Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1C(=O)N(O[C:9]([O:11][N:12]2[C:17](=[O:18])[CH2:16][CH2:15][C:13]2=[O:14])=[O:10])C(=O)C1.[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(#N)C>[CH2:19]([NH:26][C:9](=[O:10])[O:11][N:12]1[C:13](=[O:14])[CH2:15][CH2:16][C:17]1=[O:18])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(ON1C(=O)CCC1=O)ON1C(=O)CCC1=O
Reactant: NCc1ccccc1
Solvent: CC#N
Product: O=C(NCc1ccccc1)ON1C(=O)CCC1=O
Temperature: 25 °C
Yield: 76.2 %

Procedure:
18.4 g of N,N'-disuccinimidyl carbonate are added in small portions at 5° C. within 5 minutes to a solution of 6.4 g of benzylamine in 150 ml of acetonitrile. The reaction mixture is stirred at room temperature and then evaporated. The residue is taken up in ethyl acetate and washed with water. The organic phase is dried, concentrated and the residue is recrystallized from methylene chlorideohexane. 11.3 g of colourless 2,5-dioxo-pyrrolidin-1-yl benzylcarbamate, MS (FAB): 133 (M- HO-Succ), are isolated.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)=O.[NH2:15][C@H:16]([C:19]([OH:21])=[O:20])[CH2:17][SH:18]>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[NH:15][CH:16]([C:19]([OH:21])=[O:20])[CH2:17][S:18]1
Reactant: O=C(c1ccccn1)c1ccccn1
Reactant: N[C@@H](CS)C(=O)O
Solvent: CCO
Product: O=C(O)C1CSC(c2ccccn2)(c2ccccn2)N1
Yield: 11 %

Procedure:
A mixture of 3.68 g of di-2-pyridyl ketone, 2.42 g of L-cysteine, 25 ml of ethanol was refluxed for 3.5 hours. After allowing the mixture to cool, the insoluble matter was filtered off, and the filtrate was concentrated to dryness under reduced pressure. The residue was washed in sequence with ethyl acetate and ether to give 0.63 g of 2,2-di(2-pyridyl)-thiazolidine-4-carboxylic acid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[CH3:12])[N:5]=[C:4]([CH3:13])[N:3]=1.[CH3:14][O:15][CH:16]([O:19][CH3:20])[CH2:17][NH2:18]>O1CCCC1>[CH3:14][O:15][CH:16]([O:19][CH3:20])[CH2:17][NH:18][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[CH3:12])[N:5]=[C:4]([CH3:13])[N:3]=1
Reactant: Cc1nc(Cl)c2c(C)cccc2n1
Reactant: COC(CN)OC
Solvent: C1CCOC1
Product: COC(CNc1nc(C)nc2cccc(C)c12)OC
Temperature: 5 °C

Procedure:
4. 14.15 g of crude 4-chloro-2,5-dimethylquinazoline are suspended in 300 ml of tetrahydrofuran, cooled to 5° C. and treated with 16.5 ml of 2,2-dimethoxyethylamine while stirring. The mixture is stirred at room temperature for 24 h., a further 10 ml of 2,2-dimethoxyethylamine are added thereto and the mixture is stirred for a further 40 h. The reaction mixture is evaporated in vacuum and the residue is partitioned between chloroform and saturated aqueous sodium hydrogen carbonate solution. The chloroform solution is evaporated in a vacuum. The residue (21 g) is chromatographed over 150 g of silica gel. 1.85 g of 4-(2,2-dimethoxyethylamino)-2,5-dimethylquinozoline are eluted with ethyl acetate. These are recrystallized from hexane. There are obtained 18.3 g of 4-(2,2-dimethoxyethyl-amino)-2,5-dimethylquinazoline of m.p. 48°-49° C.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]2[O:17][CH3:18])[C:3]=1[C:4]#[N:5].O=[C:20]([CH3:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>>[NH2:5][C:4]1[C:3]2[C:2](=[CH:9][CH:8]=[CH:7][C:6]=2[O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]2[O:17][CH3:18])[N:1]=[C:20]([CH3:27])[C:21]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: CCOC(=O)CC(C)=O
Reactant: COC1CCCCC1Oc1cccc(N)c1C#N
Product: CCOC(=O)c1c(C)nc2cccc(OC3CCCCC3OC)c2c1N

Procedure:
Prepared as in Example 2a from 2-Amino-6-(2-methoxycyclohexyloxy)benzonitrile (Example 109b) and ethyl 3-oxobutanoate as a pale yellow oil (16%). MS 359 (MH+).
Reaction SMILES: C1([O:7][C:8](=O)[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]4([C:38](=[O:47])[NH:39][C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=5)[CH2:37][CH2:36]4)=[O:34])=[CH:28][C:27]=3[F:48])[CH:22]=[CH:21][N:20]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1.Cl.Cl.[N:52]1([CH2:56][CH:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)[CH2:55][CH2:54][CH2:53]1.C(N(CC)CC)C>CN(C)C=O>[N:52]1([CH2:56][CH:57]2[CH2:62][CH2:61][N:60]([C:8]([NH:9][C:19]3[CH:24]=[C:23]([O:25][C:26]4[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]5([C:38]([NH:39][C:40]6[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=6)=[O:47])[CH2:37][CH2:36]5)=[O:34])=[CH:28][C:27]=4[F:48])[CH:22]=[CH:21][N:20]=3)=[O:7])[CH2:59][CH2:58]2)[CH2:55][CH2:54][CH2:53]1
Reactant: O=C(Oc1ccccc1)N(C(=O)Oc1ccccc1)c1cc(Oc2ccc(NC(=O)C3(C(=O)Nc4ccc(F)cc4)CC3)cc2F)ccn1
Reactant: C1CN(CC2CCNCC2)C1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(Nc1cc(Oc2ccc(NC(=O)C3(C(=O)Nc4ccc(F)cc4)CC3)cc2F)ccn1)N1CCC(CN2CCC2)CC1
Reaction time: 3 h
Yield: 92.3 %

Procedure:
To a solution of [4-(2-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (50 mg) in N,N-dimethylformamide (1.0 ml) were added 4-(azetidin-1-ylmethyl)piperidine dihydrochloride (69 mg) and triethylamine (0.085 ml) at room temperature, followed by stirring for 3 hr. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous solution of ammonium chloride and brine in this order, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the titled compound were concentrated under reduced pressure. A solid was precipitated by addition of diethyl ether:heptane=1:3 to the resultant residue. The solvent was removed under reduced pressure. The solid residue was dried under reduced pressure to provide the titled compound as white powder (42.0 mg, 92%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[Br:12]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl>[Br:12][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[C:9]([OH:11])=[O:10]
Reactant: O=C1CCC(=O)N1Br
Reactant: O=C(O)Cc1ccc(F)cc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(O)C(Br)c1ccc(F)cc1

Procedure:
A solution of 4-fluorophenylacetic acid (9.7 g), N-bromosuccinimide (11.2 g) and azobisisobutyronitrile (AIBN, 0.2 g) in carbontetrachloride (100 ml) was reluxed for 2 hours. After cooling it was filtered through Celite® and the filtrate was evaporated to give an oily residue of α-bromo-4-fluorophenylacetic acid, which was used for next step without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[N:14]=[C:15]([OH:23])[C:16]3[CH:17]=[CH:18][CH:19]=[N:20][C:21]=3[CH:22]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].O[C@H:25]([C@H:27]1[CH2:31][N:30]([C@H:32]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[CH3:33])[C:29](=[O:42])[CH2:28]1)[CH3:26].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[CH3:41][O:40][C:37]1[CH:38]=[CH:39][C:34]([C@@H:32]([N:30]2[CH2:31][C@H:27]([C@H:25]([O:23][C:15]3[N:14]=[C:13]([C:5]4[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=4)[CH:22]=[C:21]4[C:16]=3[CH:17]=[CH:18][CH:19]=[N:20]4)[CH3:26])[CH2:28][C:29]2=[O:42])[CH3:33])=[CH:35][CH:36]=1
Reactant: COc1cc(-c2cc3ncccc3c(O)n2)cc(OC)c1OC
Reactant: COc1ccc([C@H](C)N2C[C@H]([C@H](C)O)CC2=O)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccc([C@H](C)N2C[C@H]([C@@H](C)Oc3nc(-c4cc(OC)c(OC)c(OC)c4)cc4ncccc34)CC2=O)cc1
Temperature: 0 °C
Reaction time: 3.5 h

Procedure:
114.6 g of powdered 7-(3,4,5-trimethoxy-phenyl)-[1.6]naphthyridine-5-ol is suspended in 900 mL tetrahydrofurane. A solution of 115.9 g of (R)-4-[(S)-1-hydroxyethyl]-1-[(S)-1-(4-methoxyphenyl)-ethyl]-pyrrolidin-2-one and 136 g triphenylphosphine in 1000 mL tetrahydrofurane is added. The suspension is cooled to 0° C. During 40 minutes a solution of 105 mL diisopropylazodicarboxylate [DIAD] in 400 mL tetrahydrofurane is added at 0° C. to 2° C. The suspension is stirred for 3.5 hours at this temperature and then warmed up to 20° C. The solvent is evaporated under reduced pressure. The residue is suspended in 680 mL of tert-butylmethylether. Seeding crystalls of triphenylphosphinoxid are added and the mixture is stirred 16 hours at 20° C. The precipitate is filtered and washed with tert.-butylmethylether. The filtrate is evaporated under reduced pressure. The crude product is dissolved in a mixture of 220 mL of 2-propanol and 1100 mL of isopropyl acetate at 40° C. 48 mL of trimethylchlorosilane are added during 15 minutes. The suspension is stirred for 2 hours at 20° C. The precipitate is filtered and washed with isopropyl acetate and dried at 60° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[C:11]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)=[C:19]([C:29]#[N:30])[CH:18]=3)=[O:15])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Br[CH2:32][CH2:33][CH2:34][OH:35].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[C:11]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:24][CH2:25][N:26]([CH2:32][CH2:33][CH2:34][OH:35])[CH2:27][CH2:28]4)=[C:19]([C:29]#[N:30])[CH:18]=3)=[O:15])[CH:10]=[N:9]2)=[CH:4][CH:3]=1
Reactant: Cc1c(C(=O)Nc2ccc(N3CCNCC3)c(C#N)c2)cnn1-c1ccc(Cl)cc1
Reactant: OCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1c(C(=O)Nc2ccc(N3CCN(CCCO)CC3)c(C#N)c2)cnn1-c1ccc(Cl)cc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 54.9 %

Procedure:
1-(4-Chlorophenyl)-N-[3-cyano-4-(piperazin-1-yl)phenyl]-5-methylpyrazole-4-carboxamide (4.0 g), 3-bromopropanol (1.6 g) and potassium carbonate (1.6 g) were added to dimethylformamide (25 ml) and the mixture was stirred at 60° C. for 3 h. The reaction mixture was added into water, and the obtained crystals were recrystallized from hydrous dimethylformamide to give the title compound (2.5 g), melting point: 213° C.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O-:17])(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[C:1]([O:17][C:9](=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccccc1
Reactant: O=C([O-])c1ccccc1
Product: O=C(OC(=O)c1ccccc1)c1ccccc1

Procedure:
The synthesis of tetratelluride catalysts based on dendritic wedge 3 is shown in FIG. 15. Benzyl alcohol 16 (Francavilla et al., J. Am. Chem. Soc., 123:57 et al. (2001), which is hereby incorporated by reference in its entirety) was converted to the benzoate 17 in 93% isolated yield with benzoic anhydride as previously described. The four silyl groups were removed with HF-pyridine to give tetraol 18 in 88% isolated yield. As before, the hydroxyl groups were converted via the mesylate to the corresponding bromides (Wendler et al., Tetrahedron, 3:144 et al. (1958), which is hereby incorporated by reference in its entirety) to give tetrabromide 19 in 52% overall yield. The addition of excess PhTeNa to 19 gave tetratelluride 20a in 65% isolated yield; 4-Me2NC6HTeNa, tetratelluride 20b in 92% isolated yield; and n-C6H13TeNa, tetratelluride 20c in 51% isolated yield.
Reaction SMILES: [CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=[C:13]4I)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:32]=[N:31][CH:30]=[C:29]([Sn](CCCC)(CCCC)CCCC)[N:28]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:26][C:27]1[N:28]=[C:29]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:8]4[CH:7]=[N:6][CH:5]=[C:4]([CH:1]5[CH2:3][CH2:2]5)[N:9]=4)[CH:11]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=2)[CH:30]=[N:31][CH:32]=1
Reactant: Ic1nn(C2CCCCO2)c2ccc(-c3cncc(C4CC4)n3)cc12
Reactant: CCCC[Sn](CCCC)(CCCC)c1cncc(Cl)n1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: Clc1cncc(-c2nn(C3CCCCO3)c3ccc(-c4cncc(C5CC5)n4)cc23)n1
Temperature: 105 °C
Yield: 35.5 %

Procedure:
A glass microwave reaction vessel was charged with 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol), 2-chloro-6-(tributylstannyl)pyrazine (190 mg, 0.47 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) and CuI (6 mg, 0.031 mmol) in DMF (1 mL). Argon was bubbled through the mixture for 5 min. The tube was sealed and the mixture was heated to 105° C. for 2 h. The reaction was diluted with EtOAc and water and filtered through celite. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (48 mg, 0.11 mmol, 35% yield) as a light-yellow solid. MS (ESI, pos. ion) m/z: 433.0 (M+1).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH3:16])[CH:12]=3)[CH:7]=[C:6]2[C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)[CH2:3][CH2:2]1.[I:26]N1C(=O)CCC1=O>CN(C=O)C.O>[CH:1]1([CH2:4][N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH3:16])[CH:12]=3)[C:7]([I:26])=[C:6]2[C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[CH2:3][CH2:2]1
Reactant: O=C1CCC(=O)N1I
Reactant: CCOc1ccc2cc(-c3ccc([N+](=O)[O-])cc3)n(CC3CC3)c2c1
Solvent: CN(C)C=O
Solvent: O
Product: CCOc1ccc2c(I)c(-c3ccc([N+](=O)[O-])cc3)n(CC3CC3)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.4 %

Procedure:
To 1-cyclopropylmethyl-6-ethoxy-2-(4-nitro-phenyl)-1H-indole (800 mg, 2.38 mmol) in DMF (8.6 mL) at room temperature was added a solution of N-iodosuccinimide (585 mg, 2.6 mmol) in DMF (5.6 mL) dropwise. The reaction mixture was stirred at room temperature for 2 h, diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O, and then with sat. aq. NaHCO3 and then dried and concentrated. The residue was triturated with hexane to provide 1-cyclopropylmethyl-6-ethoxy-3-iodo-2-(4-nitro-phenyl)-1H-indole (1.061 g, 96%) as an orange solid.
Reaction SMILES: [CH2:1]([N:8]1[C:12](=[O:13])[N:11]([CH2:14][CH2:15][O:16]C(=O)C2C=CC=CC=2)[C:10](=[O:25])[S:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(OCC)(=O)C>CO>[CH2:1]([N:8]1[C:12](=[O:13])[N:11]([CH2:14][CH2:15][OH:16])[C:10](=[O:25])[S:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCCn1c(=O)sn(Cc2ccccc2)c1=O)c1ccccc1
Agent: Cl
Solvent: CO
Solvent: CCOC(C)=O
Product: O=c1sn(Cc2ccccc2)c(=O)n1CCO
Temperature: 50 °C
Reaction time: 84 h
Yield: 81.1 %

Procedure:
To a suspension of benzoic acid 2-(2-benzyl-3,5-dioxo-[1,2,4]thiadiazolidin-4-yl)ethyl ester (74.0 g, 207.6 mmol) in methanol (740 mL) 12N HCl (740 mL) was added at room temperature. The mixture was heated at 50° C. for 18 h, then additional 12N HCl (250 mL) was added and the mixture was stirred for 84 hours at 40° C. until hydrolysis was completed. The mixture was concentrated at reduced pressure to remove the methanol, and the resulting mixture was extracted with methylene chloride (3×500 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated to yield an oil that was treated with hot ethyl acetate (200 mL) and precipitated by the addition of n-heptane (200 mL) to yield the pure desired product as a white solid (42.5 g, 81%)
Reaction SMILES: [O:1]1[CH2:5][CH2:4][C@@H:3]([OH:6])[CH2:2]1.CCN(CC)CC.[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1>C(Cl)Cl>[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([O:6][C@H:3]2[CH2:4][CH2:5][O:1][CH2:2]2)(=[O:23])=[O:22])=[CH:17][CH:16]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O[C@@H]1CCOC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)O[C@H]2CCOC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.9 %

Procedure:
To a solution of (R)-tetrahydrofuran-3-ol (3 g, 34.1 mmole) and Et3N (6.9 g, 68.2 mmole) in DCM (40 mL) at 0° C. was added 4-methylbenzene-1-sulfonyl chloride (7.2 g, 37.5 mmole). The mixture was stirred at room temperature for 8 h. The mixture was washed with water, dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 15% ethyl acetate in hexane) to give the title compound (6.6 g, 80% yield). MS (ESI) m/z: Calc. 242.1 (M+). Found: 243.1 (M++1).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[CH:5]([C@H:7]1[C@@H:12]2[O:13]S(=O)O[C@@H:11]2[CH:10]=[C:9]([C:17]([O:19][CH3:20])=[O:18])[CH2:8]1)=[CH2:6]>CN(C=O)C.CCOC(C)=O>[N:1]([C@@H:11]1[C@@H:12]([OH:13])[C@H:7]([CH:5]=[CH2:6])[CH2:8][C:9]([C:17]([O:19][CH3:20])=[O:18])=[CH:10]1)=[N+:2]=[N-:3]
Reactant: C=C[C@@H]1CC(C(=O)OC)=C[C@H]2OS(=O)O[C@@H]12
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C=C[C@@H]1CC(C(=O)OC)=C[C@H](N=[N+]=[N-])[C@H]1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Sodium azide can be added to a solution of Example 17G in DMF. The reaction mixture can be stirred overnight at room temperature, diluted with EtOAc, washed with brine, dried (MgSO4), filtered and concentrated. The concentrate can be purified by flash column chromatography to afford the desired product.
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](O)=[O:22])=[C:11]3[N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([S:31]([C:34]2[CH:35]=[C:36]([NH2:40])[CH:37]=[CH:38][CH:39]=2)(=[O:33])=[O:32])[CH2:27][CH2:26]1>>[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([S:31]([C:34]2[CH:35]=[C:36]([NH:40][C:21]([C:20]3[CH:19]=[N:18][N:12]4[C:13]([CH:15]([F:16])[F:17])=[CH:14][C:9]([C:4]5[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=5)=[N:10][C:11]=34)=[O:22])[CH:37]=[CH:38][CH:39]=2)(=[O:33])=[O:32])[CH2:27][CH2:26]1
Reactant: O=C(O)c1cnn2c(C(F)F)cc(-c3ccc(Cl)c(Cl)c3)nc12
Reactant: CN1CCN(S(=O)(=O)c2cccc(N)c2)CC1
Product: CN1CCN(S(=O)(=O)c2cccc(NC(=O)c3cnn4c(C(F)F)cc(-c5ccc(Cl)c(Cl)c5)nc34)c2)CC1

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) and 3-(4-methyl-piperazine-1-sulfonyl)-phenylamine [CAS 436095-35-1] according to general procedure II. Yellow solid. MS (ISP) 595.3 [(M+H)+]; mp 229° C.
Reaction SMILES: [N:1]([C:4]1[CH2:5][C@@H:6]2[CH2:23][C:22](=[O:24])[N:7]2[C:8]=1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1)=[O:10])=[N+:2]=[N-:3].[CH2:25]([N:27]([CH2:31][CH3:32])[C:28]#[C:29][CH3:30])[CH3:26]>ClCCl>[CH2:25]([N:27]([CH2:31][CH3:32])[C:28]1[N:1]([C:4]2[CH2:5][C@@H:6]3[CH2:23][C:22](=[O:24])[N:7]3[C:8]=2[C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([N+:19]([O-:21])=[O:20])=[CH:17][CH:18]=2)=[O:10])[N:2]=[N:3][C:29]=1[CH3:30])[CH3:26]
Reactant: [N-]=[N+]=NC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)C[C@H]2C1
Reactant: CC#CN(CC)CC
Solvent: ClCCl
Product: CCN(CC)c1c(C)nnn1C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)C[C@H]2C1
Yield: 15.1 %

Procedure:
A stirred, 0° C. solution of p-nitrobenzyl 2-azido-carbapen-2-em-3-carboxylate (5.9 mg, 18 micromol) in dry dichloromethane (0.30 ml) was treated with 1-diethylaminopropyne (2.5 microliter, 2.0 mg, 18 micromol). After 1.25 hours the mixture was filtered through a 6 cm×4 mm column of florisil and the eluate was evaporated under vacuum. The residue was chromatographed on one 5 cm×20 cm 250 micron silica gel thin layer chromatography plate developed with 5:1 (v/v) dichloromethane-ethyl acetate, and the band centered at Rf 0.30 was eluted with ethyl acetate. The eluate was evaporated under vacuum to provide 1.2 mg (15%) p-nitrobenzyl 2-(5-diethylamino-4-methyl-1,2,3-triazol-1-yl)-carbapen-2-em-3-carboxylate; IR (CH2Cl2): 1785, 1730 cm-1 ; NMR (CDCl3): δ 0.92 t (J=7 Hz, 6H), 2.30 s (3H), 2.97 q (J=7 Hz, 4H), 3.18 dd (J1 =4 Hz, J2 =17 Hz, 1H), 3.24 dd (J1 =10 Hz, J2 =18 Hz, 1H), 3.40 dd (J1 =8 Hz, J2 =18 Hz, 1H), 3.65 dd (J1 =6 Hz, J2 =17 Hz, 1H), 4.25 m (1H), 5.22 d (J=14 Hz, 1H), 5.32 d (J=14 Hz, 1H), 7.45 d (J=9 Hz, 2H), 8.22 d (J=9 Hz); MS (m/e): 440, 414, 412, 398, 384, 369, 357, 355, 341, 333.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([CH3:9])=[CH:4][CH:3]=1.[CH:10]([C:13]1[CH:14]=[CH:15][C:16]2[C:21]([NH:22][C:23]3[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=3[S:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)[C:26](Cl)=[O:27])=[N:20][CH:19]=[N:18][C:17]=2[N:41]=1)([CH3:12])[CH3:11].C(N(CC)CC)C>ClCCl>[OH:8][C:6]1[CH:7]=[C:2]([NH:1][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:31]([S:32][C:33]3[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=3)=[C:23]([NH:22][C:21]3[C:16]4[CH:15]=[CH:14][C:13]([CH:10]([CH3:11])[CH3:12])=[N:41][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:24]=2)[CH:3]=[CH:4][C:5]=1[CH3:9]
Reactant: Cc1ccc(N)cc1O
Reactant: COc1ccc(Sc2ccc(C(=O)Cl)cc2Nc2ncnc3nc(C(C)C)ccc23)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(Sc2ccc(C(=O)Nc3ccc(C)c(O)c3)cc2Nc2ncnc3nc(C(C)C)ccc23)cc1
Reaction time: 18 h
Yield: 60.2 %

Procedure:
A solution of 5-amino-o-cresol (20.4 mg, 0.1655 mmol) and the product from Example 14B (70 mg, 0.1655 mmol) in dichloromethane (4 mL) was treated with triethylamine (0.025 mL, 0.1806 mmol) at room temperature. The resulting solution was stirred for 18 hours. The reaction mixture was then washed with water and brine, and the combined organic layers were dried over MgSO4, the concentrated under vacuum to give a residue which was purified by silica gel chromatography using methanol and dichloromethane as eluent to provide the title compound (55 mg, 65%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.34 (d, J=6.99 Hz, 6H), 2.07 (s, 3H), 3.17-3.28 (m, 1H), 3.77 (s, 3H), 6.86-7.10 (m, 5H), 7.30-7.46 (m, 3H), 7.64 (d, J=7.35 Hz, 1H), 7.72-7.86 (m, 1H), 7.95 (s, 1H), 8.43-8.68 (m, 1H), 8.77-8.97 (m, 1H), 9.27-9.46 (m, 1H), 10.02 (s, 1H), 10.21-10.40 (m, 1H); MS (APCI) m/z 552 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13](=[O:15])[CH3:14])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH3:16][O:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([CH:27]=O)=[CH:23][NH:24]2)=[CH:20][CH:19]=1>>[CH3:16][O:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22](/[CH:27]=[CH:14]/[C:13]([C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)=[O:15])=[CH:23][NH:24]2)=[CH:20][CH:19]=1
Reactant: COc1cc(C(C)=O)cc(OC)c1OC
Reactant: COc1ccc2c(C=O)c[nH]c2c1
Product: COc1ccc2c(/C=C/C(=O)c3cc(OC)c(OC)c(OC)c3)c[nH]c2c1
Yield: 32 %

Procedure:
Substantially the same procedure as in Example 1 was repeated using 3',4',5'-trimethoxyacetophenone (659 mg) and 6-methoxyindole-3-carboxaldehyde (550 mg) except that the reaction solution was concentrated under reduced pressure, that the residue was purified by silica gel column chromatography, and that the obtained crude crystals were recrystallized from ethanol, to give Compound 39 (369 mg).