Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:12][N+:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH2:20][CH2:21][C:22](=[O:25])[NH:23][N:24]=3)=[CH:15][CH:14]=2)=[O:11])=[CH:6][CH:5]=1.[BH4-].[Na+].ClCCl>CO>[OH:11][CH:10]([C:7]1[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:9][CH:8]=1)[CH2:12][N:13]1[CH2:18][CH2:17][C:16]([C:19]2[CH2:20][CH2:21][C:22](=[O:25])[NH:23][N:24]=2)=[CH:15][CH2:14]1
Reactant: COc1ccc(C(=O)C[n+]2ccc(C3=NNC(=O)CC3)cc2)cc1
Agent: [BH4-]
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: COc1ccc(C(O)CN2CC=C(C3=NNC(=O)CC3)CC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 59.5 %

Procedure:
1-[(4-Methoxyphenyl)carbonylmethyl]-4-(4,5-dihydropyridazin-3 (2H)-one-6-yl)pyridinium bromide (300 mg, 0.74 mmol) was dissolved in methanol (5 ml), gradually added with sodium borohydride (280 mg, 7.4 mmol) under ice cooling and then stirred at room temperature overnight. The solvent was removed under reduced pressure. The residue obtained was added with dichloromethane, washed with water and dried over anhydrous magnesium sulfate. The solvent was removed to obtain the titled compound (145 mg) as colorless crystals.
Reaction SMILES: [OH:1]O.[Cl:3][C:4]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:5]=1[C:6]([NH:8][C:9]1[C:17]2[O:16][C:15]3[CH2:18][CH2:19][S:20][CH2:21][C:14]=3[C:13]=2[CH:12]=[CH:11][CH:10]=1)=[O:7].O>FC(F)(F)C(O)=O>[Cl:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:4]([Cl:3])[C:5]=1[C:6]([NH:8][C:9]1[C:17]2[O:16][C:15]3[CH2:18][CH2:19][S:20](=[O:1])[CH2:21][C:14]=3[C:13]=2[CH:12]=[CH:11][CH:10]=1)=[O:7]
Reactant: O=C(Nc1cccc2c3c(oc12)CCSC3)c1c(Cl)cccc1Cl
Reactant: OO
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1cccc2c3c(oc12)CCS(=O)C3)c1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of hydrogen peroxide in trifluoroacetic acid (1M, 0.32 ml) wa s added to a solution of 6-(2,6-dichlorobenzoylamino)-3,4-dihydro-1H-thiopyrano-[4,3-b]benzofuran (120 mg) in trifluoroacetic acid (2.5 ml) at 4° C. The mixture was stirred at ambient temperature for 30 minutes and to the mixture was added water. The separated solid was collected and dried. The obtained solid was suspended in hot ethanol and to the mixture was added water. The mixture was cooled and the separated solid was collected to give 6-(2,6-dichlorobenzoylamino)-3,4-dihydro-1H-thiopyrano[4, 3-b]-benzofuran 2-oxide (70 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:5]=[N:6][CH:7]=1.[Li]C(C)(C)C.C[O:27][B:28](OC)[O:29]C.Cl>C1COCC1>[CH:19]1[C:20]2[N:8]([C:4]3[CH:3]=[C:2]([B:28]([OH:29])[OH:27])[CH:7]=[N:6][CH:5]=3)[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:15]=2[CH:16]=[CH:17][CH:18]=1
Reactant: Brc1cncc(-n2c3ccccc3c3ccccc32)c1
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: OB(O)c1cncc(-n2c3ccccc3c3ccccc32)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 9-(5-bromopyridin-3-yl)-9H-carbazole (2B) (1.7 g, 5.3 mmol) in THF (20 mL) was added a solution of tert-BuLi (1.7M in hexanes, 6.8 mL, 11.6 mmol) at about −78° C. The crude mixture was then stirred at about −78° C. for about 40 min, then a freshly distilled trimethylborate (0.89 mL, 8 mmol) was added. The resulting solution was stirred at RT overnight, then a 5% HCl aqueous solution (50 mL) was added and the whole was stirred for about 20 hours. The mixture was extracted with ethyl acetate (250 mL) three times, the organic phase was collected; dried over Na2SO4, concentrated and recrystallized with hexanes/dichloromethane to give product 2C, a light yellow solid (0.9 g, 60% yield).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:40]=[CH:39][C:12]([C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:34][CH2:35][CH2:36][CH2:37][OH:38])[C:24](=[O:33])[C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[CH:18][CH:17]=2)=[O:14])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(=O)(O)[O-].[Na+].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl.CC(=O)OCC>[CH2:1]([O:8][C:9]1[CH:40]=[CH:39][C:12]([C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:34][CH2:35][CH2:36][CH:37]=[O:38])[C:24](=[O:33])[C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)=[CH:18][CH:17]=2)=[O:14])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCOc1ccc(C(=O)Oc2ccc(CN(CCCCO)C(=O)c3ccc(OC)cc3)cc2)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCCCCCCOc1ccc(C(=O)Oc2ccc(CN(CCCC=O)C(=O)c3ccc(OC)cc3)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Prepared from compound 87: To a stirring solution of 4-((N-(4-hydroxybutyl)-4-methoxybenzamido)methyl)phenyl 4-(heptyloxy)benzoate 87 (258 mg, 0.484 mmol) in DCM was added sodium bicarbonate (81 mg, 0.968 mmol) and Dess-Martin periodinane (308 mg, 0.726 mmol). The reaction mixture was stirred at room temperature for 2 h. The crude reaction was diluted with EA followed by NaHCO3 and aq. NaS2O3. The biphasic mixture was stirred overnight at room temperature. The organic phase was separated, washed with NaHCO3, dried over MgSO4, and concentrated to yield 264 mg of crude 4-((4-methoxy-N-(4-oxobutyl)benzamido)methyl)phenyl 4-(heptyloxy)benzoate INT-8. LCMS-ESI (m/z) calculated for C33H39NO6: 545; found 546 [M+H]+, tR=3.14 min (Method 3).
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:8]([CH3:9])[C:7]([C:10]2[C:18]3[C:13](=[C:14]([CH2:19][CH:20]=[C:21]([CH3:23])[CH3:22])[CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)=[C:6]([O:24]CC2C=CC(OC)=CC=2)[C:5](=[O:34])[CH:4]=1.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>ClCCl.O>[OH:24][C:6]1[C:5](=[O:34])[CH:4]=[C:3]([CH2:2][OH:1])[N:8]([CH3:9])[C:7]=1[C:10]1[C:18]2[C:13](=[C:14]([CH2:19][CH:20]=[C:21]([CH3:23])[CH3:22])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1
Reactant: COc1ccc(COc2c(-c3c[nH]c4c(CC=C(C)C)cccc34)n(C)c(CO)cc2=O)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: ClCCl
Solvent: O
Product: CC(C)=CCc1cccc2c(-c3c(O)c(=O)cc(CO)n3C)c[nH]c12
Reaction time: 2 h

Procedure:
To a stirring solution of 213 (75 mg, 0.16 mmol) in dichloromethane (1.5 mL) and water (88 μL) was added DDQ (38 mg, 0.17 mmol) at 0° C. After the cold bath was removed, the mixture was stirred for 2 h. The DDQH2 was removed by filtration and washed with EtOAc. The solution was washed with water and brine. The organic layer was dried over Na2SO4 and the solvent removed under vacuum. After flash column chromatography, the desired product was obtained as a yellow solid (45 mg, 81%). Mp: 215° C. (dec). 1H NMR (CDCl3): δ 1.65 (3H, s), 1.74 (3H, s), 2.49 (3H, s), 3.71 (2H, d, J=6.6 Hz), 4.67 (2H, s), 5.29 (1H, m), 5.67 (1H, s), 7.3-7.4 (2H, m), 7.81 (1H, m), 8.31 (1H, m). 13C NMR (CDCl3): δ 28.4, 30.9, 33.3, 34.7, 61.7, 109.7, 119.2, 123.5, 123.7, 125.0, 126.4, 127.6, 129.2, 129.9, 130.6, 133.8, 134.5, 137.7, 149.6, 160.5, 176.2. IR (KBr): 3360, 3197, 2971, 2856, 1604, 1552, 1298, 984 cm−1. HRMS (EI): m/z Calcd. C20H22N2O3 for [M+]338.1630. found 338.1632.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([CH2:17][C:18]3[NH:22][C:21]4[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=4[N:19]=3)[CH2:13][CH2:12]2)=[CH:5][CH:4]=1.CN(C)C(=O)C.[H-].[Na+].Cl[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[F:43]>O>[F:43][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][N:22]1[C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[N:19]=[C:18]1[CH2:17][CH:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:12][CH2:13]1
Reactant: COc1ccc(CCN2CCC(Cc3nc4ccccc4[nH]3)CC2)cc1
Reactant: Fc1ccccc1CCl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: COc1ccc(CCN2CCC(Cc3nc4ccccc4n3Cc3ccccc3F)CC2)cc1
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 65.5 %

Procedure:
To a stirred mixture of 3.5 parts of 2-[[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methyl]-1H-benzimidazole and 18 parts of N,N-dimethylacetamide were added portionwise 0.5 parts of a sodium hydride dispersion 59.4% at room temperature. After stirring for 35 minutes at room temperature and for 10 minutes at 60° C., a solution of 1.7 parts of 1-(chloromethyl)-2-fluorobenzene in 9 parts of N,N-dimethylacetamide was added dropwise at 60° C. After stirring for 10 minutes, the reaction mixture was cooled and poured into 150 parts of water. The product was extracted twice with 4-methyl-2-pentanone. The combined extracts were washed with water, dried, filtered and evaporated. The residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanone. The product was filtered off and dried, yielding 3.0 parts (65.5%) of 1-[(2-fluorophenyl)methyl]-2-[[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-methyl]-1H-benzimidazole; mp. 109.3° C. (515).
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].S(Cl)(Cl)=O.[Br:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[C:21]1[S:22][CH:23]=[CH:24][CH:25]=1.C(=O)(O)[O-].[Na+]>O>[Br:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[C:21]1[S:22][C:23]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:24][CH:25]=1
Reactant: Brc1ccc2ncnc(-c3cccs3)c2c1
Reactant: O=S(=O)(O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=S(Cl)Cl
Product: O=S(=O)(Cl)c1ccc(-c2ncnc3ccc(Br)cc23)s1
Temperature: 60 °C

Procedure:
14.4 mL chlorosulfonic acid and 14.42 mL thionyl chloride were added to 7.78 g of 6-bromo-4-(2-thienyl)quinazoline (compound in Production Example 96) under ice-cooling in a stream of nitrogen, and the mixture was heated at 60° C. for 16 hours, then poured into iced water, neutralized by adding a sodium bicarbonate solution and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate. The residue was recrystallized from ether/hexane, to give 2.47 g of the title compound (pale skin-colored crystals).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9](Cl)=[N:10][OH:11].[Cl:13][CH:14]([Cl:26])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]#[CH:25])=[O:16]>O1CCCC1.C(N(CC)CC)C>[Cl:13][CH:14]([Cl:26])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]1[O:11][N:10]=[C:9]([C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=2[Cl:8])[CH:25]=1)=[O:16]
Reactant: C#Cc1ccccc1NC(=O)C(Cl)Cl
Reactant: ON=C(Cl)c1c(Cl)cccc1Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(Nc1ccccc1-c1cc(-c2c(Cl)cccc2Cl)no1)C(Cl)Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2,6-Dichloro-N-hydroxybenzenecarboximidoyl chloride (1.25 g, 5.6 mmol) and 2,2-dichloro-N-(2-ethynylphenyl)acetamide (1.93 g, 8.5 mmol) were dissolved in anhydrous tetrahydrofuran (40 mL) and triethylamine (1.0 mL). The mixture was stirred at room temperature for 1 h then heated at reflux for 4 h to generate the 2,6-dichlorophenyl nitrile oxide intermediate, which reacted by a 1,3-dipolar cycloaddition reaction with 2,2-dichloro-N-(2-ethynylphenyl)acetamide. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with water and brine. The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting solid was purified by column chromatography on silica gel, eluting with 8:2 hexanes-ethyl acetate. The appropriate fractions were combined to give 2,2-dichloro-N-[2-[3-(2,6-dichlorophenyl)-5-isoxazolyl]phenyl]acetamide as a light brown solid, 1.24 g.
Reaction SMILES: Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[F-].[K+].[F:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=1B1OC(C)(C)C(C)(C)O1>O1CCCC1>[F:10][C:8]1[CH:9]=[C:2]([C:15]2[CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=[CH:19][C:14]=2[F:13])[C:3]([C:4]#[N:5])=[CH:6][CH:7]=1
Reactant: N#Cc1ccc(F)cc1Br
Reactant: CC1(C)OB(c2cc([N+](=O)[O-])ccc2F)OC1(C)C
Agent: [F-]
Agent: [K+]
Solvent: C1CCOC1
Product: N#Cc1ccc(F)cc1-c1cc([N+](=O)[O-])ccc1F
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A suspension of 2-bromo-4-fluorobenzonitrile (2.50 g, 12.5 mmol), potassium fluoride (2.40 g, 41.3 mmol) and 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (4.67 g, 17.5 mmol) in tetrahydrofuran (50 ml) was degassed with nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium(0) and tri-tert-butylphosphine (0.2 M solution in 1,4-dioxane, 3.7 ml) were added and the mixture stirred at ambient temperature for 15 min then at 50° C. for 18 h. After cooling to ambient temperature, the resulting dark suspension was poured onto 0.5 M sodium hydroxide solution (500 ml) and stirred vigorously for 2 h. The dark solid was collected by filtration, washed with water (100 ml) and isohexane (50 ml) and left to air dry which gave the title compound as a brown/black solid: 1H NMR (360 MHz, CDCl3) δ 7.25-7.33 (2H, m), 7.40-7.44 (1H, m), 7.86 (1H, dd, J 9, 6 Hz), 8.35-8.42 (2H, m).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([CH:15]([F:17])[F:16])[N:12]3[N:18]=[CH:19][C:20]([C:21]([OH:23])=O)=[C:11]3[N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:24][C:25]1[CH:34]=[CH:33][C:28]([C:29]([NH:31]O)=[NH:30])=[CH:27][N:26]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([CH:15]([F:16])[F:17])[N:12]3[N:18]=[CH:19][C:20]([C:21]4[O:23][N:31]=[C:29]([C:28]5[CH:33]=[CH:34][C:25]([NH2:24])=[N:26][CH:27]=5)[N:30]=4)=[C:11]3[N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: N=C(NO)c1ccc(N)nc1
Reactant: O=C(O)c1cnn2c(C(F)F)cc(-c3ccc(Cl)c(Cl)c3)nc12
Product: Nc1ccc(-c2noc(-c3cnn4c(C(F)F)cc(-c5ccc(Cl)c(Cl)c5)nc34)n2)cn1

Procedure:
The title compound was prepared from 5-(3,4-dichloro-phenyl)-7-difluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.7) (179 mg, 0.5 mmol) and 6-amino-N-hydroxy-nicotinamidine (example B.4) (114 mg, 0.75 mmol) according to general procedure II. Obtained after flash chromatography on silica gel (ethyl acetate/heptane) and further purification by crystallization (dichloromethane/hexane) as a yellow solid (92 mg, 39%). MS (ISP) 473.9 [(M+H)+]; mp 279° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:20][CH3:21])=[C:6]([C:8]([CH3:19])([CH3:18])[CH2:9][C:10](N2CCOCC2)=[O:11])[CH:7]=1.[CH:22]([Li])([CH3:24])[CH3:23]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:20][CH3:21])=[C:6]([C:8]([CH3:18])([CH3:19])[CH2:9][C:10](=[O:11])[CH:22]([CH3:24])[CH3:23])[CH:7]=1
Reactant: [Li]C(C)C
Reactant: COc1ccc(F)cc1C(C)(C)CC(=O)N1CCOCC1
Solvent: C1CCOC1
Product: COc1ccc(F)cc1C(C)(C)CC(=O)C(C)C
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a solution of 3-(5-fluoro-2-methoxyphenyl)-3-methyl-1-morpholin-4-ylbutan-1-one (0.45 g) in THF (2 mL) stirred under argon and cooled on dry ice/acetone was added isopropyl lithium (0.7M in pentane, 3 mL) over 10 minutes. The mixture was stirred for 20 minutes and quenched with EtOH (0.3 mL). The mixture was warmed to room temperature and water 1 mL was added. The organic phase was separated, washed, dried, filtered, and evaporated. The residue was fractionated over a short column of silica gel (eluent: hexanes-methylene chloride (1:1)) to give the product as an oil (0.40 g).
Reaction SMILES: [OH:1][N:2]1[C:6]([CH3:7])=[CH:5][S:4][C:3]1=[S:8].C(=O)([O-])O.[Na+].[C:14](Cl)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O>[C:14]([O:1][N:2]1[C:6]([CH3:7])=[CH:5][S:4][C:3]1=[S:8])(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1csc(=S)n1O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Cc1csc(=S)n1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
0.735 parts of 3-hydroxy-4-methylthiazol-2(3H)-thione were stirred in 50 parts of water and 0.84 parts of sodium hydrogen carbonate. The solution was screened and 0.9 parts of benzoyl chloride were added. The reaction mixture was stirred overnight at room temperature. A precipitate was formed which was separated by filtration, washed with cold water and recrystallised from ethanol to give 3-benzoyloxy-4-methylthiazol-2(3H)-thione, m.pt. 100°-102° C. By analysis the composition was found to be C, 52.4% wt; H, 3.6% wt; N, 5.6% wt and S, 25% wt. C11H9NO2S2 requires C, 52.6% wt; H, 3.6% wt; N, 5.6% wt and S, 25.5% wt.
Reaction SMILES: Cl.[CH3:2][NH:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]=[CH:16][N:17]=1)=[CH:9]2.C(N(CC)CC)C.[N:25]1([C:30](Cl)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:2][N:3]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]=[CH:16][N:17]=1)=[CH:9]2)[C:30]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:31]
Reactant: CNc1cccc2cc(-c3nccs3)[nH]c12
Reactant: O=C(Cl)N1CCCC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CN(C(=O)N1CCCC1)c1cccc2cc(-c3nccs3)[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 5 %

Procedure:
To a solution of N-methyl-2-(1,3-thiazol-2-yl)-1H-indole-7-amine hydrochloride (133 mg) and triethylamine (105 μL) in tetrahydrofuran (5 mL) was added pyrrolidine-1-carbonylchloride (100 mg). The reaction mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1) to give yellow crystals (8.2 mg, yield 5%). melting point 182° C.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:4][CH2:5][OH:6].[C:13]([O:17][C:18]([NH:20][C:21]1([C:36](O)=[O:37])[CH2:26][CH2:25][N:24]([C:27]2[C:28]3[CH:35]=[CH:34][NH:33][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:23][CH2:22]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CC(N(C)C)=O>[OH:6][CH2:5][CH2:4][C@H:3]([NH:2][C:36]([C:21]1([NH:20][C:18](=[O:19])[O:17][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:22][CH2:23][N:24]([C:27]2[C:28]3[CH:35]=[CH:34][NH:33][C:29]=3[N:30]=[CH:31][N:32]=2)[CH2:25][CH2:26]1)=[O:37])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CCN(c2ncnc3[nH]ccc23)CC1
Reactant: N[C@@H](CCO)c1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)NC1(C(=O)N[C@@H](CCO)c2ccccc2)CCN(c2ncnc3[nH]ccc23)CC1
Temperature: 20 °C
Reaction time: 24 h
Yield: 48.9 %

Procedure:
(S)-3-Amino-3-phenylpropan-1-ol hydrochloride (260 mg, 1.38 mmol) was added in one portion to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 21) (500 mg, 1.38 mmol) and DIPEA (0.967 mL, 5.53 mmol) in DMA (5 mL). O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (579 mg, 1.52 mmol) was added and the resulting solution was stirred at 20° C. for 24 hours. The reaction mixture was evaporated to dryness then diluted with EtOAc (300 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 2 to 6% MeOH with ammonia in DCM. Fractions were evaporated to afford (S)-tert-butyl 4-(3-hydroxy-1-phenylpropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (334 mg, 48.8%) as a white solid. The product (334 mg, 0.67 mmol) was suspended in dioxane (5.00 mL) and 4M hydrogen chloride in dioxane (0.961 mL, 27.67 mmol) added. The reaction was stirred at ambient temperature for 2 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 3.5N ammonia/MeOH and pure fractions were evaporated to dryness. The resulting gum was triturated with EtOAc to give a solid which was collected by filtration and dried under vacuum to give (S)-4-amino-N-(3-hydroxy-1-phenylpropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (93 mg, 17.0%) as an off white solid.
Reaction SMILES: [CH2:1]([OH:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10].[C:12](O)(=[O:22])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21]>C(OCC)(=O)C.CCCCCC>[C:1]([O:22][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10]
Reactant: C=CCCCCCCCC(=O)O
Reactant: C=CCCCCCCCCO
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: C=CCCCCCCCCOC(=O)CCCCCCCC=C
Yield: 92.7 %

Procedure:
Compound G was prepared from 9-decen-1-ol and 9-decenoic acid following the general procedure already discussed and shown in FIG. 12. Pure compound G was a colorless oil by column chromatography with Ethyl acetate/Hexane=1:50.
Reaction SMILES: [C:1]([OH:9])(=[O:8])[CH:2]([CH2:4][CH:5]([CH3:7])[CH3:6])[OH:3].[OH-].[Na+].[CH2:12]([C@H:14]1[CH2:19][C@H:18]2[C@H:20]3[C@H:29]([CH2:30][CH2:31][C@:16]2([CH3:17])[C@H:15]1[O:33][C:34](=[O:37])[CH2:35]Br)[C@@H:28]1[C:23](=[CH:24][C:25](=[O:32])[CH2:26][CH2:27]1)[CH2:22][CH2:21]3)[CH3:13].CN(C=O)C>CC(C)=O>[CH2:12]([C@H:14]1[CH2:19][C@H:18]2[C@H:20]3[C@H:29]([CH2:30][CH2:31][C@:16]2([CH3:17])[C@H:15]1[O:33][C:34](=[O:37])[CH2:35][O:8][C:1](=[O:9])[CH:2]([OH:3])[CH2:4][CH:5]([CH3:7])[CH3:6])[C@@H:28]1[C:23](=[CH:24][C:25](=[O:32])[CH2:26][CH2:27]1)[CH2:22][CH2:21]3)[CH3:13]
Reactant: CC[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]2(C)[C@H]1OC(=O)CBr
Reactant: CC(C)CC(O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: CC[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]2(C)[C@H]1OC(=O)COC(=O)C(O)CC(C)C
Yield: 96.3 %

Procedure:
In 2.0 ml of acetone is dissolved 0.26 g of leucic acid, and 1.0 ml of 2N-NaOH is added, followed by addition of 0.44 g of 16β-ethyl-17β-bromoacetoxy-4-estren-3-one and 15 ml of DMF. The mixture is refluxed for 3 hours, and thereafter treated in the same manner as Example 26. The reaction mixture is then subjected to column chromatography. Following passage of 50 ml of diisopropyl ether-n-hexane (1:1), elution is carried out with 200 ml of diisopropyl ether. The eluate is evaporated under reduced pressure to remove the solvent, giving 0.475 g of the above-identified compound as a viscous oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:30])[C@H:7]([NH:22]C(OC(C)(C)C)=O)[CH2:8][CH2:9][CH2:10][N:11]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]1=[O:21])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([O:5][C:6](=[O:30])[C@H:7]([NH2:22])[CH2:8][CH2:9][CH2:10][N:11]1[C:12](=[O:21])[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19]1=[O:20])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@H](CCCN1C(=O)c2ccccc2C1=O)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)OC(=O)[C@H](N)CCCN1C(=O)c2ccccc2C1=O
Reaction time: 1 h
Yield: 70.2 %

Procedure:
A solution of the title G compound, (2R)-(t-butyloxycarbonylamino)-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester (4.83 g, 11.55 mmol) in 18 mL of dichloromethane is treated with trifluoroacetic acid (TFA; 6.00 mL, 78 mmol) at 0° C. After stirring for 1 h at this temperature, the solution is concentrated under reduced pressure without heating, and the residue is partitioned between 100 mL of ethyl acetate and 50 mL of 1M aqueous NaHCO3. The organic phase is dried over anhydrous Na2SO4 and concentrated. Chomatography on silica gel (eluant; 1/1—ethyl acetate/hexane) affords 2.58 g (70%) of (2R)-amino-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester as a colorless foam: NMR(CDCl3) 1.46 (s, 9H), 1.80-2.06 (m, 4H), 3.73 (t, 2H, J=6.2), 3.97 (t, 1H, J=6.3), 7.68-7.71 (m, 2H), 7.82-7.85 (m, 2H).