Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:22][C:23](=[O:35])[C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=1)[CH2:2][C:3]#[C:4][CH2:5][CH2:6][CH2:7][NH:8][C:9](=[O:21])[C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1.C(O)C.[H][H]>N1C=CC=CC=1>[CH2:1]([NH:22][C:23](=[O:35])[C:24]1[CH:25]=[CH:26][C:27]([O:30][C:31]([F:32])([F:33])[F:34])=[CH:28][CH:29]=1)[CH2:2]/[CH:3]=[CH:4]\[CH2:5][CH2:6][CH2:7][NH:8][C:9](=[O:21])[C:10]1[CH:11]=[CH:12][C:13]([O:16][C:17]([F:19])([F:20])[F:18])=[CH:14][CH:15]=1
Reactant: [H][H]
Reactant: O=C(NCCC#CCCCNC(=O)c1ccc(OC(F)(F)F)cc1)c1ccc(OC(F)(F)F)cc1
Solvent: CCO
Solvent: c1ccncc1
Product: O=C(NCC/C=C\CCCNC(=O)c1ccc(OC(F)(F)F)cc1)c1ccc(OC(F)(F)F)cc1

Procedure:
A solution containing 9.86 g. of N,N'-(3-heptyne-1,7-diyl)bis(4-trifluoromethoxybenzamide) in 110 ml. of ethanol and 5.0 ml. of pyridine was hydrogenated in a Parr shaker using 1.0 g. of palladium-on-barium sulfate using an initial pressure of hydrogen of 35.5 psi and taking about 40 minutes. The reaction mixture was filtered to remove the catalyst and the filtrate was concentrated in vacuo to remove the sulfate. The white crystalline solid residue was recrystallized from carbon tetrachloride using a small quantity of methanol to yield, as a white microcrystalline powder after drying in vacuo at 60° C. for about 50 hours, 7.6 g. of N,N'-(cis-3-heptene-1,7-diyl)bis(4-trifluoromethoxybenzamide), m.p. 111°-113° C.
Reaction SMILES: [N:1]([C@H:4]([CH2:15][OH:16])[C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6])=[N+]=[N-].[H][H]>C(OCC)(=O)C.[Pd]>[NH2:1][C@H:4]([CH2:15][OH:16])[C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6]
Reactant: [H][H]
Reactant: [N-]=[N+]=N[C@H](CO)C(=O)NCc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: N[C@H](CO)C(=O)NCc1ccccc1
Temperature: 27.5 °C

Procedure:
In an autoclave charged (2R)-2-azido-N-benzyl-3-hydroxypropanamide (68.0 gms) in ethyl acetate (680 ml). Charged catalyst 5% Pd-C (6.85 gms) and closed the autoclave. Applied 3.8 kg Hydrogen pressure maintaining temperature at 25-30° C. and maintained the reaction mixture at 25-30° C. for 1.0 hour. After completion of the reaction, released Hydrogen pressure and flushed the autoclave with Nitrogen gas. Filtered the reaction mass through hyflo bed and washed hyflo bed with ethyl acetate. Concentrated filtrate under reduced pressure at 30-35° C. till two volumes of ethyl acetate remains in the reaction mixture. Removed vacuum and cooled the reaction mass to 0-5° C. and maintained for 2.0 hours. The reaction mass was filtered and washed with cold ethyl acetate (2×40 ml). Dried the product (2R)-2-amino-N-benzyl-3-hydroxypropanamide under vacuum at 25-30° C. till constant weight.
Reaction SMILES: Br[C:2](Br)=[CH:3][C:4]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)([CH3:6])[CH3:5].C([Li])CCC.C1(O[C:27]#[N:28])C=CC=CC=1>O1CCCC1.CCCCCC.C(OCC)(=O)C.[OH-].[Na+]>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:4]([CH3:6])([CH3:5])[C:3]#[C:2][C:27]#[N:28])=[CH:8][CH:9]=1
Reactant: CC(C)(C=C(Br)Br)c1ccc(Cl)cc1
Reactant: N#COc1ccccc1
Agent: [Li]CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC(C)(C#CC#N)c1ccc(Cl)cc1
Temperature: 10 °C
Reaction time: 8 h
Yield: 81.3 %

Procedure:
A solution of 1,1-dibromo-3-(p-chlorophenyl)-3-methyl-1-butene (38.5 g, 0.113 mol) in tetrahydrofuran is treated with n-butyllithium (0.25 mol, 100 mL of a 2.5 M solution in hexane) under nitrogen over 45 minutes while maintaining the temperature below −65° C., stirred overnight at dry ice/acetone bath temperature, treated dropwise with a solution of phenyl cyanate (14.89 g, 0.125 mol) in tetrahydrofuran over 30 minutes at −65° C. to −70° C., allowed to warm to 10° C., and diluted with ethyl acetate and 5% sodium hydroxide solution. The resultant mixture is extracted with ethyl acetate. The organic extracts are combined, washed sequentially with 5% sodium hydroxide solution and water, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain a residue. The residue is distilled to give the title product as an oil (18.7 g, bp 110-113° C./0.9 mm Hg, 80.7% yield).
Reaction SMILES: Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.CC1(C)C(C)(C)OB([C:17]2[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)O1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:6]1[CH:7]=[CH:8][C:3]([C:17]2[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)=[CH:4][CH:5]=1
Reactant: CC1(C)OB(c2ccc(C(=O)O)cc2)OC1(C)C
Reactant: Brc1ccncc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: O=C(O)c1ccc(-c2ccncc2)cc1
Temperature: 80 °C
Yield: 65.3 %

Procedure:
4-Bromopyridine hydrochloride (0.4 g, 2 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (0.5 g, 2 mmol), and tetrakis(triphenylphosphine)palladium(0) (50 mg, 0.04 mmol) in dimethylformamide (15 mL) was treated with 2M potassium carbonate (2 mL) and the mixture was heated to 80° C. for 16 h. The mixture was concentrated in vacuo and the residue was diluted with water to afford a solid which was filtered to afford the title compound (0.26 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15](=[O:19])OCC)=[N:5]2.[C:20]1([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15]([N:29]1[CH2:30][CH2:31][N:26]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:27][CH2:28]1)=[O:19])=[N:5]2
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: CCOC(=O)Nc1nc2cc(Cl)ccc2nc1OC
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: COc1nc2ccc(Cl)cc2nc1NC(=O)N1CCN(c2ccccc2)CC1
Temperature: 70 °C
Reaction time: 7 h
Yield: 90.5 %

Procedure:
Ethyl N-(6-chloro-2-methoxyquinoxalin-3-yl)carbamate (27 mg, 0.10 mmol) and 1-phenylpiperazine (24 mg, 0.15 mmol) were dissolved in tetrahydrofuran (2 ml) at room temperature and thereto DBU (23 mg, 0.15 mmol) was added. The resulting mixture was stirred at 70° C. for 7 hours and concentrated under the reduced pressure to remove the solvent, and purified by SiO2 column chromatography. Extraction of the residue with a n-hexane:ethyl acetate (2:1) mixture and concentration gave 36 mg of the titled compound (yield, 91%). 1H NMR (300 MHz, CDCl3): δ 3.22-3.30 (m, 4H), 3.75-3.78 (m, 3H), 4.08-4.13 (m, 4H), 6.89-6.96 (m, 3H), 7.19-7.44 (m, 5H), 7.64-7.80 (m, 1H).
Reaction SMILES: [Li+].[B-](CC)(CC)CC.[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH2:17][C@@H:18]2[N:24]([CH:25]=1)[C:23](=[O:26])[C:22]1[CH:27]=[C:28]([O:70][CH3:71])[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]3[C:67]([O:68][CH3:69])=[CH:66][C:39]4[C:40](=[O:65])[N:41]5[CH:56]=[C:55]([C:57]6[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][CH:58]=6)[CH2:54][C@H:42]5[C:43](=O)[N:44](COCC[Si](C)(C)C)[C:38]=4[CH:37]=3)=[CH:30][C:21]=1[N:20](COCC[Si](C)(C)C)[C:19]2=O.[BH4-].[Li+]>O1CCCC1>[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH2:17][C@@H:18]2[N:24]([CH:25]=1)[C:23](=[O:26])[C:22]1[CH:27]=[C:28]([O:70][CH3:71])[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]3[C:67]([O:68][CH3:69])=[CH:66][C:39]4[C:40](=[O:65])[N:41]5[CH:56]=[C:55]([C:57]6[CH:58]=[CH:59][C:60]([O:63][CH3:64])=[CH:61][CH:62]=6)[CH2:54][C@H:42]5[CH:43]=[N:44][C:38]=4[CH:37]=3)=[CH:30][C:21]=1[N:20]=[CH:19]2
Reactant: COc1ccc(C2=CN3C(=O)c4cc(OC)c(OCCCOc5cc6c(cc5OC)C(=O)N5C=C(c7ccccc7N)C[C@H]5C(=O)N6COCC[Si](C)(C)C)cc4N(COCC[Si](C)(C)C)C(=O)[C@@H]3C2)cc1
Agent: CC[B-](CC)CC
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(C2=CN3C(=O)c4cc(OC)c(OCCCOc5cc6c(cc5OC)C(=O)N5C=C(c7ccccc7N)C[C@H]5C=N6)cc4N=C[C@@H]3C2)cc1
Yield: 14 %

Procedure:
A solution of Superhydride in dry tetrahydrofuran (1.0 M, 4.4 eq.) was added to a solution of the 2-analino compound 103 (300 mg) in dry tetrahydrofuran (5 mL) at −78° C. under an inert atmosphere. As reduction was proceeding slowly an aliquot of lithium borohydride (20 eq.) was added and the reaction mixture was allowed to return to room temperature. Water/ice was added to the reaction mixture to quench unreacted hydrides and the reaction was diluted with dichloromethane. The organic layer was washed sequentially with water (twice), citric acid and brine. Excess dichloromethane was removed by rotary evaporation under reduced pressure and the residue was redissolve in ethanol and water and treated with silica gel for 96 hours. The reaction mixture was vacuum filtered and the filtrate evaporated to dryness. The residue was subjected to flash column chromatography (silica gel, gradient chloroform/methanol). Pure fractions were collected and combined and excess eluent was removed by rotary evaporation under educed pressure to afford the pure product 104 (30 mg, 14% yield). LC/MS RT: 2.90 min, ES+726.09.
Reaction SMILES: C(N(CC)CC)C.[Si:8]([O:15][C@@H:16]([CH3:37])[C@@H:17]([OH:36])[CH2:18][CH2:19][C:20]1[C:25]2[N:26]=[C:27]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[O:28][C:24]=2[CH:23]=[CH:22][CH:21]=1)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].[CH3:38][S:39](Cl)(=[O:41])=[O:40]>ClCCl>[CH3:38][S:39]([O:36][C@H:17]([C@@H:16]([O:15][Si:8]([C:11]([CH3:14])([CH3:12])[CH3:13])([CH3:10])[CH3:9])[CH3:37])[CH2:18][CH2:19][C:20]1[C:25]2[N:26]=[C:27]([C:29]3[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=3)[O:28][C:24]=2[CH:23]=[CH:22][CH:21]=1)(=[O:41])=[O:40]
Reactant: C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](O)CCc1cccc2oc(-c3ccc(Cl)cc3)nc12
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@H](O[Si](C)(C)C(C)(C)C)[C@H](CCc1cccc2oc(-c3ccc(Cl)cc3)nc12)OS(C)(=O)=O
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
Triethylamine (0.248 ml) was added to an ice-cooled solution of (3S,4S)-4-(tert-butyldimethylsilyloxy)-1-[2-(4-chlorophenyl)-4-benzoxazolyl]-pentan-3-ol (P0006; 0.40 g) and methanesulfonyl chloride (0.139 ml) in dichloromethane (13 ml) and the mixture was stirred at 5° C. for 30 min. The mixture was washed with water, dried and evaporated. The residual oil (494 mg) was chromatographed over silica gel (15 g) eluting with a mixture of hexane and dichloromethane (2:1) to dichloromethane to give a colorless oil of (3S,4S)4-(tert-butyldimethylsilyloxy)-1-[2-(4-chlorophenyl)-4-benzoxazolyl]-3-pentyl methanesulfonate (P0007; 372 mg).
Reaction SMILES: [ClH:1].C[N:3]1C(C)=C(C)C(=O)[C:5](OCC2C=CC=CC=2)=[C:4]1OC.[CH3:22][O:23][CH2:24][C:25]1O[C:27]([CH3:40])=[CH:28][C:29](=[O:39])[C:30]=1[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(N)C>>[ClH:1].[CH2:4]([N:3]1[C:27]([CH3:40])=[CH:28][C:29](=[O:39])[C:30]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[C:25]1[CH2:24][O:23][CH3:22])[CH3:5]
Reactant: COc1c(OCc2ccccc2)c(=O)c(C)c(C)n1C
Reactant: COCc1oc(C)cc(=O)c1OCc1ccccc1
Agent: CCN
Agent: Cl
Product: CCn1c(C)cc(=O)c(OCc2ccccc2)c1COC

Procedure:
The title compound was prepared by the method outlined for 1,6-dimethyl-2-methoxy-methyl-3-benyloxy-pyridin-4(1H)-one hydrochloride, using 6.5 g (25 mmol, 1 eq.) of 2(1-methoxymethyl)-3-benzyloxy-6-methyl-pyran-4(1H)-one and 4.82 g (75 mmol, 3 eq.) of 70% aqueous ethylamine to yield the pure product 3.7 g (45.7%) after recrystallisation from methanol/diethyl ether, as a white crystalline solid m.p. 114-116° C.
Reaction SMILES: [S:1]=[C:2]1[NH:6][N:5]=[C:4]([CH2:7][C:8](O)=O)[NH:3]1.[CH3:11][C:12]([C:15]1[CH:16]=[C:17]([CH:20]=[C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:22]=1[OH:23])C=O)([CH3:14])[CH3:13].N1CCCCC1>C1(C)C=CC=CC=1.N1C=CC=CC=1>[OH:23][C:22]1[C:21]([C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:20][C:17](/[CH:8]=[CH:7]/[C:4]2[NH:3][C:2](=[S:1])[NH:6][N:5]=2)=[CH:16][C:15]=1[C:12]([CH3:14])([CH3:13])[CH3:11]
Reactant: O=C(O)Cc1n[nH]c(=S)[nH]1
Reactant: CC(C)(C)c1cc(C=O)cc(C(C)(C)C)c1O
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: CC(C)(C)c1cc(/C=C/c2n[nH]c(=S)[nH]2)cc(C(C)(C)C)c1O
Yield: 33 %

Procedure:
A solution of 2-(5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetic acid (prepared by the method described in Aust. J. Chem., 1979, 32, 161-5, Nowel W. Jacobsen, Bruce L. McCarthy, Stephanie Smith) (3.3 g, 0.021 mole) and 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzaldehyde (4.9 g, 0.021 mole) in a 2:1 mixture of toluene/pyridine (300 ml) is treated with piperidine (0.021 mole). The resulting mixture is stirred at reflux for 48 hours. The mixture is concentrated in vacuo and the residue dissolved in ether, the product is extracted from the organic phase with aqueous 1M NaOH. The combined aqueous layers are made acidic by treatment with aqueous 2M HCl, and the product extracted with a 1:1 mixture of ethyl acetate/ether. The organic layer is washed with saturated aqueous NaCl and dried over MgSO4. Filtration and concentration gives a solid which is triturated in hot isopropyl ether and filtered to provide 2.3 g (6.9 g theor., 33%) of desired (E)-2,4-dihydro-5-[2-[4-hydroxy-3,5-bis(1,1-dimethylethyl)phenyl]ethenyl]-3H-1,2,4-triazole-3-thione, mp 243° C.
Reaction SMILES: [C:1]1([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:11][N:10]=[C:9]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][C:26]([O-:28])=[O:27])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)C.[Pd]>[C:1]1([C:7]2[C:12]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:11][N:10]=[C:9]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C([O-])C=CCCCCCc1ncc(-c2ccccc2)c(-c2ccccc2)n1
Agent: [Pd]
Solvent: CCO
Product: O=C(O)CCCCCCCc1ncc(-c2ccccc2)c(-c2ccccc2)n1
Yield: 34 %

Procedure:
83 mg (0.18 mmol) of benzyl (8-(4,5-diphenylpyrimidin-2-yl)oct-2-enoate were dissolved in 15 ml of ethanol, and 50 mg of Pd/C (10%) were added. Hydrogenation was carried out under a hydrogen pressure of 2 bar for 6.5 hours. Removal of the catalyst by filtration was followed by concentration and purification of the residue by preparative HPLC (method A). 23 mg (34%) of the desired product were obtained.
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.O[CH2:13][C@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O.CN(C)C=O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:13][C@H:14]3[CH2:18][CH2:17][CH2:16][N:15]3[C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[N:3]=[C:2]([I:1])[C:10]=12
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CO
Reactant: Nc1ncnc2[nH]nc(I)c12
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1Cn1nc(I)c2c(N)ncnc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 7.1 %

Procedure:
Into a 1 L, 2-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (10 g, 38.31 mmol, 1.00 equiv), tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (15.4 g, 76.52 mmol, 2.00 equiv), PPh3 (20.1 g, 76.63 mmol, 2.00 equiv), and N,N-dimethylformamide (400 mL). DIAD (15.5 g, 76.65 mmol, 2.00 equiv) was added dropwise over 30 min. The resulting solution was stirred for 12 h at 25° C. and then diluted with 1 L of water. The resulting solution was extracted with ethyl acetate and the organic layers combined and washed with brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum and the residue was placed on a silica gel column and eluted with chloroform/methanol (100/1) to give 1.2 g (6%) of tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate as a off-white solid.
Reaction SMILES: [C:1]12([C:11](Cl)=[O:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(OCC)C.[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>C(OCC)(=O)C>[C:20]1([NH:19][C:11]([C:1]23[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]4)[CH2:2]2)[CH2:8]3)=[O:12])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Reactant: Nc1ccccc1
Solvent: CCOCC
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(Nc1ccccc1)C12CC3CC(CC(C3)C1)C2
Reaction time: 0.25 h

Procedure:
Dissolve 2.0 g. (10 mmoles) of 1-adamantane carboxylic acid chloride in 20 ml. of ethyl ether and add to 3.0 ml. (32.9 mmoles) of aniline. Stir the mixture 15 minutes, then add 20 ml. of water and 25 ml. of ethyl acetate. Separate the layers and extract the aqueous layer several times with ethyl acetate. Combine the extracts and wash with 2N hydrochloric acid, saturated sodium bicarbonate solution, and water. Dry the extract over anhydrous sodium sulfate, filter and evaporate to a residue. Crystallize the residue from ethyl acetate to obtain the product of this example, m.p. 196°-199°C.
Reaction SMILES: [C:1]([C:4]1[C:5]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=2)=[C:6]([C:20]#[N:21])[N:7]2[CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][C:8]=12)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl>[C:20]([C:6]1[N:7]2[CH2:12][CH2:11][NH:10][CH2:9][C:8]2=[C:4]([C:1]([NH2:2])=[O:3])[C:5]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=1)#[N:21]
Reactant: CC(C)(C)OC(=O)N1CCn2c(C#N)c(-c3cccc(F)c3)c(C(N)=O)c2C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#Cc1c(-c2cccc(F)c2)c(C(N)=O)c2n1CCNC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.5 %

Procedure:
To a solution of 1.05 g (2.73 mmol) of tert-butyl 8-carbamoyl-6-cyano-7-(3-fluorophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in 10 ml of dichloromethane are added slowly 2.7 ml (27 mmol) of trifluoroacetic acid. After stirring for 1 hour at room temperature, the solvent is evaporated off under reduced pressure, the residue is taken up in water and the aqueous phase is basified by addition of aqueous ammonia. The solid formed is separated out by filtration and rinsed with water, to give 0.71 g of 6-cyano-7-(3-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide in the form of a white powder after drying under reduced pressure.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]1[C:11]([C:12]2([OH:23])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([I:21])[CH:19]=3)[NH:14][C:13]2=[O:22])=[CH:10][CH:9]=[CH:8][N:7]=1)[CH3:4].[CH3:24][O:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=1[S:34](Cl)(=[O:36])=[O:35].O>CN(C=O)C.C(OCC)C>[CH3:24][O:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=1[S:34]([N:14]1[C:15]2[C:20](=[CH:19][C:18]([I:21])=[CH:17][CH:16]=2)[C:12]([C:11]2[C:6]([O:5][CH2:3][CH3:4])=[N:7][CH:8]=[CH:9][CH:10]=2)([OH:23])[C:13]1=[O:22])(=[O:35])=[O:36]
Reactant: CCOc1ncccc1C1(O)C(=O)Nc2ccc(I)cc21
Reactant: COc1ccc(S(=O)(=O)Cl)c(OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCOc1ncccc1C1(O)C(=O)N(S(=O)(=O)c2ccc(OC)cc2OC)c2ccc(I)cc21
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 255 %

Procedure:
Sodium hydride (145 mg of a 50% strength dispersion in mineral oil, 3.03 mmol) was added to an ice-cooled solution of 3-(2-ethoxypyridin-3-yl)-3-hydroxy-5-iodo-1,3-dihydroindol-2-one (1.0 g, 2.52 mmol) in DMF (20 ml). The reaction mixture was stirred at 0° C. for 15 minutes and then 2,4-dimethoxyphenylsulfonyl chloride (99 mg, 0.48 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours, water was added, and the resulting precipitate was filtered off. The precipitate formed after stirring in ethyl ether (50 ml) overnight was filtered off with suction, resulting in 730 mg of the title compound (45% yield).
Reaction SMILES: Br[C:2]1[C:3]([CH3:25])=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:5]2[N:6]([N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=2)[CH:7]=1.C([Sn](CCCC)(CCCC)[C:31]1[N:35]([C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)[N:34]=[CH:33][CH:32]=1)CCC>>[C:40]([C:39]1[CH:38]=[CH:37][C:36]([N:35]2[C:31]([C:2]3[C:3]([CH3:25])=[C:4]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:24])[F:23])[CH:16]=4)[C:5]4[N:6]([N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=4)[CH:7]=3)=[CH:32][CH:33]=[N:34]2)=[CH:43][CH:42]=1)#[N:41]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnn1-c1ccc(C#N)cc1
Reactant: CC(=O)Nc1nc2c(-c3cccc(C(F)(F)F)c3)c(C)c(Br)cn2n1
Product: CC(=O)Nc1nc2c(-c3cccc(C(F)(F)F)c3)c(C)c(-c3ccnn3-c3ccc(C#N)cc3)cn2n1

Procedure:
The title compound was prepared from the N-[6-bromo-7-methyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-acetamide (Int. 18, 65 mg, 0.157 mmol) and 4-(5-tributylstannanyl-pyrazol-1-yl)-benzonitrile (Int. 3, 79 mg, 0.173 mmol) using a similar method to that used in Example 1 (Step 4) (26 mg).
Reaction SMILES: C[O-].[Na+].[Cl:4][C:5]1[CH:6]=[C:7]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[O:8][CH:9]([CH2:22][CH3:23])[C:10]([NH:12][C:13]([CH3:21])([CH3:20])[C:14]#[C:15][CH2:16][CH2:17][CH2:18]Cl)=[O:11].[I-].[Na+].CCCCCC.[C:36](OCC)(=[O:38])C>CO.O>[Cl:4][C:5]1[CH:6]=[C:7]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[O:8][CH:9]([CH2:22][CH3:23])[C:10]([NH:12][C:13]([CH3:21])([CH3:20])[C:14]#[C:15][CH2:16][CH2:17][CH2:18][O:38][CH3:36])=[O:11]
Reactant: CCC(Oc1cc(Cl)cc(Cl)c1)C(=O)NC(C)(C)C#CCCCCl
Reactant: CCOC(C)=O
Agent: C[O-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CCCCCC
Product: CCC(Oc1cc(Cl)cc(Cl)c1)C(=O)NC(C)(C)C#CCCCOC
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a stirred solution of sodium methoxide (prepared from sodium, 0.014 g) in methanol (2 ml) at ambient temperature was added 2-(3,5-dichlorophenoxy)-N-(1-chloro-6-methylhept-4-yn-6-yl) butyramide (0.20 g) followed by further sodium methoxide (0.3 g) and sodium iodide (0.1 g). The mixture was stirred at ambient temperature under an atmosphere of nitrogen for 4 hours, heated to reflux for a total of 10 hours, cooled to ambient temperature then stored for 18 hours. The reaction mixture was diluted with water, extracted with ethyl acetate (three times) and the extracts were combined, washed with brine then evaporated under reduced pressure to give a yellow oil. The oil was fractionated by chromatography (silica; hexane/ethyl acetate, 3:1 by volume) to give the required product as a colourless oil, 0.055 g, 1H NMR (CDCl3) δ: 0.98-1.04(3H, t); 1.60(6H, s); 1.72-1.78(2H, m); 1.92-2.00(2H, m); 2.24-2.28((2H, t); 3.34(3H, s); 3.42-3.46(2H, t); 4.36-4.38(1H, t); 6.28(1H, s); 6.84(2H, s); 7.02(1H, s).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]=[O:11])[CH:8]=[CH:9][C:2]1=2.[Br:12]Br.O.C(OCC)(=O)C>C(O)(=O)C>[Br:12][C:4]1[C:3]2[CH:6]=[C:7]([CH:10]=[O:11])[CH:8]=[CH:9][C:2]=2[S:1][CH:5]=1
Reactant: BrBr
Reactant: O=Cc1ccc2sccc2c1
Solvent: O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: O=Cc1ccc2scc(Br)c2c1
Reaction time: 3 h

Procedure:
To a solution of 3 g of benzo[b]thiophene-5-carbaldehyde in 30 ml of acetic acid is dropwise added 1.43 ml of bromine with ice-cooling. The temperature of the reaction mixture is elevated to room temperature, at which temperature the mixture is stirred for three hours. After the reaction, 50 ml of water and 50 ml of ethyl acetate are added to the thus stirred reaction mixture, and the resulting organic layer was separated, washed successively with water, a saturated aqueous sodium hydrogencarbonate solution and a saturated saline solution and then dried over anhydrous magnesium sulfate. Thereafter, the solvent is removed from the thus dried layer by distillation under reduced pressure. The residue obtained is purified by a moderate pressure column chromatography [eluent:hexane:ethyl acetate=20:1], to obtain 4.2 g of 3-bromobenzo[b]thiophene-5-carbaldehyde.