Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[S:20][CH3:21].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH2:33][CH2:34]Br>C(#N)C>[CH3:21][S:20][C:11]1[CH:12]=[C:13]([C:16]([F:18])([F:19])[F:17])[CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[N:1]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:22]
Reactant: CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N
Reactant: BrCCOCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CSc1cc(C(F)(F)F)ccc1C(=O)N[C@@H]1CCCC[C@@H]1N1CCOCC1
Yield: 68.6 %

Procedure:
cis-N-(2-Amino-cyclohexyl)-2-methylsulfanyl-4-trifluoromethyl-benzamide (intermediate G) (264 mg, 0.79 mmol) was dissolved in 15 mL acetonitrile. Potassium carbonate (549 mg, 4 mmol) and bis(2-bromoethyl)ether (239 mg, 1 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0->140:10:1) yielded cis-2-methylsulfanyl-N-(2-morpholin-4-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow gum (218 mg, 68%), MS: m/e=403.3 [(M+H)+].
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](N)=[O:7])#[N:2].N([O-])=[O:13].[Na+].CS(O)(=O)=O>CS(C)=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:13])=[O:7])#[N:2]
Reactant: O=N[O-]
Reactant: N#Cc1cccc(C(N)=O)c1
Agent: CS(=O)(=O)O
Agent: [Na+]
Solvent: CS(C)=O
Product: N#Cc1cccc(C(=O)O)c1
Temperature: 25 °C
Yield: 87.4 %

Procedure:
m-Cyanobenzamide (2.92 g), sodium nitrite (2.76 g), and dimethyl sulfoxide (50 ml) were mixed and stirred vigorously at room temperature. To the mixture, methanesulfonic acid (3.95 g) was added dropwise over ten minutes, and further stirred vigorously for three hours. The solvent was removed under reduced pressure, and water (50 ml) was added to the residue. The precipitated crystals were collected through filtration, washed with water, and dried, to thereby obtain 2.57 g of m-cyanobenzoic acid (yield 88%). The obtained m-cyanobenzoic acid had a purity of 96%.
Reaction SMILES: [NH2:1][C@H:2]([C:4]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:8](=[O:16])[C:7]2=[C:17]([CH3:20])[CH:18]=[CH:19][N:6]2[N:5]=1)[CH3:3].[NH2:21][C:22]1[C:27]([C:28]([O:30][C:31]2[CH:36]=[CH:35][C:34]([S:37](=[O:41])(=[O:40])[NH:38][CH3:39])=[CH:33][CH:32]=2)=[O:29])=[C:26](Cl)[N:25]=[CH:24][N:23]=1.CCN(C(C)C)C(C)C.[F-].[Cs+]>C(O)(C)(C)C>[NH2:21][C:22]1[C:27]([C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([S:37](=[O:41])(=[O:40])[NH:38][CH3:39])=[CH:35][CH:36]=2)=[O:29])=[C:26]([NH:1][C@H:2]([C:4]2[N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:8](=[O:16])[C:7]3=[C:17]([CH3:20])[CH:18]=[CH:19][N:6]3[N:5]=2)[CH3:3])[N:25]=[CH:24][N:23]=1
Reactant: Cc1ccn2nc([C@H](C)N)n(-c3ccccc3)c(=O)c12
Reactant: CNS(=O)(=O)c1ccc(OC(=O)c2c(N)ncnc2Cl)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)(C)O
Product: CNS(=O)(=O)c1ccc(OC(=O)c2c(N)ncnc2N[C@@H](C)c2nn3ccc(C)c3c(=O)n2-c2ccccc2)cc1
Temperature: 80 °C
Yield: 14 %

Procedure:
(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (81 mg, 0.27 mmol), 4-(N-methylsulfamoyl)phenyl 4-amino-6-chloropyrimidine-5-carboxylate (135 mg, 0.39 mmol), DIEA (344 μl, 1.97 mmol) and cesium fluoride (150 mg, 0.99 mmol) were suspended in tert-butanol (10 ml) and the mixture was heated at 80° C. in a sealed tube for 24 h. The solvent was evaporated under reduced pressure and the reaction mixture was diluted with ethyl acetate and washed with saturated ammonium chloride solution and brine. After evaporation of the solvent, the residue was purified by reverse phase chromatography using SP1® Purification System to give 27 mg (14% yield) as a solid. Purity 99%.
Reaction SMILES: [CH2:1]([C:8]1[C:13]([C:14]([OH:16])=[S:15])=[CH:12][N:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17]I>C(#N)C.O>[CH2:1]([C:8]1[C:13]([C:14]([O:16][CH3:17])=[S:15])=[CH:12][N:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CI
Reactant: OC(=S)c1cnccc1Cc1ccccc1
Solvent: CC#N
Solvent: O
Product: COC(=S)c1cnccc1Cc1ccccc1
Reaction time: 7 h

Procedure:
A suspension of 2.45 g (0.01 mole) of 4-benzylthionicotinic acid in 35 mL of dry acetonitrile was treated with 1.52 g (0.01 mole) of 1,8-diazabicyclo[5,4,0]under-7-ene (DBU). 1.7 g (0.01 mole) of methyl iodide was added and stirring was continued for 7 hours. The reaction was carefully diluted with water to crystallize 430 mg of methyl 4-benzylthionicotinate which melted at 98°-99° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.[C:17]([NH2:21])(=[O:20])[CH:18]=[CH2:19].C(N(CC)CC)C>COCCOC>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH2:19][CH2:18][C:17](=[O:20])[NH2:21]
Reactant: Brc1ccc2[nH]cc(C[C@H]3CCCN3)c2c1
Reactant: C=CC(N)=O
Solvent: CCN(CC)CC
Solvent: COCCOC
Product: NC(=O)CCN1CCC[C@@H]1Cc1c[nH]c2ccc(Br)cc12

Procedure:
A stirred mixture of 5-bromo-3-(2(R)-pyrrolidinylmethyl)-1H-indole (Preparation 2; 600 mg, 2.1 mmol), acrylamide (168 mg, 2.4 mmol), triethylamine (0.60 ml) and 1,2-dimethoxyethane (11.9 ml), under nitrogen, was heated under reflux for 8 hours, allowed to cool, then partitioned between ethyl acetate (400 ml) and water (400 ml). The organic phase was separated, washed with water (400 ml), dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of 0.880 aqueous ammonia:methanol: dichloromethane (0.1:10:90 to 0.4:10:90), to afford the required product as a foam. Rf 0.26 (SS 7). [α]D25 +59° (c=0.1, CH3OH).
Reaction SMILES: [OH-].[Na+].[F:3][C:4]([F:14])([F:13])[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.[CH3:15][C:16]([CH3:18])=[O:17].Cl>CCCCCCC.C(O)(C)C>[F:3][C:4]([F:14])([F:13])[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[CH:15][C:16](=[O:17])[CH:18]=[CH:9][C:8]2[CH:7]=[CH:6][C:5]([C:4]([F:3])([F:13])[F:14])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Reactant: CC(C)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCCCC
Solvent: CC(C)O
Product: O=C(C=Cc1ccc(C(F)(F)F)cc1)C=Cc1ccc(C(F)(F)F)cc1
Temperature: 20 °C
Yield: 74.6 %

Procedure:
A solution of sodium hydroxide (15 g of 10% aqueous) is added with stirring, and under a nitrogen atmosphere to a solution of 4-trifluoromethylbenzaldehyde (6.42 g; 0.369 mol) in heptane (70 ml). Next, a solution of acetone (10.7 g; 0.184 mol) in heptane (30 ml) is added to the above two phase system at a temperature range of from 25° C. to 30° C. over a period of two hours. The reaction mixture is then stirred for two hours at 25° C. to 30° C. Concentrated hydrochloric acid (9.4 ml) and isopropyl alcohol (48 ml) are then added, the mixture heated at reflux for 1.5 hours, and is then cooled to 20° C. The precipitated solid is filtered, washed with heptane (40 ml), and water and dried under vacuum to afford 50.8 g of title product, 98.8% pure, mp 154° C. to 156° C. (yield: 73.7%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:13][CH:14]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]2)[CH:6]=[N:5][CH:4]=1.[ClH:27].CO>>[ClH:27].[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:6]=[N:5][CH:4]=1
Reactant: COc1cncc2cccc(NC3CCN(C(=O)OC(C)(C)C)CC3)c12
Agent: Cl
Solvent: CO
Product: COc1cncc2cccc(NC3CCNCC3)c12
Temperature: 25 °C

Procedure:
According to the method of Example 1, Step C, deprotection was performed (50° C., 2 hours) by using Intermediate 96 (358 mg) and 10% hydrogen chloride/methanol solution (10 ml). The reaction mixture was cooled to room temperature, and then the solvent was evaporated under reduced pressure. The residue was added with methanol (2 ml) and diethyl ether (6 ml). The deposited precipitates were collected by filtration and washed with diethyl ether to obtain the title compound (336 mg) as light yellow powdery solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([CH3:12])([CH3:11])[C:6]([O:8][CH2:9][CH3:10])=[O:7].NC(N)=[S:15].[OH-].[K+]>CCO>[SH:15][CH2:2][CH2:3][CH2:4][C:5]([CH3:12])([CH3:11])[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: NC(N)=S
Reactant: CCOC(=O)C(C)(C)CCCBr
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCOC(=O)C(C)(C)CCCS
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 89.9 %

Procedure:
Ethyl 5-bromo-2,2-dimethylpentanoate (9.1 g, 38.4 mmol) in 100 mL EtOH, was treated with thiourea (3.65 g, 48.0 mmol) and KOH (2.69 g, 48.0 mmol) and stirred at rt for 10 minutes. After gentle heating (40-45 C.) for one hour, the solution was cooled and quenched by adding it to a stirred solution of 100 g ice, 100 mL conc. HCl, and 100 mL water. This aqueous layer was then extracted with 3×200 mL methylene chloride. The combined organics were washed with 5% NaHCO3 (2×200 mL), then sat. NH4Cl (300 mL), and dried over Na2SO4 overnight. The organics were evaporated to yield the product as a clear, pale yellow oil (6.57 g, yield 90%). 1H NMR (300 MHz, CDCl3), d (ppm): 4.11 (q, 2H, J 7.1); 2.47 (t, 2H, J 6.9); 1.70-1.46 (m, 4H); 1.25 (t, 3H, J 7.1); 1.17 (s, 6H). 13C NMR (75 MHz, CDCl3), d (ppm): 177.5, 60.1, 41.9, 39.7, 32.3, 25.00, 24.95, 14.1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:8]([N:11]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:14][C:13]([CH2:22][N:23](C)[C:24](=O)OC(C)(C)C)=[CH:12]2)(=[O:10])=[O:9])[CH:5]=[N:6][CH:7]=1.[CH3:32][N:33](C)C=O.C(OCC)(=O)C.[ClH:43]>C(O)C.[C-]#N.[Zn+2].[C-]#N>[ClH:43].[CH3:24][NH:23][CH2:22][C:13]1[CH:14]=[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]([S:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([CH:3]=2)[C:32]#[N:33])(=[O:9])=[O:10])[CH:12]=1
Reactant: CN(Cc1cc(-c2ccccc2)n(S(=O)(=O)c2cncc(Br)c2)c1)C(=O)OC(C)(C)C
Reactant: CN(C)C=O
Agent: Cl
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CNCc1cc(-c2ccccc2)n(S(=O)(=O)c2cncc(C#N)c2)c1
Temperature: 100 °C
Reaction time: 1.5 h
Yield: 42 %

Procedure:
A mixture of tert-butyl ({1-[(5-bromopyridin-3-yl)sulfonyl]-5-phenyl-1H-pyrrol-3-yl}methyl)methylcarbamate (112 mg), zinc cyanide (50 mg) and N,N-dimethylformamide (4 mL) was degassed with argon gas. Tetrakis(triphenylphosphine)palladium (46 mg) was added, and the mixture was stirred at 100° C. for 1.5 hr. After cooling the reaction mixture to room temperature, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→3:2) to give a colorless oil. The obtained oil was dissolved in ethanol (2 mL), and a 4 mol/L hydrogen chloride-ethyl acetate solution (2 mL) was added. After stirring at room temperature for 1 hr, the mixture was concentrated under reduced pressure, and recrystallized from ethanol to give the title compound as a solid (yield 32.7 mg, 42%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([NH2:10])=[O:9])=[CH:6][N:5]=[CH:4][N:3]=1.CO[C:13](=O)[CH2:14][O:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:24][C:20]1[CH:19]=[C:18]([CH2:17][CH2:16][O:15][CH2:14][C:13]2[NH:10][C:8](=[O:9])[C:7]3[C:2]([N:1]=2)=[N:3][CH:4]=[N:5][CH:6]=3)[CH:23]=[CH:22][CH:21]=1
Reactant: NC(=O)c1cncnc1N
Reactant: COC(=O)COCCc1cccc(F)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=c1[nH]c(COCCc2cccc(F)c2)nc2ncncc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 0.9 %

Procedure:
A suspension of the commercially available 4-amino-5-pyrimidinecarboxamide [4786-51-0] (150 mg, 1.09 mmol) and of [2-(3-fluoro-phenyl)-ethoxy]-acetic acid methyl ester (254 mg, 1.19 mmol) in THF (7 ml) was treated with LiHMDS (1M solution in THF, 2.17 ml) and stirred overnight at ambient temperature. The resulting yellow suspension was filtered and the filtrate was evaporated to dryness and triturated with EtOAc/MeOH 9:1. The yellow solid was filtered off, the mother-liquid was evaporated and the remaining residue was purified by column chromatography (silica gel, EtOAc/MeOH, 9:1) to give the title compound as a white solid (3 mg, 1%), MS: m/e=301.1 [M+H+].
Reaction SMILES: [S:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:12]([F:13])=[CH:11][C:10]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[C:23]([CH3:25])[N:22]=[N:21]4)[O:16][C:15]3=[O:26])=[CH:9][C:8]=2[F:27])[CH2:3][CH2:2]1.I([O-])(=O)(=O)=[O:29].[Na+].C(#N)C>O>[F:13][C:12]1[CH:11]=[C:10]([N:14]2[CH2:18][C@H:17]([CH2:19][N:20]3[CH:24]=[C:23]([CH3:25])[N:22]=[N:21]3)[O:16][C:15]2=[O:26])[CH:9]=[C:8]([F:27])[C:7]=1[CH:4]1[CH2:5][CH2:6][S:1](=[O:29])[CH2:2][CH2:3]1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: Cc1cn(C[C@H]2CN(c3cc(F)c(C4CCSCC4)c(F)c3)C(=O)O2)nn1
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: Cc1cn(C[C@H]2CN(c3cc(F)c(C4CCS(=O)CC4)c(F)c3)C(=O)O2)nn1
Yield: 10.2 %

Procedure:
(5R)-3-[4-(Tetrahydro-2H-thiopyran-4-yl)-3,5-difluorophenyl]-5[(4-methyl-1,2,3-triazol-1-yl)methyl]oxazolidin-2-one (Example 24) (1.0 g, 2.5 mmol) was oxidized with sodium periodate (0.6 g, 2.8 mmol) as described for Intermediates 42 and 43. Reverse Phase chromatography with 10-25% acetonitrile in water containing 0.1% trifluoroacetic acid gave the Z-isomer as the first eluting product (105 mg), followed by elution of the E-isomer (60 mg) of the title compound.
Reaction SMILES: [C:1]([C:5]1[S:9][C:8]([NH2:10])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].CO[CH:13](OC)[N:14]([CH3:16])[CH3:15].CCCCCC>C1(C)C=CC=CC=1>[C:1]([C:5]1[S:9][C:8](/[N:10]=[CH:13]/[N:14]([CH3:16])[CH3:15])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nnc(N)s1
Reactant: COC(OC)N(C)C
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: CN(C)/C=N/c1nnc(C(C)(C)C)s1
Temperature: 100 °C

Procedure:
A mixture of 5-tert-butyl-1,3,4-thiadiazol-2-amine (Aldrich) (10.0 g, 63.6 mmol) and 1,1-dimethoxy-N,N-dimethylmethanamine (26.3 mL, 197 mmol) in 200 mL of toluene was heated at 100° C. for 12 hours. The mixture was cooled to room temperature and hexane was added. The solid was collected by filtration (hexane wash) to afford the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:12](=[O:20])[O:13][C:14]3([CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:10]=2[C:9]2[C@@H:8]([OH:21])[CH2:7][C:6]([CH3:23])([CH3:22])[CH2:5][C:4]=2[N:3]=1.N1C(C)=CC=CC=1C.[C:32]([Si:36](OS(C(F)(F)F)(=O)=O)([CH3:38])[CH3:37])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[Si:36]([O:21][C@H:8]1[CH2:7][C:6]([CH3:23])([CH3:22])[CH2:5][C:4]2[N:3]=[C:2]([Cl:1])[C:11]3[C:12](=[O:20])[O:13][C:14]4([CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)[C:10]=3[C:9]1=2)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:38])[CH3:37]
Reactant: CC1(C)Cc2nc(Cl)c3c(c2[C@@H](O)C1)C1(CCOCC1)OC3=O
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: CC1(C)Cc2nc(Cl)c3c(c2[C@@H](O[Si](C)(C)C(C)(C)C)C1)C1(CCOCC1)OC3=O
Temperature: 0 °C
Reaction time: 18 h

Procedure:
1.69 g (S)-4-chloro-9-hydroxy-7,7-dimethyl-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]-3-one are dissolved in 60 ml tetrahydrofurane and cooled to 0° C., 2.05 ml 2,6-lutidine and 3.71 ml trifluoromethanesulfonic acid-tert.-butyldimethylsilylester are added dropwise and the mixture is stirred for further 18 hours while warming to room temperature. Then the reaction is quenched by addition of 0.5 ml methanol. The mixture is partitioned between 0.1 M hydrochloric acid and ethylacetate. The aqueous phase is twice extracted with ethylacetate. The combined organic phases are dried with sodium sulphate and the solvents are evaporated in vacuo. The residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 70:30).
Reaction SMILES: [C:1]([C:3]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:11]=[C:12]([C:21]([NH:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]3[S:30][CH3:31])=[O:22])[C:13](=[O:20])[N:14]3[C:19]=2[CH:18]=[CH:17][CH:16]=[CH:15]3)[CH2:5][CH2:4]1)#[N:2].C1(C2[O:46]N2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>ClCCl>[C:1]([C:3]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:11]=[C:12]([C:21]([NH:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]3[S@:30]([CH3:31])=[O:46])=[O:22])[C:13](=[O:20])[N:14]3[C:19]=2[CH:18]=[CH:17][CH:16]=[CH:15]3)[CH2:5][CH2:4]1)#[N:2]
Reactant: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Reactant: CS[C@@H]1CCCC[C@H]1NC(=O)c1cc(CN2CCC(C#N)(c3ccccn3)CC2)c2ccccn2c1=O
Solvent: ClCCl
Product: C[S@](=O)[C@@H]1CCCC[C@H]1NC(=O)c1cc(CN2CCC(C#N)(c3ccccn3)CC2)c2ccccn2c1=O
Reaction time: 0.75 h

Procedure:
To a solution of rac-1-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-N-[(1R,2R)-2-(methylthio)cyclohexyl]-4-oxo-4H-quinolizine-3-carboxamide (Example 16, 0.035 g, 0.067 mmol) in 2 mL of dichloromethane at 0° C. was added 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (Davis reagent, 0.019 g, 0.074 mmol). After 45 min, the mixture was washed 3× with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave a proton NMR spectra consistent with theory and a high resolution mass spectrum (ES+) m/z of 532.2390 calculated for M+H+ [C29H34N5O3S: 532.2377]: 1H NMR (400 MHz, CDCl3) δ 10.02-9.99 (m, 1H), 9.42-9.40 (m, 1H), 8.66 (s, 1H), 8.60-8.57 (m, 1H), 8.22-8.19 (m, 1H); 7.76-7.67 (m, 2H), 7.62-7.60, 7.32-7.21 (m, 1H), 4.29-4.26 (m, 1H), 4.13-4.03 (m, 1H), 3.81 (s, 2H), 3.01-2.83 (m, 2H), 2.82-2.78 (m, 1H), 2.61 (s, 3H), 2.47-2.43 (m, 1H), 2.32-2.26 (m, 2H), 2.14-2.06 (m, 4H), 2.05-1.84 (m, 2H), 1.83-1.36 (m, 2H).
Reaction SMILES: [CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=1[N:19]1[N:23]=[CH:22][CH:21]=[N:20]1)=[O:10].Cl[C:25]1[N:30]=[CH:29][N:28]=[C:27]([N:31]([CH3:33])[CH3:32])[CH:26]=1>>[CH3:32][N:31]([CH3:33])[C:27]1[N:28]=[CH:29][N:30]=[C:25]([N:7]2[CH2:6][CH:5]3[CH2:1][N:2]([C:9]([C:11]4[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=4[N:19]4[N:20]=[CH:21][CH:22]=[N:23]4)=[O:10])[CH2:3][CH:4]3[CH2:8]2)[CH:26]=1
Reactant: COc1ccc(C(=O)N2CC3CNCC3C2)c(-n2nccn2)c1
Reactant: CN(C)c1cc(Cl)ncn1
Product: COc1ccc(C(=O)N2CC3CN(c4cc(N(C)C)ncn4)CC3C2)c(-n2nccn2)c1

Procedure:
The title compound was prepared utilizing (hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (Example 288, product from Step B) and 6-chloro-N,N-dimethylpyrimidin-4-amine. MS (ESI) mass calcd. C22H26N8O2, 434.49; m/z found 435.2 [M+H]+.