Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:11]1[CH2:18][CH2:17][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].[C:19](Cl)(=O)C>CO>[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([O:15][CH3:19])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: O=C(O)[C@@H]1CCCN1C(=O)OCc1ccccc1
Reactant: CC(=O)Cl
Solvent: CO
Product: COC(=O)[C@@H]1CCCN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A 12.5 g (47.4 mmol) sample of CBZ-L-proline (Aldrich) was dissolved in 250 mL of methanol and 1.7 mL of acetyl chloride was added. The reaction mixture was stirred at room temperature for 16 hours. The solvents were removed, the residue was dissolved in CHCl3, and this solution was washed with NaHCO3 solution, dried, filtered and concentrated. The residue was purified on a silica gel column, eluting with 1:1 ethyl acetate:hexane to give 14 g of the title compound.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:9]([NH:10][C:11](=[O:21])[CH2:12][S:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)=[CH:8][N:7]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:6]=1)=[O:4].[OH-].[Na+].Cl>CO>[Br:20][C:17]1[CH:18]=[CH:19][C:14]([S:13][CH2:12][C:11]([NH:10][C:9]2[C:5]([C:3]([OH:4])=[O:2])=[N:6][N:7]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:8]=2)=[O:21])=[CH:15][CH:16]=1
Reactant: COC(=O)c1nn(CCc2ccccc2)cc1NC(=O)CSc1ccc(Br)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(CSc1ccc(Br)cc1)Nc1cn(CCc2ccccc2)nc1C(=O)O
Reaction time: 1 h
Yield: 92.7 %

Procedure:
100 mg (0.2 mM) of the compound obtained in Example 1 was dissolved in 1 ml of methanol to which 0.3 ml (0.3 mM, 1.5 eq) of 1N sodium hydroxide was added dropwise, and the resulting mixture was heated with stirring under a nitrogen atmosphere for 1 hour. The resultant was acidified with 1N hydrochloric acid solution, and extracted with ethyl acetate and brine. The organic solvent layer was dried over anhydrous sodium sulfate, filtered, and then distilled under reduced pressure, to obtain 90 mg (91.5%) of the title compound.
Reaction SMILES: Cl[C:2]1[N:20]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([P:16]([CH3:19])([CH3:18])=[O:17])=[CH:12][CH:11]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][C:29]2=[O:35])[CH:25]=[CH:26][CH:27]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:18][P:16]([CH3:19])([C:13]1[CH:14]=[CH:15][C:10]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:21][C:22]4[CH:23]=[C:24]([N:28]5[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][C:29]5=[O:35])[CH:25]=[CH:26][CH:27]=4)[N:20]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:11][CH:12]=1)=[O:17]
Reactant: CN1CCN(c2cccc(N)c2)C(=O)C1
Reactant: CP(C)(=O)c1ccc(-c2cccn3nc(Cl)nc23)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCN(c2cccc(Nc3nc4c(-c5ccc(P(C)(C)=O)cc5)cccn4n3)c2)C(=O)C1

Procedure:
1-(3-{8-[4-(Dimethyl-phosphinoyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino}-phenyl)-4-methyl-piperazin-2-one was prepared from 2-chloro-8-[4-(dimethyl-phosphinoyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridine (100.0 mg, 0.3271 mmol) and 1-(3-amino-phenyl)-4-methyl-piperazin-2-one (75.0 mg, 0.365 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (28.0 mg, 0.0512 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a pale yellow solid (0.076 g, 49%). MP=208-211° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.48 (d, J=6.8 Hz, 1H), 8.14 (d, J=7.8 Hz, 2H), 7.92-7.85 (m, 2H), 7.69 (s, 1H), 7.64 (d, J=7.3 Hz, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.37 (t, J=7.9 Hz, 1H), 7.01 (t, J=7.1 Hz, 1H), 6.97-6.90 (m, 2H), 3.80-3.75 (m, 2H), 3.32 (s, 2H), 2.85-2.80 (m, 2H), 2.43 (s, 3H), 1.80 (s, 3H), 1.77 (s, 3H). MS=475 (MH)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH3:13])([CH3:12])[CH2:7][CH2:6][CH2:5]2.[Br:14]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:14][CH:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=2)[C:8]([CH3:13])([CH3:12])[CH2:7][CH2:6]1
Reactant: CC1(C)CCCc2cc(Br)ccc21
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CC1(C)CCC(Br)c2cc(Br)ccc21

Procedure:
To a solution of 1.2 g (5.0 mmol) of 6-bromo-1,2,3,4-tetrahydro-1,1-dimethylnaphthalene (Compound F) in 20 ml of CCl4 was added 0.97 g (5.5 mmol) of N-bromosuccinimide followed by 20 mg (0.08 mmol ) of benzoylperoxide. The mixture was refluxed for 3 hours, filtered and the filtrate washed with water (5 ml). The organic phase was dried over MgSO4 and then concentrated in vacuo to yield the title compound as a pale yellow oil.
Reaction SMILES: [CH2:1]([N:8]1[C:13](=[O:14])[CH2:12][O:11][CH2:10][CH:9]1[C:15]([OH:17])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([C@H:26]([NH2:28])[CH3:27])[CH:23]=[CH:24][CH:25]=1>>[CH2:1]([N:8]1[C:13](=[O:14])[CH2:12][O:11][CH2:10][CH:9]1[C:15]([NH:28][C@@H:26]([C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH3:18])[CH:21]=1)[CH3:27])=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C1COCC(=O)N1Cc1ccccc1
Reactant: COc1cccc([C@@H](C)N)c1
Product: COc1cccc([C@@H](C)NC(=O)C2COCC(=O)N2Cc2ccccc2)c1

Procedure:
The title compound was prepared by following the similar procedure as described in Intermediate-7 by using 4-benzyl-5-oxomorpholine-3-carboxylic acid (Organic and Bio-Organic Chemistry (1972-1999); (1985); 2577-2580) and (R)-1-(3-methoxyphenyl) ethanamine. m/z 369.2.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH2:17][C:16](=[O:18])[NH:15][C:14]3[CH:19]=[C:20]([Cl:26])[C:21]([N:23]([CH3:25])[CH3:24])=[CH:22][C:13]=3[N:12]=2)[CH:8]=[CH:9][CH:10]=1)=O.[CH2:27]([NH:29][C:30]([NH2:32])=[S:31])[CH3:28]>C1COCC1.CCOC(C)=O>[Cl:26][C:20]1[C:21]([N:23]([CH3:25])[CH3:24])=[CH:22][C:13]2[N:12]=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([C:3]4[N:32]=[C:30]([NH:29][CH2:27][CH3:28])[S:31][CH:2]=4)[CH:6]=3)[CH2:17][C:16](=[O:18])[NH:15][C:14]=2[CH:19]=1
Reactant: CN(C)c1cc2c(cc1Cl)NC(=O)CC(c1cccc(C(=O)CBr)c1)=N2
Reactant: CCNC(N)=S
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCNc1nc(-c2cccc(C3=Nc4cc(N(C)C)c(Cl)cc4NC(=O)C3)c2)cs1
Temperature: 60 °C
Yield: 18.3 %

Procedure:
A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one (130 mg) (Example 193a) and N-ethyl-thiourea (31 mg) in THF (3 mL) was heated at 60° C. for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCO3 solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/hexane (1:1) as eluent. The purified product was triturated with Et2O to give the title compound (24 mg) as yellow solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:11][C:10](=[S:12])[NH:9][C:8]=2[CH:13]=1)([O-:3])=[O:2].C(N(CC)CC)C.Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1>C(Cl)(Cl)Cl.C(OCC)(=O)C>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][S:12][C:10]2[O:11][C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:13][C:8]=3[N:9]=2)=[CH:24][CH:25]=1
Reactant: Clc1ccc(CBr)cc1
Reactant: O=[N+]([O-])c1ccc2oc(=S)[nH]c2c1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc2oc(SCc3ccc(Cl)cc3)nc2c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 77.9 %

Procedure:
To a suspension of 5-nitrobenzo[d]oxazole-2(3H)-thione (196.2 mg, 1.0 mmol) in chloroform (10 mL) was added triethylamine (278 μL, 2 mmol) followed by 1-(bromomethyl)-4-chlorobenzene (226 mg, 1.1 mmol). The reaction was stirred at 60° C. for 2 h. After cooling, the reaction was diluted with ethyl acetate, washed with dilute aqueous hydrochloric solution and brine. The combined organic layers were dried over anhydrous MgSO4 and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes 1:10 v/v to afford 250 mg (78%) of the title compound (LCMS RT=7.64 min)
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:21])[NH:6][C:7]2[C:12]([CH:13]=1)=[C:11]([O:14]CC=C(C)C)[CH:10]=[CH:9][C:8]=2[CH3:20])([CH3:3])[CH3:2]>CN(C)C1C=CC=CC=1>[CH3:13][CH:4]([C:10]1[C:11]([OH:14])=[C:12]2[C:7](=[C:8]([CH3:20])[CH:9]=1)[NH:6][C:5](=[O:21])[C:4]([CH:1]([CH3:2])[CH3:3])=[CH:13]2)[C:1]([CH3:3])=[CH2:2]
Reactant: CC(C)=CCOc1ccc(C)c2[nH]c(=O)c(C(C)C)cc12
Solvent: CN(C)c1ccccc1
Product: C=C(C)C(C)c1cc(C)c2[nH]c(=O)c(C(C)C)cc2c1O
Temperature: 202 °C
Reaction time: 2 h
Yield: 178.6 %

Procedure:
3-Isopropyl-8-methyl-5-prenyloxycarbostyril (1.90 g, 6.67 mmol) was suspended in N,N-dimethylaniline (30 ml). The suspension was heated and dissolved while stirring at 202° C. for 2 hours. The reaction system was heated under reduced pressure until condensed. The resultant residue was recrystallized from chloroform-hexane to obtain 1.70 g of the title compound as pale yellow powdery crystals (89.5%).
Reaction SMILES: [OH:1][CH:2]([C:5]1[N:6]=[C:7]([CH3:10])[S:8][CH:9]=1)[CH2:3][NH2:4].[C:11]([CH:15]=[C:16]([C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](=O)[CH3:26])=[CH:20][CH:19]=1)[CH3:17])([O:13][CH3:14])=[O:12]>>[C:11]([CH:15]=[C:16]([C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH:25]([NH:4][CH2:3][CH:2]([OH:1])[C:5]2[N:6]=[C:7]([CH3:10])[S:8][CH:9]=2)[CH3:26])=[CH:20][CH:19]=1)[CH3:17])([O:13][CH3:14])=[O:12]
Reactant: COC(=O)C=C(C)c1ccc(CC(C)=O)cc1
Reactant: Cc1nc(C(O)CN)cs1
Product: COC(=O)C=C(C)c1ccc(CC(C)NCC(O)c2csc(C)n2)cc1

Procedure:
Prepared analogously to Example 13 by reaction of 2-hydroxy-2-(2-methyl-thiazol-4-yl)ethanamine with 1-[4-(2-carbomethoxy-1-methylethenyl)phenyl]propan-2-one followed by purification of the base on a silica gel column using toluene/methanol=19:1 as eluant.
Reaction SMILES: [CH:1]1([C:7](=[O:11])[CH:8]=[N+:9]=[N-:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:12]([O:14][P:15]([C:20]([P:22](=[O:29])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])=[CH2:21])(=[O:19])[O:16][CH2:17][CH3:18])[CH3:13]>CCOCC>[CH2:24]([O:23][P:22]([C:20]1([P:15](=[O:19])([O:14][CH2:12][CH3:13])[O:16][CH2:17][CH3:18])[CH2:21][C:8]([C:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:11])=[N:9][NH:10]1)(=[O:29])[O:26][CH2:27][CH3:28])[CH3:25]
Reactant: [N-]=[N+]=CC(=O)C1CCCCC1
Reactant: C=C(P(=O)(OCC)OCC)P(=O)(OCC)OCC
Solvent: CCOCC
Product: CCOP(=O)(OCC)C1(P(=O)(OCC)OCC)CC(C(=O)C2CCCCC2)=NN1

Procedure:
1-Cyclohexyl-2-diazoethanone (I, PREPARATION 2, 3.1 g) and ethenylidene bisphosphonic acid tetraethyl ester (II, PREPARATION 1, 6.00 g) are stirred in ether (20 ml) for 24 hrs at 22°. The precipitate is filtered, washed with ether, then recrystallized from ethyl acetate to give the title compound, mp 166°-165°; MS (m/e) 452, 341, 315, 287, 259, 241, 223 and 205; IR (mineral oil mull) 3186, 1656, 1552, 1449, 1267, 1253, 1241, 1162, 1041, 1019, 995 and 969 cm-1 ; NMR (CDCl3) 6.77, 4.24, 3.45, 3.24 and 1.9-1.2 δ.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][C:20]=1Cl)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-])=O)[CH:10]=1)=[O:8])([O-])=O.[O-2].[Ca+2].[H][H]>[Pd].ClCCCl>[NH2:1][C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=1)=[O:8]
Reactant: [H][H]
Reactant: O=C(c1cccc([N+](=O)[O-])c1)c1ccc(Cl)c([N+](=O)[O-])c1
Agent: [Pd]
Agent: [Ca+2]
Agent: [O-2]
Solvent: ClCCCl
Product: Nc1cccc(C(=O)c2cccc(N)c2)c1
Temperature: 70 °C

Procedure:
In an autoclave, there are charged 46 g (0.15 moles) of 3,3'-dinitro-4-chloro benzophenone, 11.2 g (0.2 moles) of calcium oxide, 1 g of 5% palladium/alumina catalyst (available from Nihon-Engelhardt Co.) and 250 ml of 1,2-dichloro ethane. With the mixture being stirred at a temperature of 30°-35° C., the reaction proceeds by the introduction of hydrogen for seven hours under a constant pressure of 10 Kg/cm2.G. After completion of the reaction, the reaction mixture is heated up to 70° C. for hot-filtering so as to remove the catalyst and the inorganic salt. On cooling, there is obtained 3,3'-diamino benzophenone as yellow needle-like crystals. The crystals are filtered, washed with 20 ml of 1,2-dichloro ethane and dried. Yield 24.8 g (78%). M.P. 149°-150° C. Recrystallization from ethanol gives yellow needle-like pure crystals of the benzophenone. M.P. 150°-151° C.
Reaction SMILES: S(=O)(=O)(O)O.[F:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[O:13][CH2:12][CH2:11][C:10]2=[O:17].[N+:18]([O-])([OH:20])=[O:19]>O>[F:6][C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([N+:18]([O-:20])=[O:19])[CH:16]=1)[O:13][CH2:12][CH2:11][C:10]2=[O:17]
Reactant: O=C1CCOc2ccc(F)cc21
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C1CCOc2c1cc(F)cc2[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Concentrated sulfuric acid (5 mL) was cooled to −15° C., treated with 6-fluoro-2,3-dihydro-4H-chromen-4-one (1.0 g, 6.0 mmol), treated with a mixture of 70% nitric acid (1.8 mL) and concentrated sulfuric acid (2.8 mL), stirred at 0° C. for 2 hours and poured into water. The resulting solid was collected by filtration, washed with water and dried under vacuum. Purification of the residue on silica gel eluting with 1:1 ethyl acetate:hexanes provided the title compound.
Reaction SMILES: [NH2:1][N:2]1[C:6]([C:7]#[N:8])=[CH:5][CH:4]=[C:3]1[CH:9]1[CH2:12][N:11]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:10]1.C(O)(=O)C.[CH:27](N)=[NH:28]>C(O)CCC>[NH2:8][C:7]1[C:6]2=[CH:5][CH:4]=[C:3]([CH:9]3[CH2:10][N:11]([C:13]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[O:14])[CH2:12]3)[N:2]2[N:1]=[CH:27][N:28]=1
Reactant: N#Cc1ccc(C2CN(C(=O)OCc3ccccc3)C2)n1N
Reactant: N=CN
Solvent: CCCCO
Solvent: CC(=O)O
Product: Nc1ncnn2c(C3CN(C(=O)OCc4ccccc4)C3)ccc12
Temperature: 25 °C
Yield: 39.8 %

Procedure:
A solution of benzyl 3-(1-amino-5-cyano-1H-pyrrol-2-yl)azetidine-1-carboxylate (575 mg, 1.94 mmoL) and formamidine acetate (2.02 g, 19.4 mmol) in 1-butanol (8 mL) was stirred at 120° C. for 4 hours. The mixture was then cooled to rt and was partitioned between EtOAc (25 mL) and H2O (25 mL). The layers were separated and the aqueous layer was further extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The crude material was purified by ISCO® chromatography using 3:1 ethyl acetate/hexanes to obtain 250 mg (40%) of the desired product. ES-MS m/z 324.34 [M+H]+, HPLC RT (min) 2.30.
Reaction SMILES: CCCCC/C=C/C[CH2:9][C:10]([NH:12][CH:13]1[CH:18]([O:19][C:20]2[C:25]3[O:26][C:27]4[CH:32]=[CH:31][C:30]([CH:33]([O:116][CH:117]5[O:122][CH:121]([CH2:123][OH:124])[CH:120]([OH:125])[CH:119]([OH:126])[CH:118]5[NH:127][C:128]([CH3:130])=[O:129])[CH:34]5[NH:54][C:52](=[O:53])[CH:51]([NH:55][C:56]([CH:58]6[NH:59][C:60]([CH:62]7[NH:95][C:93](=[O:94])[CH:82]([CH:83](O)[C:84]8[CH:90]=[CH:89][C:87]([O:88][C:21]=2[CH:22]=[C:23]6[CH:24]=3)=[C:86]([Cl:91])[CH:85]=8)[NH:81][C:79](=[O:80])[CH:78]([NH2:96])[C:76]2=[CH:77][C:72](=[C:73]([OH:97])[CH:74]=[CH:75]2)[O:71][C:65]2=[C:66](C)[C:67]([OH:69])=[CH:68][C:63]7=[CH:64]2)=[O:61])=[O:57])[C:49]2=[CH:50][C:45](=[C:46]([OH:98])[CH:47]=[CH:48]2)[C:44]2[C:39](=[CH:40][C:41]([OH:111])=[CH:42][C:43]=2[O:99][CH:100]2[O:105][CH:104]([CH2:106][OH:107])[CH:103]([OH:108])[CH:102]([OH:109])[CH:101]2[OH:110])[CH:38]([C:112]([O:114]C)=[O:113])[NH:37][C:35]5=[O:36])=[CH:29][C:28]=4[Cl:131])[O:17][CH:16]([CH2:132][OH:133])[CH:15]([OH:134])[CH:14]1[OH:135])=[O:11]>Cl>[CH3:9][C:10]([NH:12][C@@H:13]1[C@H:18]([O:19][C:20]2[C:25]3[O:26][C:27]4[CH:32]=[CH:31][C:30]([C@@H:33]([O:116][C@@H:117]5[O:122][C@@H:121]([CH2:123][OH:124])[C@@H:120]([OH:125])[C@H:119]([OH:126])[C@@H:118]5[NH:127][C:128]([CH3:130])=[O:129])[C@@H:34]5[NH:54][C:52](=[O:53])[C@H:51]([NH:55][C:56]([C@@H:58]6[NH:59][C:60]([C@H:62]7[NH:95][C:93](=[O:94])[C@@H:82]([CH2:83][C:84]8[CH:90]=[CH:89][C:87]([O:88][C:21]=2[CH:22]=[C:23]6[CH:24]=3)=[C:86]([Cl:91])[CH:85]=8)[NH:81][C:79](=[O:80])[C@H:78]([NH2:96])[C:76]2[CH:75]=[CH:74][C:73]([OH:97])=[C:72]([CH:77]=2)[O:71][C:65]2=[CH:64][C:63]7=[CH:68][C:67]([OH:69])=[CH:66]2)=[O:61])=[O:57])[C:49]2[CH:48]=[CH:47][C:46]([OH:98])=[C:45]([CH:50]=2)[C:44]2[C:43]([O:99][C@H:100]3[O:105][C@H:104]([CH2:106][OH:107])[C@@H:103]([OH:108])[C@@H:102]([OH:109])[C@@H:101]3[OH:110])=[CH:42][C:41]([OH:111])=[CH:40][C:39]=2[C@@H:38]([C:112]([OH:114])=[O:113])[NH:37][C:35]5=[O:36])=[CH:29][C:28]=4[Cl:131])[O:17][C@@H:16]([CH2:132][OH:133])[C@@H:15]([OH:134])[C@@H:14]1[OH:135])=[O:11]
Reactant: CCCCC/C=C/CCC(=O)NC1C(Oc2c3cc4cc2Oc2ccc(cc2Cl)C(OC2OC(CO)C(O)C(O)C2NC(C)=O)C2NC(=O)C(NC(=O)C4NC(=O)C4NC(=O)C(NC(=O)C(N)c5ccc(O)c(c5)Oc5cc4cc(O)c5C)C(O)c4ccc(c(Cl)c4)O3)c3ccc(O)c(c3)-c3c(OC4OC(CO)C(O)C(O)C4O)cc(O)cc3C(C(=O)OC)NC2=O)OC(CO)C(O)C1O
Agent: Cl
Product: CC(=O)N[C@@H]1[C@H](Oc2c3cc4cc2Oc2ccc(cc2Cl)[C@@H](O[C@@H]2O[C@@H](CO)[C@@H](O)[C@H](O)[C@@H]2NC(C)=O)[C@@H]2NC(=O)[C@H](NC(=O)[C@@H]4NC(=O)[C@H]4NC(=O)[C@@H](Cc5ccc(c(Cl)c5)O3)NC(=O)[C@H](N)c3ccc(O)c(c3)Oc3cc(O)cc4c3)c3ccc(O)c(c3)-c3c(O[C@H]4O[C@H](CO)[C@@H](O)[C@@H](O)[C@@H]4O)cc(O)cc3[C@@H](C(=O)O)NC2=O)O[C@@H](CO)[C@@H](O)[C@@H]1O
Temperature: 2.5 °C

Procedure:
Teicoplanin A2 (10 g) is added to 1N hydrochloric acid (150 ml) preheated to 80° C. while stirring. After about 45 minutes the reaction mixture is cooled to 0-5° C. and 37% hydrochloric acid (30 ml) is added. Stirring is maintained for about 10 minutes, after which the precipitated solid is recovered by filtration, washed with 20 ml of 2N HCl, then with ethyl ether, and dried overnight over potassium hydroxide pellets at room temperature, resulting in the crude product of the title (8.3 g).
Reaction SMILES: Cl[C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1.[CH:10]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([OH:22])[CH2:18][CH2:17]1)=[O:15])([CH3:12])[CH3:11].CC(C)([O-])C.[K+].N1C=CC=NC=1>O1CCCC1>[CH:10]([O:13][C:14]([N:16]1[CH2:17][CH2:18][CH:19]([O:22][C:2]2[C:7]([CH3:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=2)[CH2:20][CH2:21]1)=[O:15])([CH3:12])[CH3:11]
Reactant: CC(C)OC(=O)N1CCC(O)CC1
Reactant: Cc1c(Cl)ncnc1Cl
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: c1cncnc1
Product: Cc1c(Cl)ncnc1OC1CCN(C(=O)OC(C)C)CC1
Temperature: -12.5 °C
Yield: 96.3 %

Procedure:
4,6-Dichloro-5-methylpyrimidine (1) (2.4235 Kg, 1.000 equivalents) and 4-hydroxypiperidine-1-carboxylic acid isopropyl ester (2) (2.8182 Kg, 1.012 equivalents) were dissolved in tetrahydrofuran (THF, 25.0028 Kg), and the resulting solution was cooled to −15 to −10° C. To the cold solution, potassium-tert-butoxide in tetrahydrofuran (1 M, 12.6051 Kg, 0.9399 equivalents) was added at a rate sufficiently slow to maintain the reaction mixture below 0° C. with reactor jacket cooling. The reaction mixture was then stirred at about −5° C. for about 2 hours before an additional portion of potassium-tert-butoxide in tetrahydrofuran (1 M, 0.5692 Kg, 0.0424 equivalents) was added to achieve >97% conversion of the pyrimidine after an additional hour of stirring at about −5° C. Most of the solvent was then removed by distillation at 30-65° C., ≦80 torr. Addition of water (19.9681 Kg) to the evaporation residue precipitated the product. Distillative removal of THF was then completed at 30-65° C., ≦80 torr, and the resulting stirred slurry was cooled to 0° C. for an hour. The solids were then collected by suction filtration, washed with water (8.011 Kg, 4° C.), and vacuum dried to constant weight at 50° C., ≦40 torr to provide product (3) (4.491 Kg, 96.3% yield).
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[C:13]1([P:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1C=CC=CC=1>[C:26]1([P:19](=[CH:2][C:3]([O:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[O:4])([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: O=C(CBr)OCc1ccccc1
Solvent: c1ccccc1
Product: O=C(C=P(c1ccccc1)(c1ccccc1)c1ccccc1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 41 %

Procedure:
A 22.9 g quantity of benzyl bromoacetate was dissolved in 100 ml of dry benzene. A 26.2 g quantity of triphenylphosphine was added thereto at room temperature and stirred overnight. The precipitated solids were collected by filtration, washed with benzene and dissolved in 250 ml of dichloromethane. A 14 ml quantity of triethylamine was added with ice-cooling and stirred with ice-cooling for 30 minutes and at room temperature for a further 30 minutes. The reaction mixture was transferred to a separating funnel, washed with water and dried over magnesium sulfate. The solvent was distilled off and diethyl ether was added to the residue. The resulting precipitate was collected by filtration to provide the title compound as white crystals (yield 41%).
Reaction SMILES: [CH2:1]([N:3]([CH2:26][CH3:27])[CH2:4][CH2:5][NH:6][C:7](=[O:25])[C:8]1[CH:13]=[CH:12][C:11]([N:14](S(C)(=O)=O)[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:10][C:9]=1[O:23][CH3:24])[CH3:2].[OH-].[K+].C(=O)(O)[O-].[Na+].C(Cl)Cl>O1CCCC1>[CH2:26]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][NH:6][C:7](=[O:25])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][S:15]([CH3:18])(=[O:16])=[O:17])=[CH:10][C:9]=1[O:23][CH3:24])[CH3:27]
Reactant: CCN(CC)CCNC(=O)c1ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc1OC
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCN(CC)CCNC(=O)c1ccc(NS(C)(=O)=O)cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.2 %

Procedure:
150 mg (0.36 mmol) of N-(2-diethylamino-ethyl)-4-(bismethanesulfonylamino)-2-methoxy-benzamide is dissolved in 10 ml of tetrahydrofuran and mixed with 1 ml of 1N potassium hydroxide solution. It is stirred for 2 hours at room temperature. Then, the tetrahydrofuran is drawn off in a vacuum, mixed with 25 ml of saturated sodium bicarbonate solution and shaken out three times with 25 ml each of methylene chloride. The collected organic phase is dried, filtered and concentrated by evaporation, and 114 mg (91.9% of theory) of N-(2-diethylamino-ethyl)-4-(methanesulfonylamino)-2-methoxy-benzamide is obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:20])[CH2:11][NH:12][C:13](=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:6][CH:5]=1)([O-:3])=[O:2]>O=P(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[O:20][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:12][CH:11]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CCOC(=O)C(=O)NCC(=O)c1ccc([N+](=O)[O-])cc1
Solvent: O=P(Cl)(Cl)Cl
Product: CCOC(=O)c1ncc(-c2ccc([N+](=O)[O-])cc2)o1
Yield: 60.6 %

Procedure:
A solution of Ethyl 2-(2-(4-nitrophenyl)-2-oxoethylamino)-2-oxoacetate (step C product, 8.5 g) in POCl3 (55 ml) was refluxed for 6 hours. The reaction mixture was cooled, quenched with ice and neutralized with sodium carbonate. DCM was added to it and the organic and aqueous layers were separated. Organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to get dark brown residue. The residue was chromatographed on silica gel in 2:8 Ethyl acetate:Pet ether to get pale brown colored solid which was crystallized in chloroform/pet ether to yield 4.82 g (60%) of the title compound. 1HNMR (CDCl3, 300 MHz): δ 8.41 (d, 2H), 7.97 (d, 2H), 7.37 (s, 1H), 4.55 (q, 2H), 1.49 (t, 3H).
Reaction SMILES: [CH3:1][C:2]([C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)([CH2:5][CH3:6])[CH2:3][CH3:4].C(O)C>[Rh].C(O)(=O)C>[CH3:1][C:2]([CH:7]1[CH2:8][CH2:9][CH:10]([OH:13])[CH2:11][CH2:12]1)([CH2:5][CH3:6])[CH2:3][CH3:4]
Reactant: CCC(C)(CC)c1ccc(O)cc1
Agent: [Rh]
Solvent: CCO
Solvent: CC(=O)O
Product: CCC(C)(CC)C1CCC(O)CC1
Yield: 93 %

Procedure:
A mixture of the 4-(3-methylpent-3-yl)phenol (365 g, 2.05 mol), ethanol (600 g), acetic acid (5.0 g) and 5% rhodium on carbon (8.0 g) was hydrogenated at 100 psi and 60° C. until the hydrogen absorption essentially ceased. The reaction mixture was filtered to remove the catalyst and the solvent was removed on a rotary evaporator. The resulting oil was washed with 10% sodium bicarbonate (200 ml) and then with water (200 ml portions) until a neutral pH (7) was indicated. Distillation of the crude oil under vacuum gave the desired 4-(3-methylpent-3-yl)cyclohexanol: 350 g, 93% yield; bp 110°-115° C. (2.0 mm); mol wt 184 (ms); nmr, 0.4-0.9 (9H, methyls), 1.0-1.5 (14H, m, CH2), 2.39 (1H, s, hydroxyl), 4.0 (1H, m, Hα to oxygen); ir, 3350, 2980, 2950, 2890, 1455, 1385, 1075, 1046, 960 cm-1.