Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH2:8][S:9][CH2:10][CH2:11][NH2:12])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:13]([CH:15]=[C:16](OCC)[NH:17][C:18]#[C:19][CH3:20])#[N:14].C(N)C#C.C(C=C(OCC)OCC)#N>>[C:13]([CH:15]=[C:16]([NH:17][CH2:18][C:19]#[CH:20])[NH:12][CH2:11][CH2:10][S:9][CH2:8][C:3]1[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:14]
Reactant: CC#CNC(=CC#N)OCC
Reactant: NCCSCc1ncccc1Cl
Agent: C#CCN
Agent: CCOC(=CC#N)OCC
Product: C#CCNC(=CC#N)NCCSCc1ncccc1Cl

Procedure:
When 2-[(3-chloro-2-pyridyl)methylthio]ethylamine is reacted with 1-cyano-2-ethoxy-2-propynylaminoethylene [prepared from propargylamine and 1-cyano-2,2-bis(ethoxy)-ethylene, which is itself prepared according to the procedure described in J. Am.. Chem. Soc., 71, 47 (1949)], the title product is produced.
Reaction SMILES: [CH3:1][C:2]1([CH3:36])[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[CH2:8][C:9]1[N:10]([CH3:35])[C:11]2[C:16]([N:17]=1)=[C:15]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[N:14]=[C:13]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH2:33][CH3:34])[N:12]=2.[C:37](O)(=[O:41])[C@H:38]([CH3:40])[OH:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:33]([C:25]1[N:24]([C:13]2[N:12]=[C:11]3[C:16]([N:17]=[C:9]([CH2:8][N:3]4[CH2:4][CH2:5][N:6]([C:37](=[O:41])[C@@H:38]([OH:39])[CH3:40])[CH2:7][C:2]4([CH3:1])[CH3:36])[N:10]3[CH3:35])=[C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:14]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=1)[CH3:34]
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCNCC3(C)C)n(C)c2n1
Reactant: C[C@H](O)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCN(C(=O)[C@H](C)O)CC3(C)C)n(C)c2n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 24 %

Procedure:
A mixture of 8-(2,2-dimethylpiperazin-1-ylmethyl)-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.20 mmol), L-Lactic acid (17 μL, 0.22 mmol), HATU (85 mg, 0.22 mmol) and DIPEA (40 μL, 0.23 mmol) in DCM (2 mL) was allowed to stir at r.t. for 16 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 2%) affording 723 as a white solid (27 mg, 29%). LCMS (method I): RT 2.90 min, [M+H]+ 562.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-8.00 (1 H, m), 7.78-7.74 (1 H, m), 7.35-7.25 (2 H, s), 4.46-4.43 (1 H, m), 4.34 (4 H, brd s), 4.06-3.94 (1 H, m), 3.91 (3 H, s), 3.86 (4 H, t, J=4.68 Hz), 3.76-3.75 (2 H, m), 3.50-3.48 (1 H, m), 3.37-3.35 (3 H, m), 3.24-3.22 (1 H, m), 2.59-2.53 (2 H, m), 1.45 (3 H, t, J=7.48 Hz), 1.34-1.30 (4 H, m), 1.26-1.15 (5 H, m)
Reaction SMILES: [C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:10][N:11]([CH3:15])[CH2:12][CH2:13]Cl.O>C1(C)C=CC=CC=1>[CH3:10][N:11]([CH3:15])[CH2:12][CH2:13][CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]#[N:9]
Reactant: CN(C)CCCl
Reactant: N#CCc1ccccc1
Solvent: O
Solvent: Cc1ccccc1
Product: CN(C)CCC(C#N)c1ccccc1
Yield: 21.9 %

Procedure:
To a refluxing suspension of 35 g (0.90 mol) of NaNH2 in 750 ml of toluene was added, dropwise with mechanical stirring under N2, 100 g (0.85 mol) of phenylacetonitrile in 100 ml of toluene. The resulting suspension was stirred at reflux for a further 3 hr. Then, 92.5 g (0.86 mol) of 2-dimethylaminoethyl chloride in 50 ml of toluene was added dropwise, and the resulting dark suspension was first heated at reflux for 41/2 hr and then stirred at RT for 16 hr. Water (1.5 liters) was added to the mixture, and the organic layer was separated and extracted with 1N HCl. The acid extract was cooled in ice and then basified with 2.5N NaOH. The product was extracted from the basified solution with Et2O. The ethereal extract was dried (Na2SO4) and concentrated by evaporation. Distillation of the resulting crude oil afforded 35 g (52.5%) of the desired 4-dimethylamino-2-phenylbutanenitrile as a colorless oil; bp 95°-98°/0.1 mm.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.FC(F)(F)S(O[C:59]1[CH:64]=[CH:63][C:62]([CH2:65][C:66]([O:68][CH3:69])=[O:67])=[CH:61][CH:60]=1)(=O)=O.[C:72]([O:76][C:77]([N:79]1[CH2:84][CH2:83][NH:82][CH2:81][CH2:80]1)=[O:78])([CH3:75])([CH3:74])[CH3:73]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:72]([O:76][C:77]([N:79]1[CH2:84][CH2:83][N:82]([C:59]2[CH:64]=[CH:63][C:62]([CH2:65][C:66]([O:68][CH3:69])=[O:67])=[CH:61][CH:60]=2)[CH2:81][CH2:80]1)=[O:78])([CH3:75])([CH3:73])[CH3:74]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: COC(=O)Cc1ccc(OS(=O)(=O)C(F)(F)F)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: COC(=O)Cc1ccc(N2CCN(C(=O)OC(C)(C)C)CC2)cc1
Yield: 50.8 %

Procedure:
A flask charged with cesium carbonate (4.6 g, 14.0 mmol), palladium (II) acetate (0.07 g, 0.3 mmol), and (S)-BINAP (0.28 g, 4.5 mmol) was evacuated and flushed with dry nitrogen. Methyl 2-{4-[(trifluoromethyl)sulfonyloxy]phenyl}acetate (3.0 g, 10.0 mmol) and t-butyl-1-piperazinecarboxylate (2.3 g, 12.0 mmol) in 20 mL toluene was added via syringe and the resultant mixture was stirred at ambient temperature for 30 minutes and at 80° C. for 16 hours. The reaction mixture was removed from the heating bath, concentrated, and chromatographed on silica gel (0 to 30% ethyl acetate/hexane) providing 1.7 g (50%) of the title compound. 1H NMR (300 MHz, CDCl3) δ7.20 (d, J=8.5 Hz, 2H), 6.89 (d, J=8.4 Hz, 2H), 3.70 (s, 3H), 3.59 (t, J=5.0 Hz, 4H), 3.57 (s, 2H), 3.12 (t, J=5.2 Hz, 4H), 1.50 (s, 9H); ESI (M+H)+=335.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21]([OH:23])=O)[CH:17]=2)[CH3:14])(=[O:12])=[O:11])=[C:5]([CH3:24])[CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.Cl.[CH3:39][NH:40][CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[NH:49][CH2:50][CH2:51][CH2:52][N:53]=2)=[CH:44][CH:43]=1.CCN(C(C)C)C(C)C>ClCCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:24])[C:6]([S:10]([N:13]([CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21]([N:40]([CH3:39])[CH2:41][C:42]3[CH:43]=[CH:44][C:45]([C:48]4[NH:53][CH2:52][CH2:51][CH2:50][N:49]=4)=[CH:46][CH:47]=3)=[O:23])[CH:17]=2)[CH3:14])(=[O:12])=[O:11])=[C:7]([CH3:9])[CH:8]=1
Reactant: CNCc1ccc(C2=NCCCN2)cc1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)O)co2)c(C)c1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)N(C)Cc3ccc(C4=NCCCN4)cc3)co2)c(C)c1

Procedure:
The title compound was prepared according to general procedure AE using 5-({[(4-Methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)furan-3-carboxylic acid (60 mg, 0.16 mmol), CDI (48 mg, 0.29 mmol), N-methyl-1-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]methanamine dihydrochloride (42 mg, 0.15 mmol) and DIPEA (0.17 mL, 0.97 mmol) in DCE (2 mL).
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:15]=2)[N:8]=1)=O.[C:25]1([NH:35]N)[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1>CN(C=O)C.C(O)(=O)C>[CH3:23][S:20]([C:16]1[CH:15]=[C:14]([N:9]2[CH:10]=[CH:11][C:12](=[O:13])[C:7]([C:5]3[N:35]([C:25]4[C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[CH:28]=[CH:27][CH:26]=4)[N:2]=[CH:3][CH:4]=3)=[N:8]2)[CH:19]=[CH:18][CH:17]=1)(=[O:22])=[O:21]
Reactant: NNc1cccc2ccccc12
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(S(C)(=O)=O)c2)ccc1=O
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1cccc(-n2ccc(=O)c(-c3ccnn3-c3cccc4ccccc34)n2)c1

Procedure:
3-((E)-3-dimethylamino-acryloyl)-1-(3-methansulfonyl-phenyl)-1H-pyridazin-4-one (A-7) and naphthalen-1-yl-hydrazine (2 eq) were dissolved in a sealed tube in DMF with 2 drops acetic acid and irradiated in MW at 120° C. for 15 min. The solvent of the reaction mixture was removed and the crude product was purified by preparative HPLC yielding the desired product.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][C@@H:5]([CH:7]2[CH2:9][N@@:8]2[S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])[O:4][C:3]1=[O:22].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[CH2:35][C:34]([CH3:37])([CH3:36])[NH:33][CH2:32][C:31]1=[O:38]>C1(C)C=CC=CC=1>[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[C:31](=[O:38])[CH2:32][N:33]([CH2:9][C@H:7]([NH:8][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])[C@@H:5]2[CH2:6][C@@H:2]([CH3:1])[C:3](=[O:22])[O:4]2)[C:34]([CH3:37])([CH3:36])[CH2:35]1
Reactant: C[C@@H]1C[C@@H](C2C[N@@]2S(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Reactant: CC1(C)CN(c2ccccc2Cl)C(=O)CN1
Agent: C[C@@H]1C[C@@H](C2C[N@]2S(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Solvent: Cc1ccccc1
Product: C[C@@H]1C[C@@H]([C@H](CN2CC(=O)N(c3ccccc3Cl)CC2(C)C)NS(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Yield: 94.1 %

Procedure:
A solution of 822 mg of (3R,5S)-3-methyl-5-[(S)-1-(2-nitrobenzenesulfonyl)aziridin-2-yl]dihydrofuran-2-one obtained in Example (76g) (2.52 mmol) and 722 mg of 1-(2-chlorophenyl)-5,5-dimethylpiperazin-2-one obtained in Example (1k) (3.02 mmol) in toluene (25 ml) was stirred at 110° C. for two hours. After cooling, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/ethyl acetate=3/1-2/1) to obtain 1.34 g of the title compound (yield: 94%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([OH:16])[CH:12]=2)[N:7]=1)=[O:5])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:36]([N:39]1[CH2:43][CH2:42][CH:41](O)[CH2:40]1)([CH3:38])[CH3:37]>C1(C)C=CC=CC=1.C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][CH:41]3[CH2:42][CH2:43][N:39]([CH:36]([CH3:38])[CH3:37])[CH2:40]3)[CH:12]=2)[N:7]=1)=[O:5])[CH3:2]
Reactant: CC(C)N1CCC(O)C1
Reactant: CCOC(=O)c1ccc2cc(O)ccc2n1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc2cc(OC3CCN(C(C)C)C3)ccc2n1
Temperature: 35 °C

Procedure:
A mixture of 0.960 g (0.0044 mol) of 6-hydroxy-quinoline-2-carboxylic acid ethyl ester, 2.32 g (0.0088 mmol) of triphenylphospine (Fluka), 0.739 g (0.0057 mmol) of 1-isopropyl-3-pyrrolidinol and 1.61 ml (0.0088 mmol) of di-tert.-butyl azadicarboxylate 40% in toluene in 100 ml THF was stirred for a prolonged period of time at 35° C. The mixture was filtered through a pad of silica and washed with 30 ml of THF. The mixture was evaporated to dryness and purified on silica eluting with a gradient of DCM/MeOH 98/2. The product fractions were evaporated and the residue was triturated with diethyl ether to yield after drying under vacuum 1.35 g (94%) of the title compound as white solid. MS (m/e): 329.3 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=O)[C:5]([OH:11])=[CH:4][CH:3]=1.[F:12][C:13]([F:26])([F:25])[C:14]1[CH:15]=[C:16]([CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1)[NH2:17]>>[F:12][C:13]([F:25])([F:26])[C:14]1[CH:15]=[C:16]([NH:17][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[OH:11])[CH:18]=[C:19]([C:21]([F:22])([F:24])[F:23])[CH:20]=1
Reactant: O=C(O)c1cc(Cl)ccc1O
Reactant: Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Product: O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cc(Cl)ccc1O
Yield: 85.5 %

Procedure:
Using 5-chlorosalicylic acid and 3,5-bis(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([CH:18]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([O:16]C)[CH:11]=1)=[O:8].[Si](I)(C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([CH:18]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][NH:13][C:12](=[O:16])[CH:11]=1)=[O:8]
Reactant: COc1cc(NC(=O)c2cc(Cl)ccc2F)ccn1
Agent: C[Si](C)(C)I
Solvent: CC#N
Product: O=C(Nc1cc[nH]c(=O)c1)c1cc(Cl)ccc1F
Temperature: 50 °C
Reaction time: 8 h
Yield: 26.4 %

Procedure:
To 5-chloro-2-fluoro-N-(2-methoxy-4-pyridyl)benzamide (3.8 g, 13.50 mmol) in acetonitrile (126.3 mL) was added TMSI (7.7 mL, 54.00 mmol). The reaction was stirred at 50° C. overnight. The acetonitrile was evaporated and the crude re-dissolved in ethyl acetate. The organics were washed with water, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography using a gradient of ethyl acetate in hexanes (0-100%) and then methanol in dichloromethane (0-20%) yielded 5-chloro-2-fluoro-N-(2-oxo-1H-pyridin-4-yl)benzamide (950 mg, 26%) as a white solid. ESI-MS m/z calc. 266.03. found 267.1 (M+1)+; Retention time: 1.24 minutes (3 minutes run).
Reaction SMILES: Cl.[C:2]([NH:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([OH:17])[CH:11]=1)=[O:9])([CH3:5])([CH3:4])[CH3:3].C[O-].[Na+].[C:21]1([CH3:28])[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=1>CN(C)C=O>[ClH:27].[C:2]([NH:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][C:23]2[CH:22]=[C:21]([CH3:28])[CH:26]=[CH:25][CH:24]=2)=[C:12]([OH:17])[CH:11]=1)=[O:9])([CH3:5])([CH3:3])[CH3:4]
Reactant: CC(C)(C)NCC(=O)c1ccc(O)c(O)c1
Reactant: Cc1cccc(Cl)c1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cccc(Oc2ccc(C(=O)CNC(C)(C)C)cc2O)c1

Procedure:
Using a procedure similar to that described above in Example 58A, 13 g. of 3,4-dihydroxyphenyl tert-butylaminomethyl ketone hydrochloride was reacted with 8 g. of sodium methoxide in 200 ml. of N,N-dimethylformamide under an atmosphere of nitrogen and then 8 g. of m-toluyl chloride was added to produce 3-hydroxy-4-(m-toluyloxy)phenyl tert-butylaminomethyl ketone hydrochloride. This salt was converted to the free base which was treated with acetic acid to yield 11.5 g. of the acetate salt, m.p. 170°-175° C. By treating a slurry of this salt in 100 ml. of N,N-dimethylformamide with 40 g. of methanesulfonic acid there was obtained 10.6 g. of the corresponding methanesulfonate salt, m.p. >250° C. (uncorr.). This methanesulfonate (10 g.) was catalytically hydrogenated, using a procedure similar to that described above in Example 30B, to yield 5.4 g. of 3-hydroxy-4-(m-toluyloxy)-alpha-(tert-butylaminomethyl)benzyl alcohol methanesulfonate as a white crystalline solid which melted at 165°-168° C. (uncorr.).
Reaction SMILES: [CH3:1][NH:2][CH3:3].Cl[C:5]1[CH:10]=[C:9]([Cl:11])[N:8]=[C:7]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:6]=1>O1CCCC1.C(N(CC)C(C)C)(C)C>[Cl:11][C:9]1[N:8]=[C:7]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:6]=[C:5]([N:2]([CH3:3])[CH3:1])[CH:10]=1
Reactant: CNC
Reactant: Clc1cc(Cl)nc(Nc2ccccc2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CN(C)c1cc(Cl)nc(Nc2ccccc2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
Dimethylamine in tetrahydrofuran (2M, 15 mL) was added to a solution of 4,6-dichloro-N-phenyl-2-pyrimidinamine (0.715 g, 2.97 mmol) in tetrahydrofuran (30 mL) and N,N-diisopropylethylamine (0.52 mL). The resulting mixture was stirred at room temperature overnight. The solvent was removed and the crude material was purified by flash chromatography on silica gel, eluting with ethyl acetate/hexane (1:9). The eluent was removed, giving 6-chloro-N4,N4-dimethyl-N2-phenyl-2,4-pyrimidinediamine (0.592 g, 2.39 mmol, 80%, Rf=0.3).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[S:18][C:17]([C:19](=O)[CH2:20][CH2:21][C:22]([OH:24])=O)=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.O.[NH2:27][NH2:28]>O>[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[S:18][C:17]([C:19]3[CH2:20][CH2:21][C:22](=[O:24])[NH:27][N:28]=3)=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: NN
Reactant: O=C(O)CCC(=O)c1ccc(CCCCCCCCn2ccnc2)s1
Solvent: O
Product: O=C1CCC(c2ccc(CCCCCCCCn3ccnc3)s2)=NN1
Temperature: 90 °C
Reaction time: 2 h

Procedure:
1.8 g of 4-{5-[8-(1-Imidazolyl)-octyl]-thien-2-yl}-4-oxo-butyric acid are suspended in 10 ml of water, 0.26 g of hydrazine hydrate are added and the mixture is stirred at 90° C. for 2 hours. After the mixture has been cooled, the precipitate formed is filtered off with suction, washed with water and dried.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][C@@H:12]([CH3:16])[CH2:13][O:14][CH3:15])[CH:10]=1)[C:5]([OH:7])=[O:6].F[C:18]1[CH:29]=[CH:28][C:21]2[C:22](=[O:27])[N:23]([CH3:26])[CH2:24][O:25][C:20]=2[CH:19]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C(#N)C>[CH3:16][C@H:12]([O:11][C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([O:1][C:18]2[CH:29]=[CH:28][C:21]3[C:22](=[O:27])[N:23]([CH3:26])[CH2:24][O:25][C:20]=3[CH:19]=2)[CH:10]=1)[C:5]([OH:7])=[O:6])[CH2:13][O:14][CH3:15]
Reactant: CN1COc2cc(F)ccc2C1=O
Reactant: COC[C@H](C)Oc1cc(O)cc(C(=O)O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: COC[C@H](C)Oc1cc(Oc2ccc3c(c2)OCN(C)C3=O)cc(C(=O)O)c1
Temperature: 160 °C
Reaction time: 16 h
Yield: 80.5 %

Procedure:
A mixture of 3-hydroxy-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid (175 mg, 0.77 mmol), 7-fluoro-3-methyl-2,3-dihydro-4H-1,3-benzoxazin-4-one (141 mg, 0.77 mmol) and potassium carbonate (321 mg, 2.32 mmol) in acetonitrile (5 mL) was stirred in a microwave reactor at 160° C. for 16 hours then reduced in vacuo and ethyl acetate (50 mL) added. The mixture was washed with water (50 mL), the aqueous layer acidified with 1M citric acid and extracted into ethyl acetate (2×50 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), and reduced in vacuo to give the desired compound as a brown oil (0.24 g). m/z 453 (M+H)+
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]([OH:24])[CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.[CH3:25][O:26][C:27](=[O:45])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=1>>[CH3:25][O:26][C:27](=[O:45])[CH2:28][CH2:29][C:30]1[CH:35]=[C:34]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[O:12][N:11]=[C:10]([CH3:13])[C:9]=3[CH:14]([OH:24])[CH2:15][CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:4][CH:3]=2)[CH:33]=[CH:32][CH:31]=1
Reactant: COC(=O)CCc1cccc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(O)CCCc1ccccc1
Product: COC(=O)CCc1cccc(-c2ccc(-c3onc(C)c3C(O)CCCc3ccccc3)cc2)c1

Procedure:
Prepared according to the procedure described in Example 110, Step 3, using 1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-4-phenyl-butan-1-ol and 3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionic acid methyl ester.
Reaction SMILES: C([O:8][C:9](=[O:47])[CH2:10][N:11]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:14](=[O:28])[CH:13]([CH2:29][C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([C:39](OC(C)(C)C)=O)[N:31]=2)[C:12]1=[O:46])C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[CH3:39][N:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:30]([CH2:29][CH:13]2[C:12](=[O:46])[N:11]([CH2:10][C:9]([OH:47])=[O:8])[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[N:15]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:14]2=[O:28])=[N:31]1
Reactant: CC(C)(C)OC(=O)n1nc(CC2C(=O)N(CC(=O)OCc3ccccc3)c3ccccc3N(c3ccccc3)C2=O)c2ccccc21
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cn1nc(CC2C(=O)N(CC(=O)O)c3ccccc3N(c3ccccc3)C2=O)c2ccccc21
Yield: 101.8 %

Procedure:
tert-butyl 3-({1-[2-(benzyloxy)-2-oxoethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H -1,5-benzodiazepin-3-yl}methyl)-1H-indazole-1-carboxylate (0.6 g, 0.95 mM) were dissolved in 10 ml of ethyl acetate and 50 mg of 10% Pd/C were added. Reaction mixture was hydrogenated at atm. Pressure overnight. Catalyst was removed by filtration and was solvent evaporated under reduced pressure. 0.44 g of product was obtained.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[O:6][C@@H:5]([C@H:7]2[O:11][C@@H:10]3[O:12][C:13]([CH3:16])([CH3:15])[O:14][C@@H:9]3[C@H:8]2[OH:17])[CH2:4][O:3]1.CS(C)=O.C(OC(=O)C)(=O)C>>[CH3:1][C:2]1([CH3:18])[O:6][C@@H:5]([C@H:7]2[O:11][C@@H:10]3[O:12][C:13]([CH3:16])([CH3:15])[O:14][C@@H:9]3[C@@H:8]2[OH:17])[CH2:4][O:3]1
Reactant: CC1(C)O[C@H]2O[C@H]([C@H]3COC(C)(C)O3)[C@H](O)[C@H]2O1
Solvent: CS(C)=O
Solvent: CC(=O)OC(C)=O
Product: CC1(C)O[C@H]2O[C@H]([C@H]3COC(C)(C)O3)[C@@H](O)[C@H]2O1
Yield: 58 %

Procedure:
The surprising finding according the present invention is that it is possible to carry out the oxidation of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose with DMSO/acetic anhydride in one pot with the subsequent reduction of the 1,2:5,6-di-O-isopropylidene-α-D-ribofuranose-3-ulose to form 1,2:5,6-di-O-isopropylidene-α-D-allofuranose (formula I). It is very surprising that the reduction can be carried out in the presence of the oxidation mixture. It is also surprising that it is possible to use this oxidation procedure in large scale (1 mole), and that the lowest reported amount of excess acetic anhydride (5 times) provides 58 % yield of recrystallised and analytical pure 1,2:5,6-di-O-isopropylidene-α-D-allofuranose.
Reaction SMILES: [NH2:1][C@@H:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9]OC(=O)CC(=O)C)[CH2:7][S:8][C@H:3]12.C(=O)([O-])O.[Na+].[SH:27][C:28]1[S:29][C:30]([CH3:33])=[N:31][N:32]=1>O>[NH2:1][C@@H:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][S:27][C:28]3[S:29][C:30]([CH3:33])=[N:31][N:32]=3)[CH2:7][S:8][C@H:3]12
Reactant: CC(=O)CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: Cc1nnc(S)s1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Cc1nnc(SCC2=C(C(=O)O)N3C(=O)[C@@H](N)[C@H]3SC2)s1
Temperature: 60 °C
Reaction time: 1 h
Yield: 84.3 %

Procedure:
In water (30 ml) was dissolved 7β-amino-3-(3-oxobutyryloxy)methyl-3-cephem-4-carboxylic acid (3.14 g) together-with sodium hydrogen carbonate (1.84 g) and 2-mercapto-5-methyl-1,3,4-thiadiazole (1.6 g) and the resultant solution was adjusted its pH to 6.4, followed by stirring for one hour at 60° C. After cooling, the reaction solution was washed with dichloromethane and pH of the aqueous layer was adjusted to 3.5 under ice-cooling, followed by stirring for one hour. The precipitated materials were collected by filtration and washed with water, methanol and acetone in this order, followed by drying to give 7β-amino-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (2.9 g).