Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].Cl.[NH2:13][CH2:14][C:15]1([OH:20])[CH2:19][CH2:18][CH2:17][CH2:16]1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([NH:13][CH2:14][C:15]2([OH:20])[CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1
Reactant: NCC1(O)CCCC1
Reactant: O=[N+]([O-])c1cc(Br)ccc1Br
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1cc(Br)ccc1NCC1(O)CCCC1
Yield: 43 %

Procedure:
The mixture of 2,5-dibromonitrobenzene (Tokyo Kasei Kogyo Co., Ltd., 5.4 g, 19.2 mmol), 1-(aminomethyl)cyclopentanol hydrochloride (J. Med. Chem. 1981, 24, 12-16, 4.3 g, 28.4 mmol) and N,N-diisopropylethylamine (8.4 mL, 48.1 mmol) in 1-methyl-2-pyrrolidinone (32 mL) was microwaved for 30 min at 200° C. The reaction was quenched with water and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1 as eluent) to afford the title compound (2.6 g, 43%) as an orange amorphous solid.
Reaction SMILES: [CH2:1]([CH:3]([N:7]1[C:11]2[N:12]=[C:13]([CH3:26])[N:14]=[C:15]([NH:16][C:17]3[C:18]([CH3:25])=[N:19][C:20]([CH3:24])=[CH:21][C:22]=3[CH3:23])[C:10]=2[N:9]=[N:8]1)[CH2:4][CH2:5][CH3:6])[CH3:2].[H-].[Na+].[CH2:29](I)[CH3:30]>CN(C)C=O.O>[CH2:29]([N:16]([C:17]1[C:18]([CH3:25])=[N:19][C:20]([CH3:24])=[CH:21][C:22]=1[CH3:23])[C:15]1[C:10]2[N:9]=[N:8][N:7]([CH:3]([CH2:1][CH3:2])[CH2:4][CH2:5][CH3:6])[C:11]=2[N:12]=[C:13]([CH3:26])[N:14]=1)[CH3:30]
Reactant: CCCC(CC)n1nnc2c(Nc3c(C)cc(C)nc3C)nc(C)nc21
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCC(CC)n1nnc2c(N(CC)c3c(C)cc(C)nc3C)nc(C)nc21
Temperature: 25 °C
Reaction time: 15 h

Procedure:
The product from Example 45, Part B (250 mg, 0.71 mmol) was treated with sodium hydride (26 mg, 0.85 mmol, 80%) and ethyl iodide (0.85 ml, 1.07 mmol) in dry dimethylformamide (7 ml) and stirred at room temperature for 15 h. The reaction was diluted with 150 ml water, and extracted with 3×30 ml ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to dryness. Chromatography on silica gel (20 g, 1/3 hexanes/ethyl acetate) afforded the desired product, 221 mg (81%) as a clear viscous oil.
Reaction SMILES: B(F)(F)F.CCOCC.[CH:10]1([CH2:13][N:14]([CH2:22][C@@H:23]([OH:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:12][CH2:11]1.[N:31]1([C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])[CH2:33][C@@H:32]1[C:34]([O:36][CH3:37])=[O:35]>C(Cl)(Cl)Cl>[CH2:41]([O:40][C:38]([NH:31][C@@H:32]([C:34]([O:36][CH3:37])=[O:35])[CH2:33][O:30][C@@H:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:22][N:14]([C:15]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:21])[CH2:13][CH:10]1[CH2:12][CH2:11]1)=[O:39])[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1
Reactant: CC(C)(C)OC(=O)N(CC1CC1)C[C@@H](O)c1ccccc1
Reactant: COC(=O)[C@H]1CN1C(=O)OCc1ccccc1
Agent: FB(F)F
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: COC(=O)[C@@H](CO[C@H](CN(CC1CC1)C(=O)OC(C)(C)C)c1ccccc1)NC(=O)OCc1ccccc1
Reaction time: 3 h
Yield: 27.4 %

Procedure:
Boron trifluoride diethyl etherate (0.10 mL, 0.84 mmol) was added to a solution of tert-butyl cyclopropylmethyl[(2S)-2-hydroxy-2-phenylethyl]carbamate (2.45 g, 8.39 mmol) and 1-benzyl 2-methyl (2R)-aziridine-1,2-dicarboxylate (1.97 g, 8.39 mmol) in chloroform (20 mL). After 3 h, the reaction was concentrated. Purification by silica gel chromatography (100% hexanes→30% ethyl acetate/hexanes) gave the title compound (1.21 g).
Reaction SMILES: [NH2:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11](CCOS(C)(=O)=O)=[CH:10][CH:9]=2)[C:6](=[O:21])[CH:5]=[CH:4][C:3]=1[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1.N[C:32]1C=C(C=C[CH:40]=1)CCO.[CH:41]1([O:46][C:47](=[O:54])[C@H:48]([CH2:50][CH:51]([CH3:53])[CH3:52])[NH2:49])[CH2:45][CH2:44][CH2:43][CH2:42]1>>[NH2:1][C:2]1[N:7]([C:8]2[CH:13]=[C:12]([CH2:32][CH2:40][NH:49][C@H:48]([C:47]([O:46][CH:41]3[CH2:42][CH2:43][CH2:44][CH2:45]3)=[O:54])[CH2:50][CH:51]([CH3:52])[CH3:53])[CH:11]=[CH:10][CH:9]=2)[C:6](=[O:21])[CH:5]=[CH:4][C:3]=1[C:22]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)=[O:30]
Reactant: CC(C)C[C@H](N)C(=O)OC1CCCC1
Reactant: CS(=O)(=O)OCCc1ccc(-n2c(N)c(C(=O)c3ccc(F)cc3)ccc2=O)cc1
Reactant: Nc1cccc(CCO)c1
Product: CC(C)C[C@H](NCCc1cccc(-n2c(N)c(C(=O)c3ccc(F)cc3)ccc2=O)c1)C(=O)OC1CCCC1

Procedure:
Example 70 was synthesised using similar methodology to Intermediate 4J (instead using 3-aminophenethyl alcohol) and L-Leucine cyclopentyl ester (Intermediate 8).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH2:11][CH2:12]Br)=[C:6]([CH:9]=1)[CH:7]=[O:8].C([O-])([O-])=O.[K+].[K+].[Br:20][C:21]1[CH:22]=[C:23]([OH:27])[CH:24]=[CH:25][CH:26]=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH2:11][CH2:12][O:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([Br:20])[CH:22]=2)=[C:6]([CH:9]=1)[CH:7]=[O:8]
Reactant: Oc1cccc(Br)c1
Reactant: O=Cc1cc(Br)ccc1OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1cc(Br)ccc1OCCOc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
5-Bromo-2-(2-bromoethoxy)benzaldehyde (170 mg, 0.55 mol) obtained in step 1) was dissolved in DMF (20 ml), and K2CO3 (229.43 mg, 1.66 mmol), KI (9.96 mg, 0.06 mmol), and 3-bromophenol (95.46 mg, 0.55 mmol) were added to the solution, followed by stirring for 2 hours at an elevated temperature. After completion of the reaction, the reaction solution was cooled to room temperature, washed with an aqueous saturated NH4Cl solution and extracted with ethyl acetate. The organic layer thus obtained was washed one more time with an aqueous saturated NH4Cl solution. Then, the organic layer was dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/n-hexane=1/9) to afford the object compound (pale yellowish solid, 161 mg, 72.7%).
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1>CC(O)C>[CH2:3]1[CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C@H:1]([OH:11])[CH2:2]1
Reactant: O=C1CCCc2ccccc21
Solvent: CC(C)O
Product: O[C@@H]1CCCc2ccccc21
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 96.9 %

Procedure:
Tetralone (200 ml, 1.5 mol) was charged to the catalyst solution, followed by 2-propanol (0.5 l). The pressure was reduced (28.5 mmHg) and then a sodium 2-propoxide solution (120 ml of 0.1M solution in 2-propanol) was charged. The mixture was stirred at ambient temperature under nitrogen for 4.5 h, at hourly intervals the flask was back filled with nitrogen and sufficient 2-propanol charged to compensate for the volume removed by distillation. This gave (R)-1-tetralol Yield 96.9%, ee 86.9%. The turnover number, integrated over 1 h, was 358 h−1.
Reaction SMILES: [OH:1][C:2]1[C:9]([Br:10])=[CH:8][C:7]([F:11])=[C:6]([Cl:12])[C:3]=1[CH:4]=O.[Br-].Br[CH2:15][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+]>O1CCCC1.CCCCCC>[Cl:12][C:6]1[C:3]2[CH:4]=[CH:15][O:1][C:2]=2[C:9]([Br:10])=[CH:8][C:7]=1[F:11]
Reactant: O=Cc1c(O)c(Br)cc(F)c1Cl
Reactant: BrC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Fc1cc(Br)c2occc2c1Cl
Temperature: 0 °C
Yield: 84.4 %

Procedure:
A suspension of 49.2 gm (0.19 mole) 2-hydroxy-3-bromo-5-fluoro-6-chlorobenzaldehyde and 127 gm (0.29 mole) (bromomethyl)triphenylphosphonium bromide in 230 mL tetrahydrofuran was cooled to 0° C. under a nitrogen atmosphere. To this were added dropwise 330 mL (0.33 mole) potassium tert-butoxide (1M in tetrahydrofuran) over 3 hours. An additional 90 mL (0.09 mole) potassium tert-butoxide (1M in tetrahydrofuran) were then added to react remaining starting material. The reaction mixture was diluted with 700 mL of hexane and the resulting precipitate removed by filtration. The recovered solid was slurried in 300 mL hexane and filtered 4 times. The combined filtrates were washed with 2×500 mL water followed by 500 mL saturated aqueous sodium chloride. The remaining organics were dried over sodium sulfate and concentrated under reduced pressure to provide a residual solid. This solid was slurried and filtered with 4×300 mL diethyl ether to remove triphenylphosphine oxide. The filtrates were concentrated and the residue subjected to silica gel chromatography, eluting with hexane. Fractions containing product were combined and concentrated under reduced pressure to provide 40 gm (83%) of the title compound as a white solid.
Reaction SMILES: [C:1]([N:11]1[CH2:18][C@@H:17]([OH:19])[CH2:16][C@H:12]1[C:13]([OH:15])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH3:20]O.S(=O)(=O)(O)O>C(Cl)(Cl)Cl>[C:1]([N:11]1[CH2:18][C@@H:17]([OH:19])[CH2:16][C@H:12]1[C:13]([O:15][CH3:20])=[O:14])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: O=C(O)[C@@H]1C[C@H](O)CN1C(=O)OCc1ccccc1
Reactant: CO
Agent: O=S(=O)(O)O
Solvent: ClC(Cl)Cl
Product: COC(=O)[C@@H]1C[C@H](O)CN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
6.5 g (0.024 mole) of N-carbobenzyloxy-cis-4-hydroxy-L-proline [J.A.C.S., 79, 189 (1957)] is dissolved in 65 ml. of methanol, stirred, and treated with 0.65 ml. of concentrated sulfuric acid. After stirring at room temperature for one-half hour, the solution is allowed to stand overnight. The bulk of solvent is removed on a rotary evaporator and the oily residue (13 g.) is taken up in 70 ml. of ether and washed with 35 ml. of 10% sodium bicarbonate solution. The wash is back extracted with 35 ml. of ether. The combined organic layers are dried (MgSO4), and the ether is evaporated to give 6.5 g. (96%) of product as a pale yellow viscous oil. [α]D25 -24° (c, 1% in chloroform).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](Cl)=[N:9]2)([O-])=O.[CH:15]1([C:18]2[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=2)[NH2:21])[CH2:17][CH2:16]1.[CH3:25][C:26]1[N:27]=[CH:28][NH:29][C:30]=1[CH:31]=O>>[CH:15]1([C:18]2[CH:19]=[C:20]([NH:21][C:8]3[CH:7]=[CH:6][C:5]4[C:4]([NH:1][CH2:25][C:26]5[NH:27][CH:28]=[N:29][C:30]=5[CH3:31])=[CH:13][CH:12]=[CH:11][C:10]=4[N:9]=3)[CH:22]=[CH:23][CH:24]=2)[CH2:17][CH2:16]1
Reactant: O=[N+]([O-])c1cccc2nc(Cl)ccc12
Reactant: Cc1nc[nH]c1C=O
Reactant: Nc1cccc(C2CC2)c1
Product: Cc1nc[nH]c1CNc1cccc2nc(Nc3cccc(C4CC4)c3)ccc12

Procedure:
The title compound, MS: m/e=370.4 (M+H+), was prepared from 5-nitro-2-chloroquinoline, 3-cyclopropylaniline and 4-methyl-1H-imidazole-5-carbaldehyde as described in example 26.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([CH2:6][C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=2)[NH2:10])=[CH:2]1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:29])[CH2:23][O:24][CH2:25][C:26](O)=[O:27])=[C:17]([C:30]([O:32]C)=[O:31])[CH:16]=1>>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:29])[CH2:23][O:24][CH2:25][C:26]([NH:10][C:9]2[CH:11]=[CH:12][CH:13]=[C:7]([CH2:6][C:3]3[CH:4]=[CH:5][O:1][CH:2]=3)[CH:8]=2)=[O:27])=[C:17]([CH:16]=1)[C:30]([OH:32])=[O:31]
Reactant: Nc1cccc(Cc2ccoc2)c1
Reactant: COC(=O)c1cc(Cl)ccc1NC(=O)COCC(=O)O
Product: O=C(COCC(=O)Nc1ccc(Cl)cc1C(=O)O)Nc1cccc(Cc2ccoc2)c1

Procedure:
Using the same method as in Example 15-(i), 3-(furan-3-ylmethyl)aniline was reacted with the (2-([4-chloro-2-(methoxycarbonyl)phenyl]amino)-2-oxoethoxy)acetic acid obtained in Example 1-(i) to give 5-chloro-2-([(2-([3-(furan-3-ylmethyl)phenyl]amino)-2-oxoethoxy)acetyl]amino)benzoic acid.methyl ester (yield: 34%).
Reaction SMILES: B(F)(F)F.CCOCC.[C:10]([O:17][CH2:18][C:19]1([CH2:23][CH2:24][CH3:25])[CH2:22][O:21][CH2:20]1)(=[O:16])[CH2:11][CH2:12][CH2:13][C:14]#[CH:15].C(N(CC)CC)C>ClCCl>[CH2:11]([C:10]12[O:16][CH2:20][C:19]([CH2:23][CH2:24][CH3:25])([CH2:18][O:17]1)[CH2:22][O:21]2)[CH2:12][CH2:13][C:14]#[CH:15]
Reactant: C#CCCCC(=O)OCC1(CCC)COC1
Agent: FB(F)F
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: ClCCl
Product: C#CCCCC12OCC(CCC)(CO1)CO2
Temperature: 25 °C

Procedure:
Boron trifluoride etherate (0.18 ml) was added to a stirred solution of (3-propyloxetan-3-yl)methyl hex-5-ynoate (1.33 g.) in dry dichloromethane (25 ml) at -70°. The mixture was allowed to warm to room temperature over 16 hours. Triethylamine (0.28 ml) was then added and the solvent was removed in vacuo. The residue was partitioned between diethyl ether and water. The organic phase was separated and further washed with water and brine before drying over anhydrous magnesium sulphate. The solvent was evaporated in vacuo and the residue was purified by column chromatography on alumina eluting with 1:6 dichloromethane:hexane saturated with ammonia. 1-(Pent-4-ynyl)-4-propyl-2,6,7-trioxabicyclo[2.2.2]octane was obtained as a colourless oil which crystallised on trituration (0.64 g) with hexane.
Reaction SMILES: [CH2:1]([C:5]1[CH:36]=[CH:35][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=4)[CH:18]=3)[CH2:12][CH2:11]2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH3:37][O:38][C:39]1[CH:40]=[C:41]([C:49]2[CH:50]=[C:51]([CH:54]=[CH:55][CH:56]=2)[CH2:52][Cl:53])[CH:42]=[C:43]([O:47][CH3:48])[C:44]=1[O:45][CH3:46]>>[ClH:53].[ClH:53].[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([N:9]([CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=4)[CH:18]=3)[CH2:14][CH2:15]2)[CH2:52][C:51]2[CH:54]=[CH:55][CH:56]=[C:49]([C:41]3[CH:42]=[C:43]([O:47][CH3:48])[C:44]([O:45][CH3:46])=[C:39]([O:38][CH3:37])[CH:40]=3)[CH:50]=2)=[CH:35][CH:36]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(NC2CCN(Cc3ccnc(-c4cc(OC)c(OC)c(OC)c4)c3)CC2)cc1
Reactant: COc1cc(-c2cccc(CCl)c2)cc(OC)c1OC
Product: CCCCc1ccc(N(Cc2cccc(-c3cc(OC)c(OC)c(OC)c3)c2)C2CCN(Cc3ccnc(-c4cc(OC)c(OC)c(OC)c4)c3)CC2)cc1
Product: Cl

Procedure:
4-(4-Butylanilino)-1-[[2-(3,4,5-trimethoxyphenyl)pyridin-4-yl]methyl]piperidine (147 mg) and 3-(3,4,5-trimethoxyphenyl)benzyl chloride (114 mg) were condensed in the same manner as described in Example 9. The title compound was obtained as yellow powder after converting a free base to a dihydrochloride.
Reaction SMILES: [CH3:1][CH:2]([CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:26](OCC)(=O)CCC/C=C\C/C=C\C/C=C\C/C=C\CCCCC>>[CH3:1][C:2]([CH3:26])([CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCC(C)C(=O)OCC
Reactant: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)OCC
Product: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCC(C)(C)C(=O)OCC

Procedure:
The ethyl 2-methylarachidonate produced in Example 1 is substituted for the ethyl arachidonate in Example 1 and the procedure of Example 1 is repeated to afford ethyl 2,2-dimethylarachidonate. That compound is represented structurally by the following formula ##SPC3##
Reaction SMILES: [CH3:1][C@H:2]1[CH2:4][O:3]1.C(N(CC)CC)C.[C:12]1([OH:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CN=C1.C([Si](C(C)C)(C(C)C)Cl)(C)C>CN(C=O)C>[O:18]([CH2:1][C@@H:2]([OH:3])[CH3:4])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Oc1ccccc1
Reactant: C[C@H]1CO1
Agent: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C[C@H](O)COc1ccccc1
Temperature: 150 °C
Yield: 108.6 %

Procedure:
A microwave vessel was charged with (S)-2-methyl-oxirane (0.46 ml, 7.78 mmol), triethylamine (0.33 ml, 2.36 mmol), phenol (222 mg, 2.36 mmol) and DMF (2.0 ml). The mixture was heated by microwave for 20 minutes at 150° C. The reaction was concentrated and dried under reduced pressure. The crude mixture (approximately 9:1) was dissolved in DMF (3.0 ml) and treated with imidazole (160 mg, 2.36 mmol) and Triisopropylchlorosilane (181 mg, 0.94 mmol) overnight at room temperature under nitrogen. The reaction was concentrated under reduced pressure and the crude product was purified via flash chromatography using 3:2/heptane:Ethyl acetate as eluant. Fractions containing product were combined and concentrated to afford (S)-1-Phenoxy-propan-2-ol (390 mg, 62%) as a clear oil.
Reaction SMILES: S(C)C.C1(C)C=CC=CC=1.[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH3:33])=[C:16]([CH:32]=1)[C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]1)=[O:18]>C1COCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH3:33])=[C:16]([C@H:17]([OH:18])[C@@H:19]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:20]2)[CH:32]=1
Reactant: Cc1ccc(Cl)cc1C(=O)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Solvent: Cc1ccccc1
Solvent: CSC
Solvent: C1CCOC1
Product: Cc1ccc(Cl)cc1[C@H](O)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Temperature: -15 °C
Reaction time: 2 h

Procedure:
A mixture of 10 M BH3.Me2S in THF (25.4 mL, 0.254 mol) and 1M R-CBS-oxazaborolidine in toluene (38 mL, 0.038 mol) were dissolved in 100 mL anhydrous THF and cooled to −15° C. (R)-tert-butyl 3-(5-chloro-2-methylbenzoyl)piperidine-1-carboxylate in 200 mL anhydrous THF was added dropwise to the above solution and stirred at −15° C. for 2 hr. The reaction was quenched with methanol (300 mL). The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give (R)-tert-butyl 3-((R)-(5-chloro-2-methylphenyl)(hydroxy)methyl)piperidine-1-carboxylate (32 g), which contained 30% isomer.
Reaction SMILES: ClC1N=C(N)C=NC=1.CN1CCNCC1.Cl[C:17]1[N:35]=[C:20]2[C:21]([C:25]3[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=3)=[CH:22][CH:23]=[CH:24][N:19]2[N:18]=1.[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([C:43]2[CH:48]=[N:47][CH:46]=[C:45]([NH2:49])[N:44]=2)[CH2:39][CH2:38]1>CN(C)C=O.O>[CH3:36][N:37]1[CH2:38][CH2:39][N:40]([C:43]2[CH:48]=[N:47][CH:46]=[C:45]([NH2:49])[N:44]=2)[CH2:41][CH2:42]1.[CH3:34][S:31]([C:28]1[CH:29]=[CH:30][C:25]([C:21]2[C:20]3[N:19]([N:18]=[C:17]([NH:49][C:45]4[N:44]=[C:43]([N:40]5[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]5)[CH:48]=[N:47][CH:46]=4)[N:35]=3)[CH:24]=[CH:23][CH:22]=2)=[CH:26][CH:27]=1)(=[O:33])=[O:32]
Reactant: CS(=O)(=O)c1ccc(-c2cccn3nc(Cl)nc23)cc1
Agent: CN1CCN(c2cncc(N)n2)CC1
Agent: CN1CCNCC1
Agent: Nc1cncc(Cl)n1
Solvent: O
Solvent: CN(C)C=O
Product: CN1CCN(c2cncc(Nc3nc4c(-c5ccc(S(C)(=O)=O)cc5)cccn4n3)n2)CC1
Temperature: 100 °C

Procedure:
4-Methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-6′-ylamine was prepared from 6-chloro-pyrazin-2-ylamine (1.00 g, 7.72 mmol) and 1-methylpiperazine (942 L, 8.49 mmol) combined in N,N-dimethylformamide (35 mL) and heated at 100° C. overnight. The reaction was poured into water and extracted with 3 portions of dichloromethane. The combined organic was dried over magnesium sulfate, filtered and evaporated to yield an off-white solid. This solid was purified via chromatography (silica gel 40 g methanol in dichloromethane). Product isolated as a tan oil that solidified upon standing. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 7.33 (s, 1H), 7.16 (s, 1H), 5.93 (s, 2H), 3.40 (s, 4H), 2.36 (s, 4H), 2.20 (s, 3H). 386b) [8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-6′-yl)-amine was prepared from 2-chloro-8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (133 mg, 0.434 mmol) and 4-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-6′-ylamine (92.159 mg, 0.47689 mmol) in a manner analogous to Example 2d. Product isolated as an off-white foam (28.64 mg, 14.2%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.07 (s, 1H), 8.91 (d, J=6.6 Hz, 1H), 8.59 (s, 1H), 8.41 (d, J=8.5 Hz, 2H), 8.08 (d, J=8.3 Hz, 2H), 8.00 (d, J=7.6 Hz, 1H), 7.83 (s, 1H), 7.23 (t, J=14.5, 7.4 Hz, 1H), 3.32 (s, 3H), 3.56 (s, 4H), 2.40 (s, 4H), 2.23 (s, 3H). MS=465 (MH)+.
Reaction SMILES: C(OC(=O)NC(C)(C)C/C=C/[C:12](=O)[N:13]([C@@H:15]([C:25](=[O:40])[N:26]([CH3:39])[C@@H:27]([C:35](=[O:38])[NH:36][CH3:37])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)C)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH2:18]([O:17][CH2:16][C@@H:15]([NH:13][CH3:12])[C:25]([N:26]([CH3:39])[C@@H:27]([C:35](=[O:38])[NH:36][CH3:37])[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:40])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](COCc1ccccc1)N(C)C(=O)/C=C/CC(C)(C)NC(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](COCc1ccccc1)NC
Temperature: 25 °C
Reaction time: 0.12 h
Yield: 75 %

Procedure:
((3E)-4-(N-((1R)-2-Benzyloxy-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid tert-butyl ester (0.275 g; 0.452 mmol) was dissolved in methylene chloride (3 mL) and trifluoroacetic acid (3 mL) was added and the reaction mixture was stirred for 7 min at room temperature. Methylene chloride (30 mL), an aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 30 mL) and sodium hydrogen carbonate (solid) were added to the reaction mixture until pH 8. The organic phase was dried (magnesium sulfate) and evaporated in vacuo to afford 0.13 g of the title compound.
Reaction SMILES: CC(O[CH2:5][C:6]1[CH2:15][S:14][C@@H:9]2[C@H:10]([NH2:13])[C:11](=[O:12])[N:8]2[C:7]=1[C:16]([OH:18])=[O:17])=O.[SH:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]2[N:27]=[CH:28][C:29]([C:30]([OH:32])=[O:31])=[C:22]2[N:21]=1.B(F)(F)F.O>C(#N)C>[NH2:13][C@@H:10]1[C:11](=[O:12])[N:8]2[C@@H:9]1[S:14][CH2:15][C:6]([CH2:5][S:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]3[N:27]=[CH:28][C:29]([C:30]([OH:32])=[O:31])=[C:22]3[N:21]=1)=[C:7]2[C:16]([OH:18])=[O:17]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: Cc1cc(S)nc2c(C(=O)O)cnn12
Agent: FB(F)F
Solvent: O
Solvent: CC#N
Product: Cc1cc(SCC2=C(C(=O)O)N3C(=O)[C@@H](N)[C@H]3SC2)nc2c(C(=O)O)cnn12
Reaction time: 1.5 h

Procedure:
A suspension of 4.00 g of (7R)-7-aminocephalosporanic acid and 3.34 g of 5-mercapto-7-methylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid in 20 ml of acetonitrile was treated with 25 ml of a 20 percent solution of boron trifluoride in acetonitrile and the mixture was stirred at 20° for 1.5 hours. 150 ml of cold water were added and the mixture was stirred at 0° for 1.5 hours. The precipitate was filtered off under suction and dried. There was obtained (6R,7R)-7-amino-3-[[(3-carboxy-7-methylpyrazolo[1,5-a]pyri-midine-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid as an almost colorless powder.