Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[CH2:20][CH2:19][C@H:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23](Br)[CH:22]=3)[C@H:17]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:16]2)=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:36][O:37][CH2:38][CH2:39][NH2:40]>>[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]([N:15]2[CH2:20][CH2:19][C@H:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([NH:40][CH2:39][CH2:38][O:37][CH3:36])[CH:22]=3)[C@H:17]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:16]2)=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: COCCN
Reactant: O=C(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)N1CC[C@H](c2cccc(Br)c2)[C@H](c2ccccc2)C1
Product: COCCNc1cccc([C@H]2CCN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)C[C@H]2c2ccccc2)c1

Procedure:
The title compound, MS: m/e=551.1 (M+), was prepared in accordance with the general method of example 10 from rac-cis-(3,5-bis-trifluoromethyl-phenyl)-[4-(3-bromo-phenyl)-3-phenyl-piperidin-1-yl]-methanone and 2-methoxy ethylamine.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[CH:17]=[CH:18][C:19]([F:34])=[C:20]([NH:22][S:23]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=3[F:33])(=[O:25])=[O:24])[CH:21]=2)[CH:5]=[CH:4][N:3]=1.[O:35]1[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37][CH2:36]1>C1COCC1>[F:33][C:27]1[CH:28]=[CH:29][C:30]([F:32])=[CH:31][C:26]=1[S:23]([NH:22][C:20]1[CH:21]=[C:16]([C:9]2[N:10]=[C:11]([CH:13]([CH3:15])[CH3:14])[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:41][CH:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)[N:7]=2)[CH:17]=[CH:18][C:19]=1[F:34])(=[O:25])=[O:24]
Reactant: CC(C)c1nc(-c2ccc(F)c(NS(=O)(=O)c3cc(F)ccc3F)c2)c(-c2ccnc(Cl)n2)s1
Reactant: NC1CCOCC1
Solvent: C1CCOC1
Product: CC(C)c1nc(-c2ccc(F)c(NS(=O)(=O)c3cc(F)ccc3F)c2)c(-c2ccnc(NC3CCOCC3)n2)s1

Procedure:
Following a procedure analogous to the procedure described in Example 1 using N-{5-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (0.10 g, 0.19 mmol) and tetrahydro-2H-pyran-4-amine (0.19 g, 1.90 mmol) in THF (1 mL) the title compound was obtained as an off-white solid (0.094 g, 0.16 mmol, 84% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.02 (d, J=5.2 Hz, 1H), 7.75-7.65 (m, 1H), 7.55-7.38 (m, 1H), 7.38-7.28 (m, 1H), 7.28-7.11 (m, 3H), 7.11-6.88 (m, 2H), 6.22 (d, J=5.2 Hz, 1H), 5.06 (d, J=7.8 Hz, 1H), 4.02-3.92 (m, 4H), 3.56-3.46 (m, 2H), 3.29 (quin, J=6.9 Hz, 1H), 2.00 (d, J=13.2 Hz, 2H), 1.41 (d, J=7.0 Hz, 6H). MS (ESI): 590 [M+H]+.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](Cl)=[N:4][N:3]=1.[C:13]1([P:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:20]C)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>ClC1C=CC=CC=1Cl>[C:13]1([P:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([P:19]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:20])=[N:4][N:3]=2)=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: COP(c1ccccc1)c1ccccc1
Reactant: Clc1nnc(Cl)c2ccccc12
Solvent: Clc1ccccc1Cl
Product: O=P(c1ccccc1)(c1ccccc1)c1nnc(P(=O)(c2ccccc2)c2ccccc2)c2ccccc12
Reaction time: 312 h

Procedure:
To a stirred, refluxing mixture of 5.00 g of 1,4-dichlorophthalazine in 50 ml of o-dichlorobenzene under nitrogen was added dropwise 15.00 of methyl diphenylphosphinite. After the addition was completed, the mixture was refluxed for 6 hours and then allowed to stand at room temperature for 13 days. The resulting solid was separated by filtration, washed with benzene and with hexane, recrystallized from 125 ml of toluene with decolorizing charcoal treatment, and dried at 100° C./0.1 mm (13 Pa) to give 6.41 g of 1,4-bis(diphenylphosphinyl)phthalazine (shown by formula in Claim 13) as a light-yellow solid, mp 225°-228.5° C. Anal. Calcd C32H24N2O2P2 : C, 72.45; H, 4.56; N, 5.28; P, 11.68. Found: C, 72.49; H, 4.62; N, 5.36; P, 11.95.
Reaction SMILES: [CH3:1][N:2]=[C:3]([NH2:9])[NH:4][C:5](=[N:7][CH3:8])[NH2:6].CC(C)([O-])C.[K+].[Cl-].[Zn+2:17].[Cl-]>O.C(O)(C)(C)C.C(OCC)C>[Zn:17].[CH3:1][N:2]=[C:3]([NH2:9])[NH:4][C:5](=[N:7][CH3:8])[NH2:6]
Reactant: [Zn+2]
Agent: CC(C)(C)[O-]
Agent: CN=C(N)NC(N)=NC
Agent: [Cl-]
Solvent: CC(C)(C)O
Solvent: O
Solvent: CCOCC
Product: [Zn]
Reaction time: 0.17 h

Procedure:
Dimethylbiguanide (33 mg) was dissolved in 1 mL of water, after which 0.44 mL of 1 M potassium t-butoxide in t-butanol was added and the solution stirred for 10 minutes. Zinc chloride in diethyl ether (0.22 mL of 1M solution) was added and the solution stirred for 5 hours. The resultant precipitant was separated from the liquid by centrifuging at 8,000 rpm for 6 minutes and the supernatant was decanted. The pellet was washed by adding 1 mL of water, vortex mixed, centrifuged and the supernatant decanted. After an overnight drying under high vacuum the yield was 20 mg of a free flowing white powder which contained no organic material by 1H NMR. The isolated product was zinc salts in various hydrated forms.
Reaction SMILES: [CH3:1][C:2]1[C:6]([NH:7][CH:8]([CH3:21])[CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)=[C:5]([C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[O:4][N:3]=1.[CH2:37]([O:39][C:40](=[O:50])[C:41]#[C:42][C:43]1[CH:48]=[CH:47][C:46](Br)=[CH:45][CH:44]=1)[CH3:38]>>[CH2:37]([O:39][C:40](=[O:50])[C:41]#[C:42][C:43]1[CH:48]=[CH:47][C:46]([C:25]2[CH:26]=[CH:27][C:22]([C:5]3[O:4][N:3]=[C:2]([CH3:1])[C:6]=3[NH:7][CH:8]([CH3:21])[CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:19])([F:20])[F:18])[CH:12]=3)=[CH:23][CH:24]=2)=[CH:45][CH:44]=1)[CH3:38]
Reactant: Cc1noc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c1NC(C)CCc1cccc(C(F)(F)F)c1
Reactant: CCOC(=O)C#Cc1ccc(Br)cc1
Product: CCOC(=O)C#Cc1ccc(-c2ccc(-c3onc(C)c3NC(C)CCc3cccc(C(F)(F)F)c3)cc2)cc1

Procedure:
Prepared according to the procedure described in Example 1, Step 7, using {3-methyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-isoxazol-4-yl}-[1-methyl-3-(3-trifluoromethyl-phenyl)-propyl]-amine and (4-bromo-phenyl)-propynoic acid ethyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:27])[C:7]=1[NH:8][C:9]1[NH:10][C:11]2[C:17]3[CH2:18][C:19]([CH3:22])([CH3:21])[O:20][C:16]=3[C:15]([C:23]([O:25]C)=O)=[CH:14][C:12]=2[N:13]=1.[F:28][C:29]1[C:35]([F:36])=[C:34]([F:37])[CH:33]=[CH:32][C:30]=1[NH2:31].C[Al](C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:27])[C:7]=1[NH:8][C:9]1[NH:10][C:11]2[C:17]3[CH2:18][C:19]([CH3:21])([CH3:22])[O:20][C:16]=3[C:15]([C:23]([NH:31][C:30]3[CH:32]=[CH:33][C:34]([F:37])=[C:35]([F:36])[C:29]=3[F:28])=[O:25])=[CH:14][C:12]=2[N:13]=1
Reactant: COC(=O)c1cc2nc(Nc3c(Cl)cncc3Cl)[nH]c2c2c1OC(C)(C)C2
Reactant: Nc1ccc(F)c(F)c1F
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Product: CC1(C)Cc2c(c(C(=O)Nc3ccc(F)c(F)c3F)cc3nc(Nc4c(Cl)cncc4Cl)[nH]c23)O1
Yield: 58.6 %

Procedure:
The title compound was prepared following the procedure described for Example-137 by using methyl 2-[(3,5-dichloropyridin-4-yl)amino]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxylate (Step-1 of Intermediate-3, 0.100 g, 0.245 mmol), 2,3,4-trifluoroaniline (0.078 g, 0.530 mmol), trimethyl aluminium (2M solution in toluene) (0.5 mL), dry toluene (5.0 mL) at room temperature to afford 0.075 g of the desired product. 1HNMR (DMSO-d6): δ 1.57 (s, 6H), 3.09 (s, 2H), 7.28-7.39 (m, 2H), 8.15 (m, 1H), 8.45 (s, 2H), 9.92 (s, 1H), 11.02 (br s, 1H), 11.58 (br s, 1H); MS [M+H]+: 521.93.
Reaction SMILES: [C:1]1([S:7]([N:10]2[CH2:15][CH:14]3[CH:12]([CH:13]3[N:16]3[C:20](=[O:21])[C:19]([CH2:47][C:48]4[N:49]=[CH:50][N:51]([C:53]([C:66]5[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=5)([C:60]5[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=5)[C:54]5[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=5)[CH:52]=4)([CH2:22][C:23]4[N:24]=[CH:25][N:26]([C:28]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH:27]=4)[NH:18][C:17]3=[S:72])[CH2:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:73]([C:75]1[CH:84]=[CH:83][C:78]([C:79](=[O:82])[CH2:80]Br)=[CH:77][CH:76]=1)#[N:74].C[Si]([N-][Si](C)(C)C)(C)C.[K+]>>[C:1]1([S:7]([N:10]2[CH2:15][CH:14]3[CH:12]([CH:13]3[N:16]3[C:20](=[O:21])[C:19]([CH2:47][C:48]4[N:49]=[CH:50][N:51]([C:53]([C:60]5[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=5)([C:66]5[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=5)[C:54]5[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=5)[CH:52]=4)([CH2:22][C:23]4[N:24]=[CH:25][N:26]([C:28]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH:27]=4)[N:18]=[C:17]3[S:72][CH2:80][C:79]([C:78]3[CH:83]=[CH:84][C:75]([C:73]#[N:74])=[CH:76][CH:77]=3)=[O:82])[CH2:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1N(C2C3CN(S(=O)(=O)c4ccccc4)CC32)C(=S)NC1(Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: N#Cc1ccc(C(=O)CBr)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Product: N#Cc1ccc(C(=O)CSC2=NC(Cc3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)(Cc3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)C(=O)N2C2C3CN(S(=O)(=O)c4ccccc4)CC32)cc1

Procedure:
Using the same procedure as described in Example 1C, the title compound of 53C (0.548 g, 0.558 mmol) and 4-cyanophenacyl bromide (138 mg, 0.614 mmol) in the presence of potassium bis(trimethylsilyl)-amide (129 mg, 0.614 mmol) reacted to yield the title compound of 53D, after chromatographic purification, 0.46 g (0.41 mmol, 73% yield).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([C:15](=O)[CH3:16])=[C:13]([OH:18])[C:12]([O:19][C:20]2[C:28]([CH3:29])=[CH:27][C:26]([N+:30]([O-:32])=[O:31])=[C:25]3[C:21]=2[CH2:22][CH2:23][CH2:24]3)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:37][CH2:38][CH3:39])(=[O:36])[NH:34][NH2:35].CCCCCC>C(O)CC>[CH2:1]([O:8][C:9]1[C:14]([C:15](=[N:35][NH:34][C:33]([O:37][CH2:38][CH3:39])=[O:36])[CH3:16])=[C:13]([OH:18])[C:12]([O:19][C:20]2[C:28]([CH3:29])=[CH:27][C:26]([N+:30]([O-:32])=[O:31])=[C:25]3[C:21]=2[CH2:22][CH2:23][CH2:24]3)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)NN
Reactant: CC(=O)c1c(OCc2ccccc2)ccc(Oc2c(C)cc([N+](=O)[O-])c3c2CCC3)c1O
Solvent: CCCCCC
Solvent: CCCO
Product: CCOC(=O)NN=C(C)c1c(OCc2ccccc2)ccc(Oc2c(C)cc([N+](=O)[O-])c3c2CCC3)c1O
Temperature: 75 °C
Reaction time: 8 h
Yield: 64.5 %

Procedure:
To a solution of 1-[6-benzyloxy-2-hydroxy-3-(5-methyl-7-nitroindan-4-yloxy)phenyl]ethanone (1.50 g) in n-propanol (15 mL) was added ethyl carbazate (432 mg). The mixture was stirred under an argon atmosphere at 75° C. overnight and cooled to room temperature. Adding hexane (30 mL), the reaction mixture was stirred for 1 hour. The precipitate was filtrated to give ethyl N′-{1-[6-benzyloxy-2-hydroxy-3-(5-methyl-7-nitroindan-4-yloxy)phenyl]ethylidene}hydrazinecarboxate (1.16 g).
Reaction SMILES: CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:22]=[C:21]2[C:10]([CH2:11][C:12]3[CH:16]=[CH:15][N:14]([CH2:17][C@H:18](O)[CH3:19])[C:13]=32)=[CH:9][CH:8]=1.C(N(CC)CC)C.[N-:30]=[N+:31]=[N-:32].[Na+]>ClCCl.C(OCC)C.CN(C)C=O.O>[N:30]([C@@H:18]([CH3:19])[CH2:17][N:14]1[CH:15]=[CH:16][C:12]2[CH2:11][C:10]3[C:21]([C:13]1=2)=[CH:22][C:7]([Cl:6])=[CH:8][CH:9]=3)=[N+:31]=[N-:32]
Reactant: [N-]=[N+]=[N-]
Reactant: C[C@@H](O)Cn1ccc2c1-c1cc(Cl)ccc1C2
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: O
Product: C[C@@H](Cn1ccc2c1-c1cc(Cl)ccc1C2)N=[N+]=[N-]
Yield: 56.3 %

Procedure:
1.53 ml of methanesulfonyl chloride were added dropwise while stirring to a solution, cooled to 0°, of 2.42 g of (R)-1-(7-chloro-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 5.48 ml of triethylamine in 70 ml of dichloromethane and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 200 ml of diethyl ether, washed twice with 70 ml of saturated sodium hydrogen carbonate solution each time and the combined aqueous phases were extracted once with 70 ml of diethyl ether. The combined organic phases were washed with 70 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The brown oil obtained was dissolved in 50 ml of anhydrous dimethylformamide, treated with 1.27 g of sodium azide and the reaction mixture was heated to 60° for 15 hours while stirring. After cooling, the solution was poured into 140 ml of water and extracted twice with 140 ml of diethyl ether each time and once with 70 ml of ethyl acetate. The combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in a vacuum. The brown oil obtained was purified by column chromatography on silica gel (toluene). 1.5 g (56%) of (S)-1-(2-azido-propyl)-7-chloro-1,4-dihydro-indeno[1,2-b]pyrrole were obtained as an oil.
Reaction SMILES: [Cl:1][CH2:2][C:3]([CH2:5]Cl)=O.[NH2:7][C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][N:9]=1>C(#N)C>[Cl:1][CH2:2][C:3]1[N:7]=[C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][N:9]2[CH:5]=1
Reactant: Cc1ccnc(N)c1
Reactant: O=C(CCl)CCl
Solvent: CC#N
Product: Cc1ccn2cc(CCl)nc2c1
Yield: 23.9 %

Procedure:
A mixture of 1,3-dichloroacetone (30.0 g) and 2-amino-4-picoline (63.9 g) in acetonitrile (210 ml) was refluxed for 1 hour. Evaporation of a solvent gave a residue, which was purified by a column chromatography on silica gel eluting with a mixture of dichloromethane and ethyl acetate (1:1, V/V). The eluted fractions containing the desired product were collected and evaporated in vacuo to give 2-chloromethyl-7-methylimidazo[1,2-a]pyridine (10.21 g).
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:36](=[O:37])[N:13]3[C:14]([C:20]([O:22][CH:23]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[O:21])=[C:15]([OH:19])[CH2:16][S:17](=[O:18])[C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S:38](Cl)([CH3:41])(=[O:40])=[O:39].O>N1C=CC=CC=1>[C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:36](=[O:37])[N:13]3[C:14]([C:20]([O:22][CH:23]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:21])=[C:15]([O:19][S:38]([CH3:41])(=[O:40])=[O:39])[CH2:16][S:17](=[O:18])[C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CS(=O)(=O)Cl
Reactant: O=C(Cc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(O)CS(=O)[C@H]12
Solvent: O
Solvent: c1ccncc1
Product: CS(=O)(=O)OC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)Cc3ccccc3)[C@H]2S(=O)C1
Temperature: 25 °C
Yield: 80.4 %

Procedure:
To a solution of benzhydryl 7-phenylacetamido-3-hydroxy-3-cephem-4-carboxylate-1-oxide (40 g) in pyridine (120 ml) was added mesyl chloride (13 g) under ice-cooling. The reaction mixture was stirred at ambient temperature for an hour. The resulting suspension was poured into water (1 l). The precipitates were collected by filtration, washed with water and methanol, dried under reduced pressure to give benzhydryl 7-phenylacetamido-3-mesyloxy-3-cephem-4-carboxylate-1-oxide (37.0 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([CH3:24])[N:9]=2)[CH:5]=[CH:4][N:3]=1.[C:25]([NH:29][S:30]([C:33]1[S:34][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:36][CH:37]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[C:25]([NH:29][S:30]([C:33]1[S:34][C:35]([C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=4)[CH:11]=[C:10]([CH3:24])[N:9]=3)[CH:5]=[CH:4][N:3]=2)=[CH:36][CH:37]=1)(=[O:31])=[O:32])([CH3:28])([CH3:26])[CH3:27]
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)s1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2ccnc(Cl)c2)n1
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2ccnc(-c3ccc(S(=O)(=O)NC(C)(C)C)s3)c2)n1

Procedure:
The title compound was prepared from 2′-chloro-6-methyl-4-(4-trifluoromethyl-phenyl)-[2,4′]bipyridinyl (example E.28) (0.300 g, 0.86 mmol) and N-tert-butyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-thiophene-2-sulfonamide (example F.1) (0.356 g, 1.029 mmol) according to the general procedure VI. Obtained as a white solid (0.110 g, 24%). MS (ISP) 532.1 [(M+H)+]; mp 225° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[N:3]=1.[Cl:19]N1C(=O)CCC1=O>C(Cl)(Cl)Cl.C(OCC)(=O)C.O>[Cl:19][C:8]1[N:7]2[C:2]([Cl:1])=[N:3][C:4]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=3[Cl:18])=[CH:5][C:6]2=[N:10][CH:9]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: Clc1ccc(-c2cc3nccn3c(Cl)n2)c(Cl)c1
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: Clc1ccc(-c2cc3ncc(Cl)n3c(Cl)n2)c(Cl)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
300 mg (1.0 mmol) of 5-chloro-7-(2,4-dichlorophenyl)imidazo[1,2-c]pyrimidine (Example 6A) are suspended in chloroform (15 ml), 240 mg (1.8 mmol) of N-chlorosuccinimide are added, and the reaction mixture is stirred at RT for 12 h. The reaction mixture is diluted with ethyl acetate (100 ml) and water (75 ml), and the organic phase is separated off, dried over magnesium sulphate and concentrated in a rotary evaporator. The residue is stirred with diethyl ether (20 ml), and the solid is filtered off with suction and dried. 63 mg (18% of theory) of the product are isolated.
Reaction SMILES: N1([C@H]2CCC[C@H]2N)CCCC1.[F:12][CH:13]([F:40])[O:14][C:15]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([O:38][CH3:39])[C:16]=1[C:17]([NH:19][C@H:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:18]>>[F:40][CH:13]([F:12])[O:14][C:15]1[CH:33]=[C:32]([C:34]([F:37])([F:35])[F:36])[CH:31]=[C:30]([O:38][CH3:39])[C:16]=1[C:17]([NH:19][C@@H:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:18]
Reactant: COc1cc(C(F)(F)F)cc(OC(F)F)c1C(=O)N[C@H]1CCC[C@H]1N1CCCC1
Agent: N[C@@H]1CCC[C@@H]1N1CCCC1
Product: COc1cc(C(F)(F)F)cc(OC(F)F)c1C(=O)N[C@@H]1CCC[C@@H]1N1CCCC1

Procedure:
The title compound, light yellow solid, MS: m/e=423.2 [(M+H)+], was prepared in accordance with the general method of example 5 from cis-2-pyrrolidin-1-yl-cyclopentylamine (intermediate Q) and 2-difluoromethoxy-6-methoxy-N-((1S,2R)-2-pyrrolidin-1-yl-cyclopentyl)-4-trifluoromethyl-benzamide (intermediate AT).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([N:13]1[CH2:18][CH2:17][C:16]3([CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH2:15][CH2:14]1)[CH:7]=[CH:6]2.C=O.[C:26](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([N:13]1[CH2:18][CH2:17][C:16]3([CH2:23][CH2:22][N:21]([CH3:26])[CH2:20][CH2:19]3)[CH2:15][CH2:14]1)[CH:7]=[CH:6]2
Reactant: COc1ccc2cc(N3CCC4(CCNCC4)CC3)ccc2c1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: COc1ccc2cc(N3CCC4(CCN(C)CC4)CC3)ccc2c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 87.6 %

Procedure:
To an ice cooled solution of 3-(6-methoxy-naphthalen-2-yl)-3,9-diaza-spiro[5.5]-undecane (294 mg, 0.95 mmol) in dichloroethane (20 mL), formaldehyde (37% in water, 204 μL, 2.84 mmol) was added and stirred for 1 h at 0° C. Sodium triacetoxyborohydride (402 mg, 1.89 mmol) was added and stirred at room temperature over night. The reaction was quenched with aqueous sodium hydrogencarbonate (sat.) and evaporated. The remaining aqueous phase was extracted three times with dichloromethane and the combined organic phase was dried (sodium sulfate), filtered and evaporated to give 270 mg (80%) of 3-(6-methoxy-naphthalen-2-yl)-9-methyl-3,9-diaza-spiro[5.5]undecane. Mp. 122.2-124.9° C.
Reaction SMILES: F[C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCN(CC)CC>CN(C=O)C>[N+:8]([C:3]1[C:2]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=[CH:5][N:4]=1)([O-:10])=[O:9]
Reactant: Nc1ccccc1
Reactant: O=[N+]([O-])c1ncccc1F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1ncccc1Nc1ccccc1
Temperature: 100 °C
Reaction time: 16 h
Yield: 154.2 %

Procedure:
A mixture of 3-fluoro-2-nitropyridine (1.07 g, 6.75 mmol), aniline (1.8 mL, 20.2 mmol) and Et3N (2.8 mL, 20.2 mmol) in DMF (10 mL) was stirred at 100° C. for 16 h under a nitrogen atmosphere. After cooling to RT, the volatiles were removed under reduced pressure. The resulting residue was partitioned between DCM and water. The aqueous phase was further extracted with DCM (×3) and the combined organic fractions dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% MeOH in DCM) to afford the title compound as a red oil (2.24 g, quantitative). LCMS (Method C): RT 3.03 min [M+H]+ 216.2.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[OH:11].CC(C)=O.[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.O>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[O:11][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCc1ccccc1
Reactant: Cc1cc2cccc(O)c2[nH]1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: Cc1cc2cccc(OCc3ccccc3)c2[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 81 %

Procedure:
To the compound from step A, acetone (15 mL) was added followed by benzyl bromide (670 μL, 5.6 mmol) and Cs2CO3 (1.8 g, 5.6 mmol) and the reaction mixture stirred at RT for 18 h. A second aliquot of BnBr (140 μL) and Cs2CO3 (380 mg) was added and stirring continued for 24 h. The reaction mixture was poured into EtOAc and water, the layers were separated, and the aqueous layer was further extracted with EtOAc (3×50 mL). The combined organic extracts were washed with 1N NaOH and water and dried over MgSO4, filtered, and concentrated in vacuo. Purification by column chromatography (hexanes then 5% EtOAc/hex) afforded 2-methyl-7-benzyloxy indole as an unstable solid (898 mg, 81% yield). 1H NMR impure; 238.17, M+H.
Reaction SMILES: C(N(CC)CC)C.F[C:9]([N:11]([CH3:40])[S:12][N:13]([C:15]([O:17][N:18]=[C:19]([CH3:39])[C:20](=[N:22][O:23][C:24]([N:26]([CH3:38])[S:27][N:28]([C:30]([O:32][N:33]=[C:34]([S:36][CH3:37])[CH3:35])=[O:31])[CH3:29])=[O:25])[CH3:21])=[O:16])[CH3:14])=[O:10].[CH3:41][N:42]([CH3:50])[C:43](=[O:49])[C:44]([S:47][CH3:48])=[N:45][OH:46]>C(Cl)Cl>[CH3:39][C:19](=[N:18][O:17][C:15]([N:13]([CH3:14])[S:12][N:11]([C:9]([O:46][N:45]=[C:44]([S:47][CH3:48])[C:43]([N:42]([CH3:50])[CH3:41])=[O:49])=[O:10])[CH3:40])=[O:16])[C:20]([CH3:21])=[N:22][O:23][C:24]([N:26]([CH3:38])[S:27][N:28]([CH3:29])[C:30]([O:32][N:33]=[C:34]([S:36][CH3:37])[CH3:35])=[O:31])=[O:25]
Reactant: CSC(=NO)C(=O)N(C)C
Reactant: CSC(C)=NOC(=O)N(C)SN(C)C(=O)ON=C(C)C(C)=NOC(=O)N(C)SN(C)C(=O)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CSC(C)=NOC(=O)N(C)SN(C)C(=O)ON=C(C)C(C)=NOC(=O)N(C)SN(C)C(=O)ON=C(SC)C(=O)N(C)C
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 13.1 %

Procedure:
A solution of 1 g of triethylamine in 10 ml of methylene chloride was added dropwise to a solution of 3 g of the crude carbamic fluoride and 1.1 g of methyl 2-(dimethylamino)-N-hydroxy-2-oxoethanimidothioate in 50 ml of methylene chloride at 10° to 20° C. and stirred at room temperature for 2.5 hours. The solution was washed with three 50 ml portions of water, and the organic layer was dried over anhydrous magnesium sulfate. The mixture was filtered, and the filtrate was evaporated. Ether was added to the crude product followed by dilution with methylene chloride until the mass could flow freely. The solid was separated by filtration to give a mixture. The mother liquor was concentrated and diluted with ethers to give 0.5 g of the title compound, m.p. 87°-110° C. (glass).