Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN.[O:3]=[C:4]1[N:10]2[CH2:11][CH2:12][CH2:13][C@H:9]2[C:8]2=[C:14]([C:17]3[O:21][C:20]([CH2:22][N:23]4C(=O)C5C(=CC=CC=5)C4=O)=[N:19][N:18]=3)[N:15]=[CH:16][N:7]2[C:6]2[CH:34]=[CH:35][S:36][C:5]1=2>C(O)C>[NH2:23][CH2:22][C:20]1[O:21][C:17]([C:14]2[N:15]=[CH:16][N:7]3[C:6]4[CH:34]=[CH:35][S:36][C:5]=4[C:4](=[O:3])[N:10]4[CH2:11][CH2:12][CH2:13][C@H:9]4[C:8]=23)=[N:18][N:19]=1
Reactant: O=C1c2ccccc2C(=O)N1Cc1nnc(-c2ncn3c2[C@@H]2CCCN2C(=O)c2sccc2-3)o1
Agent: CN
Solvent: CCO
Product: NCc1nnc(-c2ncn3c2[C@@H]2CCCN2C(=O)c2sccc2-3)o1
Reaction time: 1 h
Yield: 67.8 %

Procedure:
30 ml of methylamine (33% in ethanol) were added dropwise at 70° to a suspension of 2.5 g (5.3 mmol) of (S)-2-[5-(8-oxo-10,11,12,12a-tetrahydro-8H-imidazo[5,1-c]pyrrolo[1,2-a]thieno[3,2-e][1,4]diazepin-1-yl)-1,3,4-oxadiazol-2-ylmethyl]-2,3-dihydro-1H-isoindole-1,3-dione in 30 ml of ethanol and the mixture was stirred at 70° for one hour. The precipitate obtained was filtered off while hot and the yellowish powder obtained was washed colourless with ethanol. There were obtained 1.23 g (68%) of (S)-1-(5-aminomethyl-1,3,4-oxadiazol-2-yl)-10,11,12,12a-tetrahydro-8H-imidazo[5,1-c]pyrrolo[1,2-a]thieno[3,2-e]-[1,4]diazepin-8-one as a colourless powder of m.p. 214°-216°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:22][CH2:21][N:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:19]4)[C:14]([F:27])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH2:28](S(Cl)(=O)=O)[CH2:29]C>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:22][CH2:21][N:20]([S:23]([CH2:26][CH2:28][CH3:29])(=[O:24])=[O:25])[CH2:19]4)[C:14]([F:27])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CCCS(=O)(=O)Cl
Reactant: CS(=O)(=O)N1CC[C@H](Nc2nc(-c3c[nH]c4ncc(Cl)cc34)ncc2F)C1
Product: CCCS(=O)(=O)N1CC[C@H](Nc2nc(-c3c[nH]c4ncc(Cl)cc34)ncc2F)C1
Yield: 36 %

Procedure:
According to the procedure for compound 398 using propylsulfonyl chloride (20 mg, 0.14 mmol) afforded 15.5 mg (36% yield) of 410, as a solid.
Reaction SMILES: [N:1]([CH2:4][C@H:5]1[O:13][C@H:12]2[C@H:8]([N:9]=[C:10]([NH:14][CH2:15][CH3:16])[S:11]2)[C@@H:7]([OH:17])[C@@H:6]1[OH:18])=[N+:2]=[N-:3].C(O)C.[C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)#[CH:23]>[Cu].O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O.CC(O)(C)C>[CH2:15]([NH:14][C:10]1[S:11][C@H:12]2[O:13][C@H:5]([CH2:4][N:1]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[N:3]=[N:2]3)[C@@H:6]([OH:18])[C@H:7]([OH:17])[C@H:8]2[N:9]=1)[CH3:16]
Reactant: CCNC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CN=[N+]=[N-])O[C@@H]2S1
Reactant: C#Cc1ccccn1
Agent: [Cu+2]
Agent: [Cu]
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CCO
Solvent: CC(C)(C)O
Product: CCNC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](Cn3cc(-c4ccccn4)nn3)O[C@@H]2S1
Yield: 25.5 %

Procedure:
In a 5 mL seal vial equipped with a stir bar, a septum was added (3aR,5R,6S,7R,7aR)-5-(azidomethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-6,7-diol (40.00 mg; 0.15 mmol; 1.00 eq.), copper Not supported by ACD (65.10 mg; 1.02 mmol; 7.00 eq.) and copper (2+) sulfate pentahydrate (7.31 mg; 0.03 mmol; 0.20 eq.). The vial was evacuated and filled with N2. This procedure was repeated for twice before ethanol (0.40 ml)/water (0.60 ml)/2-methylpropan-2-ol (1.00 ml) and 2-ethynylpyridine (0.03 ml; 0.29 mmol; 2.00 eq.) was added into the mixture. The mixture was stirred at room temperature for overnight before 3 mL H2O was added into the mixture and dried via lyophilization. The mixture was purified with Yamazen C1 acidic condition affording 14.4 mg (20.1%) of the title compound as a white solid (HPLC 99%, retention time=1.73 min) once lyophilized.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[S:11](Cl)(=[O:13])=[O:12].[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[S:11]([NH:8][C:4]1[CH:3]=[CH:2][CH:1]=[C:19]2[C:20]=1[N:15]=[CH:16][CH:17]=[CH:18]2)(=[O:13])=[O:12]
Reactant: Cc1cccc([N+](=O)[O-])c1S(=O)(=O)Cl
Reactant: c1ccncc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: Cc1cccc([N+](=O)[O-])c1S(=O)(=O)Nc1cccc2cccnc12
Yield: 39 %

Procedure:
In a similar fashion using route 14 general procedure 27, 8-aminoqunoline (1.6 g, 11.1 mmol), 2-methyl-6-nitro-benzenesulfonyl chloride (Intermediate 451) (3.5 g, 14.4 mmol), pyridine (10 ml), DMAP (cat.) and DCM (5 ml) gave the title compound (1.5 g, 39%) after purification by column chromatography with n-hexane/EtOAc (85:15) as the eluent.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7](Cl)[N:6]=[C:5](Cl)[N:4]=1.[C:11]([CH2:13][C:14]([O:16][CH3:17])=[O:15])#[N:12].[H-].[Na+]>>[C:14]([CH:13]([C:11]#[N:12])[C:5]1[N:6]=[C:7]([CH:13]([C:14]([O:16][CH3:17])=[O:15])[C:11]#[N:12])[N:8]=[C:3]([O:2][CH3:1])[N:4]=1)([O:16][CH3:17])=[O:15]
Reactant: COc1nc(Cl)nc(Cl)n1
Reactant: COC(=O)CC#N
Agent: [H-]
Agent: [Na+]
Product: COC(=O)C(C#N)c1nc(OC)nc(C(C#N)C(=O)OC)n1
Yield: 82 %

Procedure:
The preparation was carried out in the same way as indicated in Example II. 2.70 g (0.015 moles) of 2-methoxy-4,6-dichloro-s-triazine were converted with the reaction product of 5.95 g (0.06 moles) of methyl cyanoacetate and 1.44 g (0.06 moles) of sodium hydride. After extraction with methanol and petroleum ether (boiling point 40°-60° C.) 3.74 g of 2,4-di-(carbomethoxycyanomethyl)-6-methoxy-s-triazine were obtained in 82% yield. The UV absorption maxima were at' ##EQU18##
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7](O)[CH3:8])[CH:2]=1.[CH3:10][C:11]1[C:17]([CH3:18])=[C:16]([OH:19])[C:15]([CH3:20])=[CH:14][C:12]=1[OH:13].FC(F)(F)S(O)(=O)=O>ClC(Cl)C>[CH3:20][C:15]1[C:16](=[O:19])[C:17]([CH3:18])=[C:11]([CH3:10])[C:12](=[O:13])[C:14]=1[CH:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[CH3:8]
Reactant: Cc1cc(O)c(C)c(C)c1O
Reactant: CC(O)c1cccnc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: CC(Cl)Cl
Product: CC1=C(C)C(=O)C(C(C)c2cccnc2)=C(C)C1=O
Temperature: 0 °C
Yield: 61.5 %

Procedure:
To a solution of 4.0 g (32.5 mmol) of 1-(3-pyridyl)ethanol in 25 ml of dichloroethane, 4.96 g (32.6 mmol) of 2,3,5-trimethylhydroquinone and 4.5 ml (50.9 mmol) of trifluoromethanesulfonic acid were added and refluxed by heating for 20 hours in argon atomosphere. After cooling, ice water was added, washed with ethyl acetate to eliminate neutral substances, and made weakly alkaline with a saturated solution of sodium hydrogen carbonate. The resultant substance was extracted with ethyl acetate, and the extract was washed with water, dried, oxidized with air and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (isopropyl ether-ethyl acetate (1:2)), to give 5.1 g of 3,5,6-trimethyl-2-[1-(3-pyridyl)ethyl]-1,4benzoquinone (yield 61%). Physical data of this compound are shown in Table 1.
Reaction SMILES: [CH2:1]([O:3][C:4]([NH:6][C@H:7]([C:15](N(C)OC)=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC>[CH2:1]([O:3][C:4]([NH:6][C@H:7]([CH:15]=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N[C@@H](Cc1ccccc1)C(=O)N(C)OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CCOC(=O)N[C@H](C=O)Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.67 h

Procedure:
To 56 mg (200 μmole) (12), prepared in Step 1, above, was added 2 mL of dry Et2O, and the solution was cooled to 0° C. Lithium aluminum hydride (9.5 mg, 50 μmole, 1.25 eq. H-) was added, and the reaction was monitored by TLC. After 2 h the reaction was quenched with ca. 4 mL ethyl acetate and the solution stirred for 40 min. The organic layer was washed 2× with dilute HCl, 2× with saturated NaHCO3, and 1× with brine. The organic layer was dried with Na2SO4, filtered, and the filtrate evaporated. The residue was pumped on high vacuum overnight, then purified by flash silica gel chromatography to give the title compound. NMR (300 MHz, CDCl3): δ 9.60 (s, CHO, 1H), 7.20 (m, Ph, 5H), 4.45 (br dd, Phe-α, 1H), 4.08 (q, CH3CH2OCO, 2H), 3.08 (d, Phe-β, 2H), 1.20 (t, CH3CH2OCO, 3H).
Reaction SMILES: [C:1]([C:3]1[CH:14]=[CH:13][C:6]([CH2:7][CH:8]([C:11]#[N:12])[C:9]#[N:10])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].Cl[CH:18]=[CH:19][CH:20]([Cl:22])[Cl:21]>CN(C)C=O>[C:1]([C:3]1[CH:14]=[CH:13][C:6]([CH2:7][C:8]([CH:18]=[CH:19][CH:20]([Cl:22])[Cl:21])([C:11]#[N:12])[C:9]#[N:10])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(CC(C#N)C#N)cc1
Reactant: ClC=CC(Cl)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1ccc(CC(C#N)(C#N)C=CC(Cl)Cl)cc1
Yield: 34.1 %

Procedure:
Using 0.37 g of (4-cyanobenzyl)malononitrile, 5 ml of N,N-dimethylformamide, 0.12 g of sodium hydride (60% in oil), and 0.25 g of 1,3,3-trichloropropene, and according to the process described in the Production Example 1, there was obtained 0.17 g of 2-(4-cyanobenzyl)-2-(3,3-dichloropropenyl)malononitrile (the present compound (56)).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:16](=O)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])[C:9]2=O)=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])[CH2:9]2)=[CH:27][CH:28]=1
Reactant: COCCOCCOc1cccc2c1C(=O)N(Cc1ccc(OC)cc1)C2=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COCCOCCOc1cccc2c1CN(Cc1ccc(OC)cc1)C2
Temperature: 60 °C
Reaction time: 18 h
Yield: 98.7 %

Procedure:
2-(4-Methoxy-benzyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-isoindole-1,3-dione (149 mg, 0.38 mmol) was treated with a 1M solution of lithium aluminium hydride in THF (5 mL, 5 mmol). The mixture was maintained at r.t. for 4 hours, 60° C. for 1 hour, then r.t. for a further 18 hours. The mixture was then cooled in ice and quenched by the dropwise addition of water (0.2 mL), 2N sodium hydroxide solution (0.4 mL) and water (0.4 mL). Magnesium sulfate was added, followed by ethyl acetate and then the mixture was stirred at r.t. for 15 minutes. The solids were removed by filtration, being well washed with ethyl acetate. Concentration of the filtrate gave a residue which was absorbed onto an SCX cartridge and washed with 5% methanol/dichloromethane then eluted with 10% 1M ammonia in methanol/dichloromethane to afford the title compound (134 mg, 97%). 1H NMR (methanol-d4) 7.43-7.39 (2H, m), 7.27 (1H, t), 6.99-6.96 (2H, m), 6.90 (1H, d), 6.88 (1H, d), 4.33 (2H, s), 4.28 (2H, s), 4.23 (2H, s), 4.18-4.15 (2H, m), 3.85-3.79 (5H, m), 3.67-3.64 (2H, m), 3.54-3.51 (2H, m), 3.33 (3H, s). MS: [M+H]+ 358.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19](Br)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1.[NH+:30]1([CH2:36][B-](F)(F)F)[CH2:35][CH2:34][S:33][CH2:32][CH2:31]1>>[CH3:1][O:2][C:3](=[O:29])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([CH2:36][N:30]5[CH2:35][CH2:34][S:33][CH2:32][CH2:31]5)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3ccc(C(F)(F)F)c4Br)ccc21
Reactant: F[B-](F)(F)C[NH+]1CCSCC1
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3ccc(C(F)(F)F)c4CN3CCSCC3)ccc21

Procedure:
The title compound is prepared from {(S)-6-[(R)-4-bromo-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester and (thiomorpholinium-4-ylmethyl)trifluoroborate following a procedure analogous to that described for Intermediate 3. LC (method 1): tR=1.19 min; Mass spectrum (ESI+): m/z=508 [M+H]+.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[CH3:19][C:20]1[CH:21]=[N:22][C:23]2[CH2:24][CH2:25][CH2:26][CH2:27][C:28]=2[CH:29]=1.C[Si]([N:34]=[C:35]=[S:36])(C)C.Cl>C1C=CC=CC=1.O>[CH3:19][C:20]1[CH:21]=[N:22][C:23]2[CH:24]([C:35](=[S:36])[NH2:34])[CH2:25][CH2:26][CH2:27][C:28]=2[CH:29]=1
Reactant: C[Si](C)(C)N=C=S
Reactant: Cc1cnc2c(c1)CCCC2
Agent: Cl
Agent: [Li]CCCC
Solvent: c1ccccc1
Solvent: CCCCCC
Solvent: O
Product: Cc1cnc2c(c1)CCCC2C(N)=S
Yield: 43.1 %

Procedure:
A solution of di-isopropylamine (11.11 g., 0.11 mol) in benzene (50 ml.) was cooled to 0° C and treated portionwise with a 9% w/v solution of butyl lithium in hexane (79 ml., 0.11 mol.). After 45 minutes at 0° C the solution was treated dropwise with 3-methyl-5,6,7,8-tetrahydroquinoline (14.7 g., 0.10 mol.) with rapid stirring and under an atmosphere of nitrogen. After 11/2 hours at 0° C the red suspension was treated portionwise over 2 minutes with trimethylsilylisothiocyanate (14.7 ml., 0.11 mol.) and the reaction mixture stirred at 0° C for 1/2 hour and at room temperature for 1 hour. The reaction mixture was diluted with water (25 ml.) and the pH adjusted to 2.0 with 2N HCl. The mixture was extracted with ethylacetate (3 × 25 ml.) and the combined extracts discarded. The aqueous solution was adjusted to pH 10.0 with sodium carbonate and extracted with chloroform (3 × 50 ml.). The combined extracts were washed with saturated brine (1 × 50 ml.), dried (MgSO 4) and the solvent removed in vacuo. The residual oily solid was triturated with n-hexane (100 ml.) and the solid filtered and recrystallised from isopropanol to give the title compound as pale yellow needles (8.9 g., 43%) m.p. 153° C identical in all respects to authentic material. The filtrate was analysed by g.l.c. (10% SE30, T = 160° C and identified as a mixture of 8-cyano-3-methyl-5,6,7,8-tetrahydroquinoline (1 g., 6% yield based on starting material) and recovered 3-methyl-5,6,7,8-tetrahydroquinoline (7.17 g., 48% yield based on starting material).
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([C:12](=[N:14][OH:15])[NH2:13])=[CH:10][CH:11]=1)=[O:4].[C:16]1(=O)[O:21][C:19](=[O:20])[CH2:18][CH2:17]1>CN(C)C=O.O>[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:16]([CH2:17][CH2:18][C:19]([OH:21])=[O:20])[O:15][N:14]=2)=[N:8][CH:7]=1)=[O:4]
Reactant: O=C1CCC(=O)O1
Reactant: NC(=NO)c1ccc(NC(=O)CCl)cn1
Solvent: CN(C)C=O
Solvent: O
Product: O=C(O)CCc1nc(-c2ccc(NC(=O)CCl)cn2)no1

Procedure:
A mixture of compound of example 4 (0.228 g, 1 mmol) and succinic anhydride was stirred in dimethyl formamide (5 mL), at a temperature in the range of 115-120° C. for a period of 16 hours. The reaction mixture was cooled, diluted with water, and extracted with ethyl acetate (3×50 mL). The organic layer was washed with brine, dried over sodium sulfate and concentrated. The crude product obtained was purified over silica gel using ethyl acetate as eluent. The pure fractions were concentrated and crystallized using ethyl acetate/petroleum ether, to obtain the title compound.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1([CH:10]([CH2:13][OH:14])[CH2:11][OH:12])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.CO[C:17](OC)([CH3:19])[CH3:18].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CC(C)=O>[CH3:18][C:17]1([CH3:19])[O:12][CH2:11][CH:10]([C:4]2([CH2:3][CH2:2][OH:1])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]2)[CH2:13][O:14]1
Reactant: COC(C)(C)OC
Reactant: OCCC1(C(CO)CO)CCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Product: CC1(C)OCC(C2(CCO)CCCCC2)CO1
Temperature: 25 °C
Reaction time: 48 h
Yield: 79.3 %

Procedure:
To a solution of 2-[1-(2-hydroxyethyl)cyclohexyl]propane-1,3-diol (200 mg) in acetone (10 mL) were added 2,2,-dimethoxypropane (206 mg) and p-toluenesulfonic acid (17 mg) at room temperature. After stirring the solution at room temperature for 48 hours, a saturated aqueous sodium bicarbonate solution was added thereto, and it was concentrated under reduced pressure. To the resulting residue were added diethyl ether and water, and it was extracted with diethyl ether. The organic layer was washed in turn with 0.5N hydrochloric acid, water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by chromatography (silica gel, hexane:ethyl acetate=1:1 to 1:2) to give the title compound (190 mg).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([C:9]2[CH2:13][CH:12]([C:14]([OH:16])=O)[O:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1.[NH:19]1[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[F:17][C:2]([F:1])([F:18])[C:3]1[CH:4]=[C:5]([C:9]2[CH2:13][CH:12]([C:14]([N:19]3[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:20]3)=[O:16])[O:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCNC1
Reactant: O=C(O)C1CC(c2cccc(C(F)(F)F)c2)=NO1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CCN(C(=O)C2CC(c3cccc(C(F)(F)F)c3)=NO2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.9 %

Procedure:
To a solution of 3-[3-(trifluoromethyl)phenyl]-4,5-dihydroisoxazole-5-carboxylic acid (259 mg, 1 mmol) and tert-butyl (3S)-pyrrolidin-3-ylcarbamate (186 mg, 1 mmol) in DMF (0.5 mL) and methylene chloride (5 mL) at 0° C. was added triethylamine (120 mg, 1.2 mmol) and benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (442 mg, 1 mmol). The mixture was allowed to warm to room temperature over 1 h and stirred at room temperature for 1 h. The mixture was concentrated in vacuo, and the residue was chromatographed on silica gel, eluting with 1% NH4OH in ethyl acetate to give the desired coupling intermediate (410 mg) as a white solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:7][CH:8]2[CH2:10][CH2:9]2)[S:5][CH:6]=1.[O:11]=[S:12]1(=[O:39])[CH2:17][CH2:16][CH:15]([C:18]2[C:26]3[C:21](=[C:22](C(N)=O)[CH:23]=[C:24](B4OC(C)(C)C(C)(C)O4)[CH:25]=3)[NH:20][CH:19]=2)[CH2:14][CH2:13]1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>O1CCOCC1.O>[CH:8]1([CH2:7][C:4]2[S:5][CH:6]=[C:2]([C:24]3[CH:25]=[C:26]4[C:21](=[CH:22][CH:23]=3)[NH:20][CH:19]=[C:18]4[CH:15]3[CH2:16][CH2:17][S:12](=[O:11])(=[O:39])[CH2:13][CH2:14]3)[CH:3]=2)[CH2:10][CH2:9]1
Reactant: CC1(C)OB(c2cc(C(N)=O)c3[nH]cc(C4CCS(=O)(=O)CC4)c3c2)OC1(C)C
Reactant: Brc1csc(CC2CC2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Solvent: ClCCl
Product: O=S1(=O)CCC(c2c[nH]c3ccc(-c4csc(CC5CC5)c4)cc23)CC1
Temperature: 100 °C
Yield: 24.6 %

Procedure:
4-Bromo-2-(cyclopropylmethyl)thiophene (50 mg, 0.23 mmol), 3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (80 mg, 0.19 mmol) and K2CO3 (105 mg, 0.76 mmol) was taken up in 1,4-dioxane (3 mL) and water (1.5 mL) in a microwave vial. The mixture was degassed by bubbling argon through it for 5 min. PdCl2(dppf).DCM adduct (25 mg, 0.031 mmol) was added, and the reaction was heated in a microwave for 5 min at 100° C. The reaction mixture was concentrated, diluted in DMSO, and purified on a Gilson HPLC(NH4OH buffer). The desired fractions were concentrated, giving 18 mg (22%) of the title compound.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:10]2[C:6]([S:7][C:8]([C:11]3[C@H:12]([CH3:35])[C@@H:13]4[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]4[C:15]=3[C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=3)=[O:17])=[CH:9]2)=[C:5]([S:36][CH3:37])[N:4]=1.ClC1C=CC=C(C(OO)=[O:46])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[OH:33][C@@H:31]([C@H:30]1[C:29](=[O:34])[N:14]2[C:15]([C:16]([O:18][CH2:19][C:20]3[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=3)=[O:17])=[C:11]([C:8]3[S:7][C:6]4=[C:5]([S:36]([CH3:37])=[O:46])[N:4]=[C:3]([S:2][CH3:1])[N:10]4[CH:9]=3)[C@H:12]([CH3:35])[C@H:13]12)[CH3:32]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1nc(SC)n2cc(C3=C(C(=O)OCc4ccc([N+](=O)[O-])cc4)N4C(=O)[C@H]([C@@H](C)O)[C@H]4[C@H]3C)sc12
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CSc1nc(S(C)=O)c2sc(C3=C(C(=O)OCc4ccc([N+](=O)[O-])cc4)N4C(=O)[C@H]([C@@H](C)O)[C@H]4[C@H]3C)cn12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 67.4 %

Procedure:
4-Nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (140 mg) was dissolved in 2.5 ml, of dichloromethane. m-Chloroperbenzoic acid (56 mg) was added to the solution. The mixture was stirred at room temperature for 15 min. An aqueous sodium thiosulfate solution (56 ml) was added thereto, followed by separation. The organic layer was washed with 10 ml of a semisaturated aqueous sodium hydrogencarbonate solution and 10 ml of semisaturated brine and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1) to give 97 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(7-methanesulfinyl-5-methylthioimidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate (a mixture of diastereomers).
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:6]=[C:7]([C:13]#[N:14])[C:8](=[CH:11][CH:12]=1)[C:9]#[N:10].[C:19](OC(=O)C)(=[O:21])[CH3:20]>>[C:13]([C:7]1[CH:6]=[C:5]([CH:12]=[CH:11][C:8]=1[C:9]#[N:10])[O:4][C:3]1[CH:15]=[CH:16][CH:17]=[CH:18][C:2]=1[NH:1][C:19](=[O:21])[CH3:20])#[N:14]
Reactant: N#Cc1ccc(Oc2ccccc2N)cc1C#N
Reactant: CC(=O)OC(C)=O
Product: CC(=O)Nc1ccccc1Oc1ccc(C#N)c(C#N)c1

Procedure:
4-(2-Aminophenoxy)phthalonitrile (0.54 g, 2.3 mmol) was stirred in acetic acid anhydride (20 ml) at room temperature for 1 hour. The reaction mixture was poured into crushed ice. The precipitate was filtered off and washed with water and dried in vacuo to give N-[2-(3,4-dicyanophenoxy)phenyl]acetamide as white crystals (yield: 0.57 g, (89%)). Mp: 152.2-153.7° C.
Reaction SMILES: [C:1]([NH:11][C@H:12]([C:15]([OH:17])=[O:16])[CH2:13]Cl)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[OH-].[Na+].[C:20]1([SH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>O>[C:1]([NH:11][C@H:12]([C:15]([OH:17])=[O:16])[CH2:13][S:26][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: Sc1ccccc1
Reactant: O=C(N[C@@H](CCl)C(=O)O)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(N[C@@H](CSc1ccccc1)C(=O)O)OCc1ccccc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 60.4 %

Procedure:
N-Carbobenzyloxy-β-chloro-L-alanine (0.137 g, 0.53 mmol) was dissolved in 0.68 ml of water and, then, 0.58 ml of 2 N aqueous sodium hydroxide was added. Thereafter, 0.069 g (0.63 mmol) of thiophenol was added dropwise at room temperature in a nitrogen gas atmosphere. After 2 hours of stirring at 60° C., the reaction mixture was cooled with ice and acidified with 1 N hydrochloric acid, and then extracted with ethyl acetate. The solvent was distilled off and the residue was purified by column chromatography to give 0.107 g (0.32 mmol, 61%) of N-carbobenzyloxy-S-phenyl-L-cysteine. The product obtained had an optical purity of not less than 98% e.e. as determined by HPLC analysis in the same manner as in Example 13.