Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].C(OP([CH2:11][C:12]#[N:13])(=O)OCC)C.[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]([C:31](=O)[CH3:32])[CH:29]=3)[C:24]([CH3:35])([CH3:34])[CH2:23][CH:22]=2)=[CH:17][CH:16]=1>C1COCC1.CCOCC>[CH3:34][C:24]1([CH3:35])[CH2:23][CH:22]=[C:21]([C:18]2[CH:17]=[CH:16][C:15]([CH3:14])=[CH:20][CH:19]=2)[C:30]2[CH:29]=[C:28](/[C:31](/[CH3:32])=[CH:11]/[C:12]#[N:13])[CH:27]=[CH:26][C:25]1=2
Reactant: CC(=O)c1ccc2c(c1)C(c1ccc(C)cc1)=CCC2(C)C
Reactant: CCOP(=O)(CC#N)OCC
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: C/C(=C\C#N)c1ccc2c(c1)C(c1ccc(C)cc1)=CCC2(C)C
Reaction time: 0.67 h

Procedure:
To a slurry of NaH (48.0 mg, 2.00 mmol) in THF (6 ml), was added diethylcyanomethylphosphonate (450.0 mg, 2.50 mmol). After 40 mins, a solution of 3,4-dihydro-1-(4-methylphenyl)-4,4-dimethyl-7-acetylnaphthalene (Compound V) 95.0 mg, (0.33 mmol) in THF (4 ml) was added. The mixture was stirred for 16 hours, diluted with ether (100 ml), and washed with water, and saturated aqueous NaCl before being dried over MgSO4. Removal of the solvents under reduced pressure, and column chromatography (3% EtOAc/hexanes) afforded the title compound as a solid. 1H NMR (CDCl3): δ 7.39 (1H, d, J=1H), 7.32 (1H, dd, J=2.0, 8.1Hz), 7.20-7.25 (4H, brs), 7.15 (1H, d, J=2.0 Hz), 6.03 (1H, t, J=6.0 Hz), 5.44 (1H, s), 2.42 (3H, s), 2.36 (2H, d, J=6.0 Hz), 2.35 (3H, s), 1.35 (6H, s).
Reaction SMILES: F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[C:13]1[C:14]2[CH:23]=[CH:22][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:15]=2[C:16](=[O:20])[N:17]([CH3:19])[CH:18]=1.[CH:34]1([NH2:39])[CH2:38][CH2:37][CH2:36][CH2:35]1.C(N(CC)CC)C>CS(C)=O>[CH:34]1([NH:39][C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=2[C:13]2[C:14]3[CH:23]=[CH:22][NH:21][C:15]=3[C:16](=[O:20])[N:17]([CH3:19])[CH:18]=2)[CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: CCOC(=O)c1ccc(F)c(-c2cn(C)c(=O)c3c2ccn3S(=O)(=O)c2ccc(C)cc2)c1
Reactant: NC1CCCC1
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CCOC(=O)c1ccc(NC2CCCC2)c(-c2cn(C)c(=O)c3[nH]ccc23)c1
Yield: 25 %

Procedure:
A mixture of Example 9a (0.094 g, 0.2 mmol), cyclopentanamine (0.034 g, 0.4 mmol), and triethylamine (0.081 g, 0.8 mmol) in DMSO (2 mL) was heated at 120° C. overnight. The reaction mixture was purified by preparative HPLC (C18, 10-80% acetonitrile in 0.1% TFA/water to afford 0.019 g of the title product. 1H NMR (500 MHz, DMSO-d6) δ 1.27 (t, J=7.02 Hz, 3H), 1.32-1.36 (m, 2H), 1.47-1.55 (m, 3H), 1.88-1.93 (m, 2H), 3.55 (s, 3H), 3.83-3.88 (m, 1H), 4.22 (q, J=7.02 Hz, 2H), 5.94 (t, J=2.29 Hz, 1H), 6.77 (d, J=8.85 Hz, 1H), 7.22 (s, 1H), 7.28 (t, J=2.75 Hz, 1H), 7.63 (d, J=1.83 Hz, 1H), 7.82 (dd, J=8.54, 2.14, 1H), 12.01 (s, 1H). MS (ESI+) m/z 380.2 (M+H)+.
Reaction SMILES: Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][C:3]=1[C:8]1[CH:13]=[C:12]([C:14]#[N:15])[CH:11]=[CH:10][N:9]=1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:22]=1[Cl:23]>>[Cl:16][C:17]1[CH:18]=[C:19]([C:2]2[N:6]([CH3:7])[CH:5]=[N:4][C:3]=2[C:8]2[CH:13]=[C:12]([C:14]#[N:15])[CH:11]=[CH:10][N:9]=2)[CH:20]=[CH:21][C:22]=1[Cl:23]
Reactant: Cn1cnc(-c2cc(C#N)ccn2)c1Br
Reactant: OB(O)c1ccc(Cl)c(Cl)c1
Product: Cn1cnc(-c2cc(C#N)ccn2)c1-c1ccc(Cl)c(Cl)c1

Procedure:
The title compound was prepared from 2-(5-bromo-1-methyl-1H-imidazol-4-yl)pyridine-4-carbonitrile and 3,4-dichlorophenylboronic acid according to the procedure for the preparation of Example 3, part A. [M+H] Calc'd for C16H10Cl2N4, 330. Found, 329, 331.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2([OH:19])[CH2:11][N:10]([C:12](OC(C)(C)C)=O)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.FC(F)(F)C(O)=O.ClCCl.C(N(CC)CC)C.ClC1[N:47]=[CH:46][C:45]([Cl:48])=[CH:44][C:39]=1[C:40]([O:42][CH3:43])=[O:41]>ClCCl.O1CCCC1.CO>[Cl:48][C:45]1[CH:46]=[N:47][C:12]([N:10]2[CH2:9][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)([OH:19])[CH2:11]2)=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41]
Reactant: COC(=O)c1cc(Cl)cnc1Cl
Reactant: CC(C)(C)OC(=O)N1CC(O)(c2cccc(F)c2)C1
Solvent: C1CCOC1
Solvent: CO
Solvent: ClCCl
Product: COC(=O)c1cc(Cl)cnc1N1CC(O)(c2cccc(F)c2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 56.7 %

Procedure:
To a cooled (0° C.) solution of tert-butyl 3-(3-fluorophenyl)-3-hydroxyazetidine-1-carboxylate (D28) (100 mg, 0.374 mmol) in dichloromethane (0.5 ml), a mixture 3:1 of trifluoroacetic acid/dichloromethane (1 ml) was added and the mixture was stirred 30 min at room temperature. The residue obtained after solvent evaporation was dissolved in a mixture 3:1 of tetrahydrofuran/methanol (1 ml) and triethylamine (0.156 ml, 1.122 mmol) was added followed by addition of methyl 2,5-dichloronicotinate (77.32 mg, 0.374 mmol). The resulting mixture was heated 15 h at 60° C. After solvent evaporation the residue was taken in NH4Cl sat. sol. (10 ml) and the resulting mixture was extracted with ethylacetate (2×10 ml). The residue obtained after solvet evaporation was purified by SPE-Si cartridge (5 g) eluting with a mixture cyclohexane/ethylacetate from 100/0 to 90:10. Collected fractions, after solvent evaporation afforded the title compound (D80) (71.4 mg)
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]/OC.Cl.Cl.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH2:27])=[CH:22][C:21]=1[OH:28].C(N(CC)CC)C>CN(C)C=O>[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH:27]/[CH:14]=[C:5]2\[C:6](=[O:13])[NH:7][C:8](=[O:12])[C:9]3[C:4]\2=[CH:3][C:2]([I:1])=[CH:11][CH:10]=3)=[CH:22][C:21]=1[OH:28]
Reactant: NCc1ccc(N)c(O)c1
Reactant: CO/C=C1/C(=O)NC(=O)c2ccc(I)cc21
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Nc1ccc(CN/C=C2\C(=O)NC(=O)c3ccc(I)cc32)cc1O
Temperature: 25 °C
Reaction time: 60 h
Yield: 99.6 %

Procedure:
To a suspension of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (1.0 g, 3.0 mmol) and 2-amino-5-(aminomethyl)phenol dihydrochloride (0.64 g, 3.0 mmol) in N,N-dimethylformamide (15 mL) is added triethylamine (1.2 mL, 9.0 mmol). The mixture is stirred at room temperature for 60 hours and then concentrated to dryness under reduced pressure. The residue is then triturated with water, and the solid is collected by filtration, washed successively with diethyl ether and acetonitrile, and dried under house vacuum to provide (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione as a golden powder (1.3 g, 100%).
Reaction SMILES: Cl[C:2]1[N:21]=[C:5]2[C:6]([NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([S:17]([CH3:20])(=[O:19])=[O:18])[CH:12]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:30]=[C:31]([CH:33]=[CH:34][CH:35]=2)[NH2:32])[CH2:25][CH2:24]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:20][S:17]([C:13]1[CH:12]=[C:11]([NH:10][C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:32][C:31]4[CH:33]=[CH:34][CH:35]=[C:29]([N:26]5[CH2:25][CH2:24][N:23]([CH3:22])[CH2:28][CH2:27]5)[CH:30]=4)[N:21]=3)[CH:9]=[CH:8][CH:7]=2)[CH:16]=[CH:15][CH:14]=1)(=[O:19])=[O:18]
Reactant: CS(=O)(=O)c1cccc(Nc2cccn3nc(Cl)nc23)c1
Reactant: CN1CCN(c2cccc(N)c2)CC1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCN(c2cccc(Nc3nc4c(Nc5cccc(S(C)(=O)=O)c5)cccn4n3)c2)CC1

Procedure:
N(8)-(3-Methanesulfonyl-phenyl)-N(2)-[3-(4-methyl-piperazin-1-yl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine was prepared from (2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-(3-methanesulfonyl-phenyl)-amine (75.0 mg, 0.232 mmol) and 3-(4-methylpiperazin-1-yl)aniline (50.0 mg, 0.261 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.013 g, 12%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.05 (d, J=6.1 Hz, 1H), 7.81 (s, 1H), 7.60-7.50 (m, 2H), 7.45 (d, J=7.3 Hz, 1H), 7.27-7.18 (m, 3H), 7.09 (d, J=7.3 Hz, 1H), 6.85 (s, 1H), 6.81 (t, J=7.1 Hz, 1H), 6.75 (s, 1H), 6.60 (d, J=8.3 Hz, 1H), 3.30-3.25 (m, 4H), 3.08 (s, 3H), 2.62-2.57 (m, 4H), 2.37 (s, 3H). MS=478 (MH)+.
Reaction SMILES: CN([CH:4]=[C:5]1[CH2:11][C:10](=[O:12])[NH:9][C:8]2[CH:13]=[CH:14][C:15]([I:17])=[CH:16][C:7]=2[C:6]1=O)C.C([O-])([O-])=O.[K+].[K+].[CH3:25][O:26][C:27]1[CH:28]=[C:29]([NH:35][C:36]([NH2:38])=[NH:37])[CH:30]=[CH:31][C:32]=1[O:33][CH3:34].Cl>CCO.O>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([NH:35][C:36]2[N:38]=[CH:4][C:5]3[CH2:11][C:10](=[O:12])[NH:9][C:8]4[CH:13]=[CH:14][C:15]([I:17])=[CH:16][C:7]=4[C:6]=3[N:37]=2)[CH:30]=[CH:31][C:32]=1[O:33][CH3:34]
Reactant: CN(C)C=C1CC(=O)Nc2ccc(I)cc2C1=O
Reactant: COc1ccc(NC(=N)N)cc1OC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: COc1ccc(Nc2ncc3c(n2)-c2cc(I)ccc2NC(=O)C3)cc1OC
Temperature: 80 °C

Procedure:
To a solution of 4-dimethylaminomethylene-7-iodo-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (v-a) (1.64 g, 4.6 mmol) in 50 mL EtOH was added K2CO3 (1.82 g, 11.04 mmol) and 1-(3,4-dimethoxyphenyl)guanidine (1.31 g, 5.06 mmol), and the reaction was heated to 80° C. for 12 h. The reaction was then cooled to 22° C., diluted with H2O, and treated with 1 M HCl to pH 3. The resulting solid was filtered and washed with H2O, followed by EtOH and Et2O. The crude product was dried in vacuo to give I-26 (1.8 g, 81%): HRMS Calcd. for C20H17IN4O3: 489.0423, Found 489.0431.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]1[C:16](=[O:17])[C:15]([CH3:18])=[C:14](Br)[C:13]1=[O:20].[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[F-].[Cs+]>[Cl-].C([N+](CC)(CC1C=CC=CC=1)CC)C.C1(C)C=CC=CC=1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]1[C:13](=[O:20])[C:14]([C:26]2[CH:27]=[CH:28][C:23]([C:22]([F:33])([F:32])[F:21])=[CH:24][CH:25]=2)=[C:15]([CH3:18])[C:16]1=[O:17]
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: COc1ccc(CN2C(=O)C(C)=C(Br)C2=O)c(OC)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(CN2C(=O)C(C)=C(c3ccc(C(F)(F)F)cc3)C2=O)c(OC)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 115.7 %

Procedure:
{[2,4-bis(methyloxy)phenyl]methyl}-3-bromo-4-methyl-1H-pyrrole-2,5-dione (P9, 3.3, 9.7 mmol), [4-(trifluoromethyl)phenyl]boronic acid (3.68 g, 19.40 mmol), bis(triphenylphosphine)palladium(ii) chloride (0.601 g, 0.91 mmol) and cesium fluoride (3.98 g, 26.2 mmol) and N,N-diethyl-N-(phenylmethyl)ethanaminium chloride (0.22 g, 0.970 mmol) were dissolved in Toluene (60 mL)/Water (60.0 mL) and the reaction mixture was stirred at 90° C. overnight. Toluene was evaporated under reduced pressure and a saturated solution of NH4Cl was added. The aqueous phase was extracted with DCM, solvent was eliminated under reduced pressure and crude product by flash chromatography (Biotage SiO2, eluent: Cy/AcOEt 98:2; fraction volume: 45 mL) affording 1-{[2,4-bis(methyloxy)phenyl]methyl}-3-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione (P10, 4.55 g, 11.22 mmol)
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:19])[CH:7]=O)[CH3:2].[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH2:30][C:31]#[N:32])[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]>>[CH3:20][O:21][C:22]1[CH:23]=[C:24](/[C:30](=[CH:7]/[C:6]2[CH:9]=[CH:10][C:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:19])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)/[C:31]#[N:32])[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]
Reactant: COc1ccc(CC#N)cc1OC
Reactant: CCOc1cc(C=O)ccc1OCCCCCCO
Product: CCOc1cc(/C=C(\C#N)c2ccc(OC)c(OC)c2)ccc1OCCCCCCO
Yield: 96 %

Procedure:
(2Z)-2-(3,4-dimethoxyphenyl)-3-{3-ethoxy-4-[(6-hydroxyhexyl)oxy]phenyl}prop-2-enenitrile is prepared starting from 3-ethoxy-4-[(6-hydroxyhexyl)oxy]benzaldehyde and (3,4-dimethoxyphenyl)acetonitrile according the same procedure following for example 10 in 96% yield. This material proves chromatographically homogenous and displays spectral characteristics consistent with its assigned structure.
Reaction SMILES: C[C:2]1[CH:10]=[C:9](/[CH:11]=[CH:12]/[C:13]2[C:22]([CH2:23][N:24]3[CH:28]=[CH:27][CH:26]=[N:25]3)=[CH:21][C:20]3[C:19]([CH3:30])([CH3:29])[C:18](=[O:31])[CH2:17][C:16]([CH3:33])([CH3:32])[C:15]=3[CH:14]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]>CO.[Li+].[OH-]>[CH3:29][C:19]1([CH3:30])[C:18](=[O:31])[CH2:17][C:16]([CH3:32])([CH3:33])[C:15]2[CH:14]=[C:13](/[CH:12]=[CH:11]/[C:9]3[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[CH:2][CH:10]=3)[C:22]([CH2:23][N:24]3[CH:28]=[CH:27][CH:26]=[N:25]3)=[CH:21][C:20]1=2
Reactant: Cc1cc(/C=C/c2cc3c(cc2Cn2cccn2)C(C)(C)C(=O)CC3(C)C)ccc1C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: CC1(C)CC(=O)C(C)(C)c2cc(Cn3cccn3)c(/C=C/c3ccc(C(=O)O)cc3)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 14.8 %

Procedure:
A mixture of 0.7 g (1.58 mmol) of methyl-4-[(E)-2-(5,5,8,8-tetramethyl-3-pyrazol-1-ylmethyl-6-oxo -5,6,7,8-tetrahydro-naphthalen-2-yl)vinyl]-benzoic acid in 40 ml of MeOH and 20 ml of 1 N LiOH was heated to reflux temperature. After 1 h, the reaction was cooled to room temperature and the MeOH removed under reduced pressure. The aqueous solution was acidified with 2 N HCl, extracted with ethyl acetate, washed with brine, dried over sodium sulfate and adsorbed onto silica gel. The product was purified by flash chromatography (gradient elution: 10-30% ethyl acetate/hexane with 0.2% acetic acid) and by recrystallization (ethyl acetate/hexane) to afford 100 mg (15%) of 4-[(E)-2-(5,5,8,8-tetramethyl-3-pyrazol-1-ylmethyl-6-oxo -5,6,7,8-tetrahydro-naphthalen-2-yl)vinyl]-benzoic acid (mp=233-233.5) 133.
Reaction SMILES: [N:1]1[C:10]2[NH:9][C:8]3[CH:11]=[C:12]([CH2:15][C:16]([NH2:18])=[S:17])[CH:13]=[CH:14][C:7]=3[S:6][C:5]=2[N:4]=[CH:3][CH:2]=1.C(O)C.Br.Br[CH2:24][C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)=O.C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C=O>[N:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:25]1[N:18]=[C:16]([CH2:15][C:12]2[CH:13]=[CH:14][C:7]3[S:6][C:5]4[N:4]=[CH:3][CH:2]=[N:1][C:10]=4[NH:9][C:8]=3[CH:11]=2)[S:17][CH:24]=1
Reactant: O=C(CBr)c1ccccn1
Reactant: NC(=S)Cc1ccc2c(c1)Nc1nccnc1S2
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCO
Solvent: ClCCl
Product: c1ccc(-c2csc(Cc3ccc4c(c3)Nc3nccnc3S4)n2)nc1
Temperature: 65 °C
Yield: 56.1 %

Procedure:
To a solution of 550 mg of (10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)thioacetamide in a solvent mixture of ethanol (10 ml) with N,N-dimethylformamide (10 ml) was added 560 mg of (2-bromoacetyl)pyridine hydrobromide and the resulting mixture was heated to 60 to 70° C. for 2 hours. Then the reaction mixture was brought back to room temperature and distributed into dichloromethane and an aqueous solution of sodium bicarbonate. After extracting the organic layer, the extract was washed with water and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the crystals thus precipitated were washed successively with ethyl acetate and diethyl ether to thereby give 420 mg of the title compound as yellow crystals.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:9]=[C:10]([CH:14]([N:18]3[CH:22]=[C:21]([C:23]4[C:24]5[CH:31]=[CH:30][N:29](COCC[Si](C)(C)C)[C:25]=5[N:26]=[CH:27][N:28]=4)[CH:20]=[N:19]3)[CH2:15][C:16]#[N:17])[CH:11]=[N:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)Cl.[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44].CO.C(N)CN>>[F:46][C:45]([F:48])([F:47])[C:43]([OH:49])=[O:44].[C:1]1([S:7][C:8]2[CH:9]=[C:10]([CH:14]([N:18]3[CH:22]=[C:21]([C:23]4[C:24]5[CH:31]=[CH:30][NH:29][C:25]=5[N:26]=[CH:27][N:28]=4)[CH:20]=[N:19]3)[CH2:15][C:16]#[N:17])[CH:11]=[N:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(C(CC#N)c4cncc(Sc5ccccc5)c4)c3)ncnc21
Solvent: O=C(O)C(F)(F)F
Solvent: NCCN
Solvent: ClCCl
Product: N#CCC(c1cncc(Sc2ccccc2)c1)n1cc(-c2ncnc3[nH]ccc23)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 58 %

Procedure:
The 3-[5-(phenylthio)pyridin-3-yl]-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (0.110 g, 0.000199 mol) was dissolved in DCM (5.0 mL, 0.078 mol) and TFA (2.0 mL, 0.026 mol), and the mixture was stirred at room temperature for 1 hour. The solvent was removed in vacuo, and the resulting residue was dissolved in methanol (5.0 mL, 0.12 mol), and ethylenediamine (0.1 mL, 0.002 mol) was added. This reaction mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo, and the crude product was purified by LCMS (pH=2) to yield the title compound as an amorphous solid (62 mg, 58.07%). 1H NMR (400 MHz, DMSO): δ □12.80 (s), 9.10 (s) 8.87 (d), 8.60 (s), 8.50 (s), 8.43 (s), 7.82 (s), 7.78 (m), 7.39 (m), 7.25 (m), 7.18 (d), 6.20 (m), 3.84 (m), 3.70 (m). LC/MS (M+H)F: m/z=424.15
Reaction SMILES: [NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O=[C:29]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:30]([O:32][CH2:33][CH3:34])=[O:31]>>[C:14]([O:13][C:11]([CH2:10][N:7]1[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH:3]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:2]([NH:1][CH:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:8]1=[O:9])=[O:12])([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OC(=O)CN1C(=O)C(N)C(c2ccccc2)Sc2ccccc21
Reactant: CCCCCCCCC(=O)C(=O)OCC
Product: CCCCCCCCC(NC1C(=O)N(CC(=O)OC(C)(C)C)c2ccccc2SC1c1ccccc1)C(=O)OCC
Yield: 78 %

Procedure:
1.1 g of the compound obtained in Example 20 was reacted with 3.0 g of ethyl 2-ketodecanoate in the same manner as described in Example 21. The reaction product was fractionated and purified by silica gel column chromatography using a 9:1 mixture of benzene and ethyl acetate as the eluent. Thus, there was obtained 1.3 g of the desired compound in the form of an oily material.
Reaction SMILES: C(NC1CC2C(=CC=C(NC(C3C(C4C=CC(F)=CC=4)=CC=CC=3)=O)C=2)C1)(=O)C.Br[C:31]1[CH:48]=[CH:47][C:46]([N+:49]([O-:51])=[O:50])=[CH:45][C:32]=1[C:33]([NH:35][C:36]1[CH:37]=[C:38]2[C:42](=[CH:43][CH:44]=1)[CH2:41][CH2:40][CH2:39]2)=[O:34].[S:52]1[CH:56]=[CH:55][CH:54]=[C:53]1B(O)O>>[CH2:41]1[C:42]2[C:38](=[CH:37][C:36]([NH:35][C:33](=[O:34])[C:32]3[CH:45]=[C:46]([N+:49]([O-:51])=[O:50])[CH:47]=[CH:48][C:31]=3[C:53]3[S:52][CH:56]=[CH:55][CH:54]=3)=[CH:44][CH:43]=2)[CH2:39][CH2:40]1
Reactant: O=C(Nc1ccc2c(c1)CCC2)c1cc([N+](=O)[O-])ccc1Br
Reactant: OB(O)c1cccs1
Agent: CC(=O)NC1Cc2ccc(NC(=O)c3ccccc3-c3ccc(F)cc3)cc2C1
Product: O=C(Nc1ccc2c(c1)CCC2)c1cc([N+](=O)[O-])ccc1-c1cccs1

Procedure:
N-(Indan-5-yl)-5-nitro-2-(thiophen-2-yl)-benzamide is prepared similarly to the title compound of Example 3 using the title B compound, 2-bromo-N-(indan-5-yl)-5-nitro-benzamide (0.137 g, 0.380 mmol) and 2-thiopheneboronic acid (0.073 9, 0.570 mmol). 1H NMR (DMSO-d6, 300 MHz): δ 10.59 (1H, s), 8.38 (1H, dd), 8.30 (1H, d), 7.81 (1H, d), 7.73 (1H, d), 7.06 (1H, s), 7.46 (1H, d), 7.30 (1H, d), 7.18 (2H, m), 2.83 (4H, q), 2.01 (2H, m).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])[C:8]([O:29][CH3:30])=[C:9]([NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]([CH3:28])=[C:18]([N:20]3[CH:24]=[C:23]([C:25](O)=[O:26])[N:22]=[CH:21]3)[CH:19]=2)=[O:13])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:36]([NH2:41])[C:37]([CH3:40])([CH3:39])[CH3:38]>>[CH3:38][C:37]([CH3:40])([CH3:39])[CH2:36][NH:41][C:25]([C:23]1[N:22]=[CH:21][N:20]([C:18]2[CH:19]=[C:14]([C:12](=[O:13])[NH:11][C:9]3[CH:10]=[C:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:6]=[C:7]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])[C:8]=3[O:29][CH3:30])[CH:15]=[CH:16][C:17]=2[CH3:28])[CH:24]=1)=[O:26]
Reactant: COc1c(NC(=O)c2ccc(C)c(-n3cnc(C(=O)O)c3)c2)cc(C(C)(C)C)cc1NS(C)(=O)=O
Reactant: CC(C)(C)CN
Product: COc1c(NC(=O)c2ccc(C)c(-n3cnc(C(=O)NCC(C)(C)C)c3)c2)cc(C(C)(C)C)cc1NS(C)(=O)=O

Procedure:
The above carboxylic acid was then coupled with neopentylamine using the coupling procedure described in Example 4 to provide the title compound. 134-136° C.; ESI MS m/z 570 [C29H39N5O5S +H]+.
Reaction SMILES: Cl[CH2:2][Si:3]([O:10][CH2:11][CH3:12])([O:7][CH2:8][CH3:9])[O:4][CH2:5][CH3:6].[Si:13]([O:19][CH2:20][CH3:21])([O:16][CH2:17][CH3:18])(Cl)Cl>C1COCC1>[Si:3]([CH2:2][Si:13]([CH2:2][Si:3]([O:4][CH2:5][CH3:6])([O:10][CH2:11][CH3:12])[O:7][CH2:8][CH3:9])([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18])([O:10][CH2:11][CH3:12])([O:7][CH2:8][CH3:9])[O:4][CH2:5][CH3:6]
Reactant: CCO[Si](Cl)(Cl)OCC
Reactant: CCO[Si](CCl)(OCC)OCC
Solvent: C1CCOC1
Product: CCO[Si](C[Si](OCC)(OCC)OCC)(C[Si](OCC)(OCC)OCC)OCC
Temperature: 25 °C
Yield: 90 %

Procedure:
2 molar equivalents of ClCH2Si(OEt)3, 2 molar equivalents of Mg (sanded ribbon), and molar 1 equivalent of SiCl2(OEt)2 were added in flask with THF (Na treated) under N2. The mixture was stirred at room temperature until Mg disappeared. THF was removed by distillation. Pentane was added to extract the intermediate and then filtered to separate solid. After distillation of pentane, >90% yield crude (EtO)3Si—CH2—Si(OEt)2-CH2—Si(OEt)3 was obtained. (EtO)3Si—CH2—Si(OEt)2-CH2—Si(OEt)3 was directly reduced without further purification by 3 molar equivalents (based on the amount of (EtO)3Si—CH2—Si(OEt)2-CH2—Si(OEt)3) of LiAlH4 in ether in ice bath under N2. The mixture was stirred for ˜6 hours at room temperature. The volatiles were separated from solid by-products and LiAlH4 by vacuum transfer, and ether was removed from the collected volatives by distillation using a 55° C. bath. The final distillation give pure trisilapentane (TSP) as 70% overall yield. The pure TSP was analysed by GC as shown in FIG. 2, which indicates no undesired by-products remain. TSP: 1H NMR (C6D6): δ 3.95 (p, 2H, SiH2), 3.67 (t, 6H, SiH3), −0.40 (m, 4H, CH2). MS, m/z: 120 [M+].
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].FC1C=C(C=CC=1)C[O:12][C:13](=O)[C:14]1[C:15](=[CH:27][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=2)=[CH:29][CH:30]=1)[C:16](OCC1C=CC=C(F)C=1)=[O:17].O.S(=O)(=O)(O)O>C(OCC)C>[F:39][C:35]1[CH:34]=[C:33]([CH:38]=[CH:37][CH:36]=1)[CH2:32][O:31][C:28]1[CH:29]=[CH:30][C:14]([CH2:13][OH:12])=[C:15]([CH2:16][OH:17])[CH:27]=1
Reactant: O=C(OCc1cccc(F)c1)c1ccc(OCc2cccc(F)c2)cc1C(=O)OCc1cccc(F)c1
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: CCOCC
Product: OCc1ccc(OCc2cccc(F)c2)cc1CO
Yield: 75.1 %

Procedure:
To a suspension of lithium aluminum hydride (2.15 g, 56.9 mmol) and diethyl ether (150 mL) at 0° C. a solution of 4-(3-fluoro-benzyloxy)-phthalic acid bis-(3-fluoro-benzyl) ester (13.1 g, 25.9 mmol) in diethyl ether (150 mL) was added over 1 h. After a further 1.5 h water (100 mL) and sulfuric acid (2 M, 100 mL) was added and the resulting mixture was extracted with diethyl ether (2×100 mL). The combined extracts were then dried over sodium sulfate, filtered and evaporated to leave a clear oil which was purified by chromatography (SiO2, hexane:ethyl acetate 1:1 to 2:3) to afford the title product (5.1 g, 76%) as a white solid. MS m/e=260.6 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[C:5]([CH3:12])[C:6]=1[CH2:7][CH2:8][C:9](O)=[O:10].[C:13](N1C=CN=C1)([N:15]1C=CN=[CH:16]1)=O.CNC.C(N(CC)C(C)C)(C)C>ClCCl.O1CCCC1>[CH3:1][C:2]1[NH:3][CH:4]=[C:5]([CH3:12])[C:6]=1[CH2:7][CH2:8][C:9]([N:15]([CH3:16])[CH3:13])=[O:10]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1c[nH]c(C)c1CCC(=O)O
Agent: CNC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1c[nH]c(C)c1CCC(=O)N(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 83 %

Procedure:
To the suspension of 3-(2,4-dimethyl-1H-pyrrol-3-yl)-propionic acid (10 g, 60.8 mmol) in 60 mL of dichloromethane was added 1,1′-carbonyldiimidazole (11.6 g, 71.8 mmol) followed by the addition of 2 M dimethylamine solution in tetrahydrofuran (30 mL) and N,N-diisopropylethylamine (Hunig's base, 10 mL, 60.8 mmol). The dark red reaction mixture was stirred at room temperature overnight and poured into ice water. The organic layer was washed with brine until pH of 6, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified on a silica gel column eluting with dichloromethane-methanol (98:2) to give 9.8 g (83%) of 3-(2,4-dimethyl-1H-pyrrol-3-yl)-N,N-dimethyl-propionamide as a yellow oil.