Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18](Br)=[CH:17][C:16]=2[CH2:22][N:23]2[CH2:27][CH2:26][O:25][C:24]2=[O:28])[CH:7]=1)[CH3:2].[CH3:30][S:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O)(=[O:33])=[O:32]>>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[S:31]([CH3:30])(=[O:33])=[O:32])=[CH:17][C:16]=2[CH2:22][N:23]2[CH2:27][CH2:26][O:25][C:24]2=[O:28])[CH:7]=1)[CH3:2]
Reactant: CS(=O)(=O)c1ccccc1B(O)O
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CN2CCOC2=O)c1
Product: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(-c3ccccc3S(C)(=O)=O)cc2CN2CCOC2=O)c1

Procedure:
Prepared according to the procedure described in Example 84, Step 1, using the following starting materials: {3-[4-bromo-2-(2-oxo-oxazolidin-3-ylmethyl)-phenoxy]-4-methoxy-phenyl}-acetic acid ethyl ester and 2-methylsulfonylphenylboronic acid.
Reaction SMILES: Cl[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[CH:9]=[O:10].C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[O:31][CH2:30][CH2:29][CH2:28]3)O1>C(COC)OC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[O:31]1[C:32]2[CH:33]=[CH:34][C:25]([C:2]3[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=3[CH:9]=[O:10])=[CH:26][C:27]=2[CH2:28][CH2:29][CH2:30]1
Reactant: Cc1nn(C)c(Cl)c1C=O
Reactant: CC1(C)OB(c2ccc3c(c2)CCCO3)OC1(C)C
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: Cc1nn(C)c(-c2ccc3c(c2)CCCO3)c1C=O
Temperature: 85 °C
Yield: 34.1 %

Procedure:
A solution of 5-chloro-1,3-dimethyl-1H-pyrazole-4-carboxaldehyde (200 mg, 1.26 mmol), sodium carbonate (282 mg, 2.66 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (426 mg, 1.64 mmol) and palladium tetrakis(triphenylphosphine) (73 mg, 0.063 mmol) in a mixture of dimethoxyethane (4 mL) and water (1.35 mL) was heated at 85° C. for 24 hours. After cooling to room temperature, the mixture was poured into water (10 mL). The aqueous layer was extracted with ethyl acetate (2×10 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20 then 50/50) to provide the desired product (27a) (110 mg, 0.43 mmol, 34%) as a beige solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:17]3[CH:16]=[CH:15][C:14]4[CH2:18][CH2:19][CH2:20][CH2:21][C:13]=4[C:12]=3[NH:11][C:10](=[O:22])[C:9]2=[O:23])[CH:5]=[CH:6][CH:7]=1.[C:24]1([S:30](Cl)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[O:22]=[C:10]1[NH:11][C:12]2[C:13]3[CH2:21][CH2:20][CH2:19][CH2:18][C:14]=3[CH:15]=[CH:16][C:17]=2[N:8]([C:4]2[CH:3]=[C:2]([NH:1][S:30]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:32])=[O:31])[CH:7]=[CH:6][CH:5]=2)[C:9]1=[O:23]
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Nc1cccc(-n2c(=O)c(=O)[nH]c3c4c(ccc32)CCCC4)c1
Product: O=c1[nH]c2c3c(ccc2n(-c2cccc(NS(=O)(=O)c4ccccc4)c2)c1=O)CCCC3
Yield: 54 %

Procedure:
4-(3-Aminophenyl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxaline-2,3-dione (50 mg, 0.145 mmol) and benzenesulfonyl chloride (38 mg, 0.218 mmol) were used in a process similar to Example 9 to give the titled compound (a white crystal, 35 mg, yield 54%).
Reaction SMILES: [C:1]([C:3]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:4]=1[NH2:5])#[N:2].[N:11]([O-])=O.[Na+].Cl>>[NH2:2][C:1]1[C:3]2[C:4](=[CH:6][CH:7]=[C:8]([F:10])[CH:9]=2)[NH:5][N:11]=1
Reactant: N#Cc1cc(F)ccc1N
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Product: Nc1n[nH]c2ccc(F)cc12

Procedure:
By the procedure of Example 2, 13.6 g. of 2-cyano-4-fluoroaniline is treated with 8.0 g. of sodium nitrite and concentrated hydrochloric acid, followed by stannous chloride to give 3-amino-5-fluoroindazole.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:5]2[C:10]=1[CH:9]=[N:8][C:7]([NH2:11])=[N:6]2.Br[C:23]1[CH:24]=[N:25][CH:26]=[C:27]([CH:33]=1)[C:28]([O:30][CH2:31][CH3:32])=[O:29].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC([O-])(C)C.[Na+]>O1CCOCC1.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]>[CH3:1][C:2]1[N:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:19])[F:20])[CH:13]=2)[N:5]2[C:10]=1[CH:9]=[N:8][C:7]([NH:11][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([CH:33]=1)[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:6]2
Reactant: CCOC(=O)c1cncc(Br)c1
Reactant: Cc1nc(-c2cccc(C(F)(F)F)c2)n2nc(N)ncc12
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: C1COCCO1
Product: CCOC(=O)c1cncc(Nc2ncc3c(C)nc(-c4cccc(C(F)(F)F)c4)n3n2)c1
Yield: 50.2 %

Procedure:
In a similar manner as described for Example 41, 5-methyl-7-[3-(trifluoromethyl)-phenyl]imidazo[5,1-f][1,2,4]triazin-2-amine (Intermediate 45) (0.025 g, 0.09 mmol), ethyl 5-bromonicotinate (0.020 g, 0.09 mmol), Pd2(dba)3 (0.008 g, 0.01 mmol), 2-(Di-t-butylphosphino)biphenyl (0.008 g, 0.03 mmol), and NaOtBu (0.011 g, 0.11 mmol) in 1,4-dioxane (1 mL) gave ethyl 5-({5-methyl-7-[3-(trifluoromethyl)phenyl]-imidazo[5,1-f][1,2,4]triazin-2-yl}amino)nicotinate (0.020 g) as a yellow solid. 1H NMR (Acetone-d6): δ9.24 (bs, 1H), 9.22 (s, 1H), 9.08 (d, J=2.4 Hz, 1H), 8.96-8.92 (m, 2H), 8.85 (d, J=1.4 Hz, 1H), 8.75 (s, 1H), 7.91-7.86 (m, 1H), 7.83-7.74 (m, 1H), 4.41 (q, J=7.1 Hz, 2H), 2.61 (s, 3H), 1.33 (t, J=7.1 Hz, 3H). MS m/z 443 (M+1).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:10].[OH:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(#N)C>[CH2:12]([NH:11][C:9](=[O:10])[CH2:8][N:26]1[CH2:27][CH2:28][N:23]([CH2:22][CH2:21][CH2:20][OH:19])[CH2:24][CH2:25]1)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: OCCCN1CCNCC1
Reactant: CCCCCCCNC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCCCCCCNC(=O)CN1CCN(CCCO)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 97.5 %

Procedure:
Potassium carbonate (2.49 g, 18 mmol) was added to a solution of 2-bromo-N-heptylacetamide (3.30 g, 15 mmol) obtained in Example 16 and 1-(3-hydroxypropyl)piperazine (2.16 g, 15 mmol) in acetonitrile (60 ml) and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution successively and dried over anhydrous sodium carbonate and the residue obtained after evaporation of the solvent was purified by a silica gel column chromatography (75 g of silica gel; developing solvent, ammonia-saturated methanol:chloroform=1:20) to provide 4.38 g (yield 97%) of N-heptyl-2-[4-[3-hydroxypropyl]piperazin-1-yl]acetamide as colorless oil.
Reaction SMILES: [CH3:1][C@@:2]12[O:9][C@@H:6]([CH:7]=[CH:8]1)[C:5](=[O:10])[CH2:4][C:3]2=[O:11].[H][H]>C(OCC)(=O)C.[Pd]>[CH3:1][C@@:2]12[O:9][C@@H:6]([CH2:7][CH2:8]1)[C:5](=[O:10])[CH2:4][C:3]2=[O:11]
Reactant: C[C@]12C=C[C@H](O1)C(=O)CC2=O
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: C[C@]12CC[C@H](O1)C(=O)CC2=O
Yield: 56.7 %

Procedure:
To a solution of (1R*,5S*)-1-methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4-dione (12.0 g, 0.079 mol) in ethyl acetate (100 ml) is added 10% palladium on carbon (2.4 g), followed by stirring under a 1 bar hydrogen atmosphere for 24 hours. The reaction mixture is then filtered through diatomaceous earth and concentrated to give a crude product which is purified by flash chromatography (hexane/ethyl acetate) to afford (1R*,5S*)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione (6.90 g) as pale yellow solid.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1B(O)O>>[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=1
Reactant: Cc1c2n(c3c(Br)cc(C#N)cc13)CCNC2=O
Reactant: OB(O)c1ccc(F)cc1F
Product: Cc1c2n(c3c(-c4ccc(F)cc4F)cc(C#N)cc13)CCNC2=O

Procedure:
The title compound, off-white solid (49 mg, 58%), MS (ISP) m/z=338.5 [(M+H)+], mp 237° C., was prepared in accordance with the general method of example 1 from 6-bromo-10-methyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-8-carbonitrile (intermediate 16) (76 mg, 0.25 mmol) and commercially available 2,4-difluoro-phenylboronic acid (51.3 mg, 0.325 mmol).
Reaction SMILES: [C:1]1([CH2:7][NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[C:13]([C:20]3[NH:28][C:27]4[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=4[CH:21]=3)[CH:14]=[CH:15][CH:16]=2)[N:11]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CS(C)=O>[CH2:7]([NH:8][C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[C:13]([C:20]3[NH:28][C:27]4[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=4[CH:21]=3)[CH:14]=[CH:15][CH:16]=2)[N:11]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NCc1ccccc1
Reactant: O=C1NCCc2[nH]c(-c3cccc4ccc(Cl)nc34)cc21
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: CS(C)=O
Product: O=C1NCCc2[nH]c(-c3cccc4ccc(NCc5ccccc5)nc34)cc21
Temperature: 100 °C
Yield: 8.9 %

Procedure:
Phenylmethanamine (0.144 g, 1.343 mmol) and 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.100 g, 0.336 mmol) were combined in 1 mL DMF, sealed, and heated to 100° C. overnight. The mixture was treated with TFA (0.104 ml, 1.343 mmol) and was diluted with 1 mL DMSO, filtered and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 5-60% ACN/H2O with 0.1% TFA); product-containing fractions were treated with saturated aq. NaHCO3 and DCM. The organic layer was separated and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-(benzylamino)-quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.011 g, 0.030 mmol, 9% yield) as a light-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.45 (1H, br. s), 7.88-8.01 (3H, m), 7.50 (1H, dt, J=7.7, 0.7 Hz), 7.39-7.45 (2H, m), 7.34 (2H, t, J=7.5 Hz), 7.21-7.28 (1H, m), 7.18 (1H, t, J=7.6 Hz), 6.88-7.00 (3H, m), 4.71 (2H, d, J=5.9 Hz), 3.34-3.38 (2H, m), 2.56-2.65 (2H, m). m/z (ESI, +ve) 369.0 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]4[CH:48]=[CH:47][C:28]([C:29]([NH:31][CH2:32][CH2:33][CH2:34][C:35]([NH:37][C@:38]5([C:44]([OH:46])=O)[CH2:40][C@H:39]5[CH:41]5[CH2:43][CH2:42]5)=[O:36])=[O:30])=[CH:27][CH:26]=4)[N:13]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:61][S:62]([NH2:65])(=[O:64])=[O:63].C1CCN2C(=NCCC2)CC1>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]4[CH:48]=[CH:47][C:28]([C:29]([NH:31][CH2:32][CH2:33][CH2:34][C:35]([NH:37][C@:38]5([C:44](=[O:46])[NH:65][S:62]([CH3:61])(=[O:64])=[O:63])[CH2:40][C@H:39]5[CH:41]5[CH2:42][CH2:43]5)=[O:36])=[O:30])=[CH:27][CH:26]=4)[N:13]=3)[CH2:9][CH2:10]2)=[CH:6][CH:7]=1
Reactant: O=C(CCCNC(=O)c1ccc(Nc2nc(NC3(c4ccc(Cl)cc4)CC3)nc(OCC(F)(F)F)n2)cc1)N[C@]1(C(=O)O)C[C@H]1C1CC1
Reactant: CS(N)(=O)=O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: CS(=O)(=O)NC(=O)[C@@]1(NC(=O)CCCNC(=O)c2ccc(Nc3nc(NC4(c5ccc(Cl)cc5)CC4)nc(OCC(F)(F)F)n3)cc2)C[C@H]1C1CC1
Temperature: 65 °C
Reaction time: 16 h
Yield: 43.8 %

Procedure:
To a solution of (1S,2R)-2-(4-(4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzamido)butanamido)bi(cyclopropane)-2-carboxylic acid (15 mg, 0.02 mmol) in THF solution was added CDI (7.0 mg, 0.04 mmol). The mixture was heated at 65° C. for 1 hour. After cooling to room temperature, methanesulfonamide (4.2 mg, 0.04 mmol) and DBU (9.9 ul, 0.07 mmol) were added to the mixture. The reaction mixture was stirred at r.t. for 16 hours. The solvent was evaporated and the residue was purified by preparative HPLC to afford 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(4-((1S,2R)-2-(methylsulfonylcarbamoyl)bi(cyclopropan)-2-ylamino)-4-oxobutyl)benzamide (6.7 mg, 40%) as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 0.34 (m, 2H), 0.57 (q, J=9.20 Hz, 2H), 0.71-0.80 (m, 1H), 1.08-1.13 (m, 1H), 1.18 (ddd, J=9.41, 7.53, 7.40 Hz, 1H), 1.34-1.45 (m, 4H), 1.77 (dd, J=7.53, 5.02 Hz, 1H), 1.85-1.97 (m, 1H), 2.26-2.36 (m, 2H), 2.37 (m, 2H), 3.26 (s, 3H), 3.41-3.51 (m, 1H), 4.00 (s, 2H), 7.23-7.33 (m, 4H), 7.60-7.75 (m, 3H), 7.85 (m, 1H); LC-MS (Condition A), MS m/z 765.1 (M++H).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30](Br)[N:29]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Cl:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([C:40]5[CH:39]=[CH:38][CH:37]=[C:36]([Cl:35])[CH:41]=5)[N:29]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: OB(O)c1cccc(Cl)c1
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(Br)n4)cc3)cc2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(-c5cccc(Cl)c5)n4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 10, using 1-{4′-[4-(6-bromo-pyridin-2-ylamino)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester and 3-chlorophenylboronic acid. (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) was used in place of tetrakis(triphenylphosphine)palladium(0).
Reaction SMILES: [OH-].[K+].[Cl:3][C:4]1[C:12]([Cl:13])=[CH:11][C:10]([Cl:14])=[C:9]2[C:5]=1[C:6]([CH2:15][C:16]([O:18]C)=[O:17])=[CH:7][NH:8]2>O.CO>[Cl:3][C:4]1[C:12]([Cl:13])=[CH:11][C:10]([Cl:14])=[C:9]2[C:5]=1[C:6]([CH2:15][C:16]([OH:18])=[O:17])=[CH:7][NH:8]2
Reactant: COC(=O)Cc1c[nH]c2c(Cl)cc(Cl)c(Cl)c12
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)Cc1c[nH]c2c(Cl)cc(Cl)c(Cl)c12
Temperature: 50 °C

Procedure:
An aqueous solution containing 8.4 g (0.15 mole) of potassium hydroxide in 10 ml of water was added to a solution of 4.3 g (0.015 mole) of methyl 4,5,7-trichloroindole-3-acetate in 50 ml of methanol, and the resulting mixture was heated at 50° C. for 10 hours, after which the reaction mixture was concentrated under reduced pressure until it became an aqueous solution. Said aqueous solution was acidified with acetic acid and extracted with ethyl acetate. The ethyl acetate phase was washed with water and a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate, and subsequently the ethyl acetate was removed by distillation under reduced pressure to obtain crude 4,5,7-trichloroindole-3-acetic acid, which was then purified by a column chromatography (silica gel) to obtain 3.3. g of the desired compound represented by the formula: ##STR16##
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[NH:20][C:19](=[O:21])[C:18]([C:22]#[N:23])=[C:17]([S:24]([CH3:26])=[O:25])[CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:28][C:29]([NH2:31])=[O:30].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[N:20]=[C:19]([O:21][CH2:28][C:29]([NH2:31])=[O:30])[C:18]([C:22]#[N:23])=[C:17]([S:24]([CH3:26])=[O:25])[CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC(=O)CBr
Reactant: CS(=O)c1cc(-c2ccccc2OCc2ccccc2)[nH]c(=O)c1C#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CS(=O)c1cc(-c2ccccc2OCc2ccccc2)nc(OCC(N)=O)c1C#N
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 60.8 %

Procedure:
A mixture of 6-[2-(benzyloxy)phenyl]-4-(methylsulfinyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (2.97 g, 8.16 mmol), bromoacetamide (1.27 g, 9.21 mmol), and K2CO3 (1.43 g, 10.4 mmol) in DMF (30 mL) was stirred at 60° C. for 1.5 hrs. The reaction mixture was poured into water, and the resulting precipitates were collected by filtration. The solid obtained was washed with acetone to give 2-{[6-[2-(benzyloxy)phenyl]-3-cyano-4-(methylsulfinyl)-2-pyridinyl]oxy}acetamide as a solid (2.09 g, yield; 61%).
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[OH-].[Ca+2:22].[OH-]>C(O)(=O)C>[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Ca+2:22].[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: [Ca+2]
Agent: [OH-]
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCCCCCC(=O)[O-]
Reaction time: 0.58 h

Procedure:
73.7 g of stearic acid, 76.2 g PbO and 3.6 g calcium hydroxide were stirred at 40° to 45° C. and 1% of 50% acetic acid added. The temperature rose to approximately 70° C. The total stirring time was 35 minutes. A pale yellowish powder having a melting temperature of 58° to more than 250° C., a lead content of 46.1%, a calcium content of 1.2%, and an acid value of 3.1 was obtained.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][S:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl.C(N=C=N)C.[O:27]=[C:28]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[N:30][N:29]1[CH2:38][CH2:39][CH2:40][C:41](O)=[O:42]>ClCCl.CN(C)C1C=CN=CC=1.O>[CH2:1]([C@H:8]1[CH2:12][S:11][C:10](=[O:13])[N:9]1[C:41](=[O:42])[CH2:40][CH2:39][CH2:38][N:29]1[C:28](=[O:27])[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[N:30]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1N[C@@H](Cc2ccccc2)CS1
Reactant: O=C(O)CCCn1nnc2ccccc2c1=O
Agent: CCN=C=N
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: O=C(CCCn1nnc2ccccc2c1=O)N1C(=O)SC[C@@H]1Cc1ccccc1
Reaction time: 0.17 h

Procedure:
To a solution of the compound obtained from step c above (2.1 g) in dichloromethane (25 mL) cooled to 0° C., 4-dimethylaminopridine (0.334 g) and triethylamine (5.7 mL) were added. After stirring the reaction mixture for 10 minutes, 1-β-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (3.9 g) and 4-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)butanoic acid (3 g) were added, and the reaction mixture was stirred at room temperature for 14 hours. Dichloromethane and water were added to the reaction mixture. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 25% ethyl acetate in hexane as eluant to afford the title compound (4.4 g). Mass (m/z): 409.16
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]1([CH3:17])[C:8]([CH3:9])=[CH:7][CH2:6][CH:5]1[CH:10]([CH2:13][C:14]([CH3:16])=[CH2:15])[CH:11]=[O:12]>C(O)C>[CH3:3][C:4]1([CH3:17])[C:8]([CH3:9])=[CH:7][CH2:6][CH:5]1[CH:10]([CH2:13][C:14]([CH3:16])=[CH2:15])[CH2:11][OH:12]
Reactant: C=C(C)CC(C=O)C1CC=C(C)C1(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: C=C(C)CC(CO)C1CC=C(C)C1(C)C
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 63.7 %

Procedure:
A 500 ml 3 neck flask was charged with 250 ml of ethanol and 6.0 g of sodium borohydride (0.16 mole). To the flask maintained at 0° C. in an ice bath was added dropwise 74.6 g of the aldehyde from example 1 at a purity of 84.3% (0.30 mole) in 100 ml of ethanol. The batch was stirred 45 minutes at 0° C. The reaction was now quenched by the addition of 50 ml of 25% hydrochloric acid at 0°-5° C. The mixture was poured onto 300 ml of brine and extracted with 3×100 ml of hexane. The hexane was washed with 2×250 ml of brine, dried with magnesium sulfate, filtered, and concentrated in vacuo. The batch was distilled through a 10 cm vigreaux column to afford 48 g of purified product (58% yield). BP 78° C./0.25 mmHg; 1H-NMR (300 MHz), δ0.91 (3H, s), 1.09 (3H, s), 1.60 (3H, s), 1.77 (3H, s), 1.85-2.30 (7H, m), 3.66 (2H, m), 4.80 (2H, s), 5.24 (1H, s); 13C-NMR (75 MHz), δ12.90, 20.20, 22.76, 27.36, 34.07, 39.57, 40.61, 47.53, 50.32, 64.52, 112.63, 122.26, 146.38, 149.32; IR (Neat), 3370, 2960, 2940, 1650, 1040 cm-1 ; MS (m/e), 208 (M+), 95 (Base).
Reaction SMILES: [CH3:1][O:2][C@@H:3]1[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[C:21]2[N:20]=[C:18]([NH2:19])[NH:17][C:15](=[O:16])[C:14]=2[N:13]=[CH:12]1.C[Si](Cl)(C)C.[C:27](Cl)(=[O:31])[CH:28]([CH3:30])[CH3:29].[NH4+].[OH-]>N1C=CC=CC=1.O>[C:27]([NH:19][C:18]1[NH:17][C:15](=[O:16])[C:14]2[N:13]=[CH:12][N:11]([C:21]=2[N:20]=1)[C@@H:4]1[O:5][C@H:6]([CH2:9][OH:10])[C@@H:7]([OH:8])[C@H:3]1[O:2][CH3:1])(=[O:31])[CH:28]([CH3:30])[CH3:29]
Reactant: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(=O)[nH]c(N)nc21
Reactant: CC(C)C(=O)Cl
Agent: C[Si](C)(C)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: c1ccncc1
Product: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(=O)[nH]c(NC(=O)C(C)C)nc21
Reaction time: 0.33 h

Procedure:
2'-O-methylguanosine (3.5 g) in pyridine (100 ml) was treated with trimethylsilyl chloride (9 ml, 6 eq) and isobutyryl chloride (6.2 ml) at RT for 4 hr. The reaction mixture was cooled in an ice bath, H2O (20 ml) was added and stirring continued for an additional 20 min. NH4OH (20 ml) was added and after stirring for 30 min the reaction mixture was evaporated. The residue was triturated with H2O, filtered and the filtrate evaporated and purified by silica gel chromatography as per the procedure of Example 4 to yield the product as an off white solid (1.5 g). 1H NMR (DMSO-d6) δ 1.1 [d, 6, CH(CH3)2 ], 2.77 [m, 1, CH(CH3)2 ], 3.33-3.6 (m, 5, OCH3, H-5'), 3.93 (m, 1, H-4'), 4.22 (m, 1), 4.3 (m, 1), 5.1 (t, 1, 5'-OH), 5.28 (d, 1, 3'-OH), 5.9 (d, 1, H-1'), 8.28 (s, 1, H-8) and 11.9 (br s, 1, NH).
Reaction SMILES: [CH2:1]([Si:9]([CH3:12])([CH3:11])Cl)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH3:13][C:14]([CH3:25])([C:16](=[O:24])[CH2:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH3:15].C(N(CC)CC)C>C(OCC)C>[CH2:1]([Si:9]([CH3:12])([CH3:11])[O:24][C:16](=[CH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:14]([CH3:13])([CH3:15])[CH3:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CC(C)(C)C(=O)CC(=O)C(C)(C)C
Reactant: CCCCCCCC[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CCCCCCCC[Si](C)(C)OC(=CC(=O)C(C)(C)C)C(C)(C)C

Procedure:
A dehydrating compound was prepared by the dropwise addition of octyldimethylchlorosilane to an equal molar solution of 2,2,6,6-tetramethyl-3,5-heptanedione and triethylamine in ethyl ether. The mixture was heated until it refluxed for a period of 6 hours, and filtered to remove salts. The solvent was removed under reduced pressure to yield 3-(octyldimethylsiloxy)-2,2,6,6-tetramethylhept-3-ene-5-one.