O)C>[CH3:1][C:2]1([CH3:17])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]([N:15]2[CH2:26][CH2:27][CH2:28][C:29]([CH3:34])([CH3:33])[C:30]2=[O:31])[CH:3]1[OH:16])=[N:10][O:11][N:12]=3
Reactant: CC1(C)Oc2cc3nonc3cc2C(N)C1O
Reactant: CC(C)(CCCBr)C(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC1(C)CCCN(C2c3cc4nonc4cc3OC(C)(C)C2O)C1=O
Temperature: 25 °C
Yield: 41 %

Procedure:
To 289 mg of (+)-7,8-dihydro-6,6-dimethyl-7-hydroxy-8-amino-6H-pyrano[2,3-f]benzo-2,1,3-oxadiazole dissolved in 5 mL of ethyl acetate were added 149 mg of triethylamine. The mixture was dropwise added with 308 mg of 5-bromo-2,2-dimethylvaleryl chloride, followed by stirring at the room temperature for one and half hours. The mixture was added with 10 mL of saturated aqueous NaCl solution and twice extracted with ethyl acetate (each 20 mL). After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was dissolved in 33 mL of dimethylformamide and was dropped with 1.24 g of 10% tetramethylammonium hydroxide solution under ice-cooling over 15-minute period. After the mixture was reacted under ice-cooling for one hour, the solvent was distilled off under reduced pressure and added with 10 mL of saturated aqueous NaCl solution and extracted twice with chloroform (each 20 mL). After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to a silica gel column chromatography (ethyl acetate:n-hexane=1:1, Rf=0.5) to obtain 174 mg of the intended compound as fine yellow crystals.
Reaction SMILES: [CH2:1]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[O:14][Si](C(C)(C)C)(C)C)[CH:2]=[CH2:3].[C-:22]#[N:23].[K+].C(O)C>O>[OH:14][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:12]=[CH:13][C:4]=1[CH2:1][CH2:2][CH2:3][C:22]#[N:23]
Reactant: [C-]#N
Reactant: C=CCc1ccc2ccccc2c1O[Si](C)(C)C(C)(C)C
Agent: [K+]
Solvent: O
Solvent: CCO
Product: N#CCCCc1ccc2ccccc2c1O
Yield: 35 %

Procedure:
A mixture of the product of Example 122 Part C (3.79 g, 0.010 mole), potassium cyanide (0.72 g, 0.011 mole), ethanol (15 mL) and water (2 mL) was heated at reflux for 20 hours. The cooled mixture was poured into water and extracted with ethyl acetate. The crude product was chromatographed with 1:1 ether/hexane and recrystallized (cyclohexane/toluene) to provide the title compound (0.73 g, 35%) as a white solid mp 76°-78°.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])[CH2:7][O:8][C:4]=2[C:3]=1[CH2:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.[O:26]([CH2:33][CH2:34]O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>C1COCC1>[O:9]=[C:6]1[C:5]2[CH:10]=[CH:11][C:2]([O:1][CH2:34][CH2:33][O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:3]([CH2:12][N:13]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]3)[C:4]=2[O:8][CH2:7]1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2c(O)ccc3c2OCC3=O)CC1
Reactant: OCCOc1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCN(Cc2c(OCCOc3ccccc3)ccc3c2OCC3=O)CC1
Temperature: 70 °C
Reaction time: 3 h
Yield: 53.5 %

Procedure:
A solution of tert-butyl 4-[(6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl]piperazine-1-carboxylate (0.100 g, 0.287 mmol), 2-phenoxyethanol (0.0475 g, 0.344 mmol) and triphenylphosphine (0.113 g, 0.431 mmol) in THF (2 mL) was added with a solution of a 40% solution of diethyl azodicarboxylate in toluene (0.225 g, 0.517 mmol) in THF (0.5 mL), and the mixture was stirred at 70° C. for 3 hours in a sealed tube. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography (chloroform/ethyl acetate) to obtain tert-butyl 4-[(3-oxo-6-(2-phenoxyethoxy)-2,3-dihydrobenzofuran-7-yl)methyl]piperazine-1-carboxylate (0.0720 g, 53%).
Reaction SMILES: [F:1][C:2]([S:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]([OH:16])=O)=[CH:8][CH:7]=1)([F:4])[F:3].C(Cl)(=O)C(Cl)=O.[NH3:23]>O1CCCC1.CN(C)C=O>[F:1][C:2]([S:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]([NH2:23])=[O:16])=[CH:8][CH:7]=1)([F:4])[F:3]
Reactant: O=C(O)C=Cc1ccc(SC(F)(F)F)cc1
Reactant: N
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: NC(=O)C=Cc1ccc(SC(F)(F)F)cc1
Temperature: 2.5 °C
Reaction time: 3 h

Procedure:
To a suspension of 5.24 g (21.1 mmol) 3-(4-trifluoromethylsulfanyl-phenyl)-acrylic acid in 30.0 ml tetrahydrofuran and 0.3 ml N,N-dimethyl formamide a solution of 2.75 ml (32.0 mmol) oxalyl chloride in 5.0 ml tetrahydrofuran was added dropwise at 0° C. within 20 min. Stirring was continued at 0-5° C. for 30 min. and 3 h at room temperature thereafter. The resulting solution was cooled to 0-5° C. again and then added within 15 min. to 100 ml of a 25% aqueous ammonia solution. After evaporation of the organic solvent, 200 ml water were added and the solution cooled. The precipitated amide was collected, washed with water and n-heptane and dried at 40° C. in vacuo. Yield 4.62 g (86%) 3-(4-trifluoromethylsulfanyl-phenyl)-acrylamide
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[NH:12]1)[CH2:8]2.[CH3:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH2:21]Br>>[CH3:16][C:13]1([CH3:17])[N:12]([CH2:18][C:19]2[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=2[CH3:21])[N:11]([CH:2]2[CH:3]3[CH2:4][CH:5]4[CH2:6][CH:7]([CH2:8][CH:1]2[CH2:10]4)[CH2:9]3)[C:14]1=[O:15]
Reactant: Cc1ccccc1CBr
Reactant: CC1(C)NN(C2C3CC4CC(C3)CC2C4)C1=O
Product: Cc1ccccc1CN1N(C2C3CC4CC(C3)CC2C4)C(=O)C1(C)C

Procedure:
2-(Adamantan-2-yl)-4,4-dimethyl-1,2-diazetidin-3-one and 2-methylbenzyl bromide were used for a similar reaction and treatment as Process 6 of Example 1, and the title compound was obtained as a white crystalline powder.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@@H:15]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=3)[CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Sn]([N:44]=[N+:45]=[N-:46])(CCCC)CCCC)CCC.C(O)(=O)C.[OH-].[Na+]>ClC1C=CC=CC=1Cl>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@@H:15]([C:23]3[CH:24]=[CH:25][C:26]([C:29]4[NH:46][N:45]=[N:44][N:30]=4)=[CH:27][CH:28]=3)[CH2:16][C:17]3[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-]
Reactant: COc1ccc([C@H](Cc2ccncc2)c2ccc(C#N)cc2)cc1OC1CCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: Clc1ccccc1Cl
Solvent: CC(=O)O
Product: COc1ccc([C@H](Cc2ccncc2)c2ccc(-c3nnn[nH]3)cc2)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 87.8 %

Procedure:
A solution of (R)-4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]benzene-nitrile from Step 1 (350 mg, 0.88 mmol) and tributyltin azide (1.17 g, 3.5 mmol) in 1,2-dichlorobenzene (4 mL) was stirred at 150° C. for 2 hours. The reaction mixture was then cooled to room temperature and acetic acid (0.5 mL) was added. After 15 min, aqueous 1N NaOH was added and the aqueous phase was washed 3 times with ether. The aqueous phase was then treated with 25% aqueous NH4OAc and 6N HCl to pH 7 before it was extracted twice with CH2Cl2. The organic phase was then dried (MgSO4) and evaporated to afford the title compound as a yellow solid (341 mg, 88%). 1H NMR (400 MHz, CDCl3): d 1.55 (m, 2H), 1.80 (m, 6H), 3.30 (m, 1H), 3.45 (m, 1H), 3.80 (s, 3H), 4.20 (m, 1H), 4.70 (m, 1H), 6.70 (s, 1H), 6.80 (m, 2H), 7.00 (d, 2H), 7.20 (d, 2H), 7.90 (d, 2H), 8.40 (d, 2H).
Reaction SMILES: [CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].[C:6]([C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1)(=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH2:1]([NH:5][C:18](=[O:19])[C:17]1[CH:16]=[CH:15][C:14]([C:6](=[O:13])[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:22][CH:21]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)CN
Reactant: O=C(Cl)c1ccc(C(=O)c2ccccc2)cc1
Product: CC(C)CNC(=O)c1ccc(C(=O)c2ccccc2)cc1

Procedure:
N-iso-butylamine was reacted with p-benzoylbenzoic acid chloride to provide N-iso-butyl-p-benzoyl benzamide. At a 4% by weight loading in the test solution described in Example 1, a cure rate of 7.5 - 10 ft./min./lamp was observed for several samples.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([C:21]4[C:29]5[O:28][CH2:27][O:26][C:25]=5[CH:24]=[CH:23][C:22]=4[O:30][CH2:31][CH:32]4[CH2:34][CH2:33]4)[C:15]=3[NH:14][C:13]=2[CH3:35])=[O:11])[CH2:5][CH2:4]1.[C:36](Cl)(=[O:38])[CH3:37]>>[C:36]([NH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([C:21]4[C:29]5[O:28][CH2:27][O:26][C:25]=5[CH:24]=[CH:23][C:22]=4[O:30][CH2:31][CH:32]4[CH2:34][CH2:33]4)[C:15]=3[NH:14][C:13]=2[CH3:35])=[O:11])[CH2:5][CH2:4]1)(=[O:38])[CH3:37]
Reactant: Cc1[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc2c1C(=O)N[C@H]1CC[C@H](N)CC1
Reactant: CC(=O)Cl
Agent: Cl
Product: CC(=O)N[C@H]1CC[C@H](NC(=O)c2c(C)[nH]c3c(-c4c(OCC5CC5)ccc5c4OCO5)ncnc23)CC1

Procedure:
Starting from N-(trans-4-aminocyclohexyl)-4-[5-(cyclopropylmethoxy)-1,3-benzodioxol-4-yl]-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-7-carboxamide hydrochloride (example D.f2) and commercially available acetyl chloride the title compound is obtained as colorless solid.