Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]=1[NH2:12].N1C=CC=CC=1.Cl[S:20]([C:23]1[N:31]=[C:30]2[N:25]([C:26]([O:33][CH2:34][CH3:35])=[N:27][C:28]([F:32])=[CH:29]2)[N:24]=1)(=[O:22])=[O:21]>ClCCl>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]=1[NH:12][S:20]([C:23]1[N:31]=[C:30]2[N:25]([C:26]([O:33][CH2:34][CH3:35])=[N:27][C:28]([F:32])=[CH:29]2)[N:24]=1)(=[O:21])=[O:22]
Reactant: COC(=O)c1cccc(Cl)c1N
Reactant: CCOc1nc(F)cc2nc(S(=O)(=O)Cl)nn12
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOc1nc(F)cc2nc(S(=O)(=O)Nc3c(Cl)cccc3C(=O)OC)nn12
Temperature: 10 °C
Reaction time: 6 h
Yield: 90 %

Procedure:
The same product was obtained in a similar fashion using the N-(2-chloro-6-methoxycarbonylphenyl)-S,S-tetramethylenesulfilimine product mixture of Example 4 as the catalyst. A 9 mL portion of that product was diluted with 75 mL of dichloromethane, the solution was cooled to 10° C., and 9.3 g (50 mmol) of methyl 3-chloroanthranilate and then 4.8 g (60 mmol) of pyridine were added with cooling and stirring. 2-Chlorosulfonyl-7-fluoro-5-ethoxy[1,2,4]triazolo[1,5-c]pyrimidine (15.5 g of 91 percent pure, 50 mmol) was added with cooling to 0-2° C. The reaction was complete in 6 hours and a 90 percent yield of 98 percent purity title compound was obtained on recovery.
Reaction SMILES: [O:1]=[S:2]1(=[O:32])[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:4]([C:12]2[C:13](=[O:31])[N:14]([N:23]=[CH:24][C:25]3[N:26]=[C:27]([CH3:30])[S:28][CH:29]=3)[C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:3]1.CO.[BH4-].[Li+].Cl>O1CCCC1.O>[O:32]=[S:2]1(=[O:1])[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:4]([C:12]2[C:13](=[O:31])[N:14]([NH:23][CH2:24][C:25]3[N:26]=[C:27]([CH3:30])[S:28][CH:29]=3)[C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:3]1
Reactant: Cc1nc(C=Nn2c(=O)c(C3=NS(=O)(=O)c4ccccc4N3)c(O)c3ccccc32)cs1
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: Cc1nc(CNn2c(=O)c(C3=NS(=O)(=O)c4ccccc4N3)c(O)c3ccccc32)cs1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
The product of Example 232A (0.097 g, 0.208 mmol) in tetrahydrofuran (5 mL) and methanol (0.016 mL, 0.40 mmol) at 0° C. was treated with dropwise addition of a 2.0M solution of lithium borohydride in tetrahydrofuran (0.15 mL, 0.3 mmol). The reaction was stirred at 25° C. for 3 hour, acidified with 1M hydrochloric acid to a pH of approximately 2-4, diluted with water (10 mL), and the resulting precipitate was collected by filtration and dried. The crude product was chromatographed on C-18 reverse phase column eluting with water:acetonitrile 90:10-0:100 to give the title compound. The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.68 (s, 3 H) 3.24 (m, 2 H) 6.33 (m, 1 H) 7.10 (m, 1 H) 7.31 (m, 2 H) 7.43 (s, 1 H) 7.61 (m, 4 H) 8.08 (d, J=7.72 Hz, 1 H) 16.24 (s, 1 H). MS (ESI−) (M−H)− m/z 466.
Reaction SMILES: C(OC([NH:8][CH:9]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=1)[CH2:10][NH:11][S:12]([NH:15]C(=O)OC(C)(C)C)(=[O:14])=[O:13])=O)(C)(C)C.Cl.C(=O)([O-])O.[Na+]>ClCCl.O1CCOCC1.C(OCC)(=O)C>[NH2:8][CH:9]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=1)[CH2:10][NH:11][S:12](=[O:13])(=[O:14])[NH2:15]
Reactant: CC(C)(C)OC(=O)NC(CNS(=O)(=O)NC(=O)OC(C)(C)C)c1cccc(C(F)(F)F)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: NC(CNS(N)(=O)=O)c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 100 mg (0.20 mmol) of the compound from Example 133A in 2 ml of dichloromethane was admixed with 2 ml of a 4M solution of hydrogen chloride in dioxane, and the mixture was stirred at RT for 2 h. It was diluted with ethyl acetate and admixed with 10% strength aqueous sodium hydrogen carbonate solution. The alkaline aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulphate and freed from the solvents on a rotary evaporator. The residue was the title compound (53 mg, 92% of theory).
Reaction SMILES: [NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]([CH3:44])([O:33][Si:34]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:40])[CH3:39])[CH:35]([CH3:37])[CH3:36])[CH3:32])[CH2:27][CH2:26]3)=[N:23][N:24]=2)[CH:21]=1.N>CN(C=O)C.CO.C(Cl)Cl>[CH3:32][C:31]([CH:28]1[CH2:27][CH2:26][N:25]([C:22]2[N:20]3[CH:21]=[C:16]([O:12][C@H:5]4[C:6]5[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=5)[C@@H:2]([NH2:1])[CH2:3][CH2:4]4)[CH:17]=[CH:18][C:19]3=[N:24][N:23]=2)[CH2:30][CH2:29]1)([O:33][Si:34]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:39])[CH3:40])[CH:35]([CH3:36])[CH3:37])[CH3:44]
Reactant: N[C@H]1CC[C@@H](O)c2ccccc21
Reactant: CC(C)[Si](OC(C)(C)C1CCN(c2nnc3ccc(F)cn23)CC1)(C(C)C)C(C)C
Agent: N
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)[Si](OC(C)(C)C1CCN(c2nnc3ccc(O[C@@H]4CC[C@H](N)c5ccccc54)cn23)CC1)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 30.2 %

Procedure:
To a solution of Intermediate A (129 mg, 0.788 mmol) in dry DMF (2 mL) at RT under Ar was added NaH (60% dispersion in oil, 45.0 mg, 1.13 mmol) (CARE: gas evolution) and the resulting opaque brown solution stirred at RT for 45 min. A solution of Intermediate 74b (326 mg, 0.750 mmol) in dry DMF (2 mL) was added and the resulting dark brown solution stirred at 60° C. for 2.5 h. The solution was concentrated in vacuo, redissolved in MeOH (2 mL) and AcOH (0.100 mL), applied to an SCX-2 cartridge and washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo gave a viscous dark brown oil. FCC, using 1-6% [2M NH3 in MeOH] in DCM, gave the title compound as a viscous brown oil (131 mg, 30%). LCMS (Method 3): Rt 3.53 min, m/z 578 [MH+].
Reaction SMILES: Br[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH:74]1[CH2:78][CH2:77][CH2:76][CH2:75]1>C1(C)C=CC=CC=1.CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:74]1([C:2]2[C:3]([O:8][C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=4)=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:78][CH2:77][CH2:76][CH2:75]1
Reactant: Brc1cccnc1Oc1ccc(Nc2ccccn2)cc1
Reactant: C1CCNC1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: CO
Product: c1ccc(Nc2ccc(Oc3ncccc3N3CCCC3)cc2)nc1
Temperature: 95 °C

Procedure:
A mixture of N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine (300 mg, 0.88 mmol), rac-BINAP (109 mg, 0.17 mmol), Pd2(dba)3 (80 mg, 0.088 mmol), Cs2CO3 (857 mg, 2.6 mmol) and pyrrolidine (1.31 mmol) in toluene (3.5 mL) was heated to 95° C. for 18 h. The mixture was cooled to room temperature, diluted with MeOH and filtered through Celite. The filtrate was concentrated, dissolved in MeOH and purified with reverse-phase HPLC (Phenomenex Gemini 80 A column, 100×50 mm, 80 ml/min, 10-95% CH3CN/H2O, 0.1% TFA, 15 min gradient). The residue was re-purified by column chromatography (EtOAc/Hexanes=0-40%, followed by recrystallization from MeOH to give the title compound. MS (ESI, pos. ion) m/z: 333 (M+1). IC50 (uM) 0.063.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][CH2:20][C:21]([NH:23][C:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=2[C:30](O)=[O:31])=O)[CH2:13][CH2:12]1.C(OC(=O)C)(=O)C.[CH3:40][NH2:41].CO>O1CCCC1>[CH3:40][N:41]1[C:30](=[O:31])[C:25]2[CH2:26][CH2:27][CH2:28][CH2:29][C:24]=2[N:23]=[C:21]1[CH2:20][CH2:19][CH2:18][CH2:17][N:14]1[CH2:15][CH2:16][N:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=2)[CH2:12][CH2:13]1
Reactant: O=C(CCCCN1CCN(c2ccc3ccccc3n2)CC1)NC1=C(C(=O)O)CCCC1
Reactant: CN
Solvent: CC(=O)OC(C)=O
Solvent: CO
Solvent: C1CCOC1
Product: Cn1c(CCCCN2CCN(c3ccc4ccccc4n3)CC2)nc2c(c1=O)CCCC2
Temperature: 25 °C
Yield: 89.3 %

Procedure:
In 30 ml of tetrahydrofuran, 10.0 g of 2-[5-(4-quinolin-2-ylpiperazin-1-yl)-pentanoylamino]cyclohex-1-enecarboxylic acid as synthesized in above Step 7-1-E was suspended, and to the suspension, 7.0 g of 3 equivalent of acetic anhydride was added, followed by an hour's heating under reflux. The solution was cooled with ice, and while continuing the cooling, 35.6 ml of excessive 40% methylamine-methanol solution was gradually added. After about 10 minutes' refluxing under stirring, the temperature was cooled to room temperature and the solution was concentrated under reduced pressure. After addition of 80 ml of distilled water and 30 minutes' stirring, precipitated crystals were recovered by filtration and dried to provide 8.83 g (89.3%) of 3-methyl-2-[4-(4-quinolin-2-ylpiperazin-1-yl)butyl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one.
Reaction SMILES: [N+]([O-])(O)=O.[N+]([O-])(O)=O.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([NH:23][C:24]([NH2:26])=[NH:25])[CH:14]=[CH:15][C:16]=1[N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]1.[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=O)[C:35]#[C:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:30][CH:29]=1.C[O-].[Na+].O>C(#N)C>[CH2:37]([C:36]1[CH:35]=[C:34]([C:31]2[CH:30]=[CH:29][C:28]([Cl:27])=[CH:33][CH:32]=2)[N:26]=[C:24]([NH:23][C:13]2[CH:14]=[CH:15][C:16]([N:17]3[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]3)=[C:11]([O:10][CH3:9])[CH:12]=2)[N:25]=1)[CH2:38][CH2:39][CH3:40]
Reactant: CCCCC#CC(=O)c1ccc(Cl)cc1
Reactant: COc1cc(NC(=N)N)ccc1-n1cnc(C)c1
Agent: C[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O=[N+]([O-])O
Solvent: O
Product: CCCCc1cc(-c2ccc(Cl)cc2)nc(Nc2ccc(-n3cnc(C)c3)c(OC)c2)n1
Temperature: 120 °C
Yield: 16.3 %

Procedure:
A suspension of N-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-guanidine dinitrate (153 mg, 0.41 mmol), 1-(4-chloro-phenyl)-hept-2-yn-1-one (100 mg, 0.45 mmol, CAS 105363-17-5) and sodium methanolat (120 mg, 1.24 mmol) in acetonitrile (2.0 mL) was heated two times to 120° C. for 30 minutes in a microwave oven. Water was added and the reaction was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography on silica gel using dichloromethane/methanol (9:1 v/v) as eluent to yield the title compound as a yellow solid (30 mg, 16%). MS ISP (m/e): 448.3/450.1 (100/37) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.04 (d, 2H), 7.98 (s, 1H), 7.64 (s, 1H), 7.46 (d, 2H), 7.29 (s, 1H), 7.18 (d, 1H), 7.04 (d, 1H), 6.89 (s, 1H), 3.89 (s, 3H), 2.74 (t, 2H), 2.31 (, 3H), 1.79 (m, 2H), 1.43 (m, 2H), 0.98 (t, 3H).
Reaction SMILES: F[B-](F)(F)F.C([O+](CC)CC)C.[C:13]([O:17][C:18](=[O:25])[NH:19][C@H:20]([C:22](=O)[NH2:23])[CH3:21])([CH3:16])([CH3:15])[CH3:14].[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH:32][C:33]1[C:38](N)=[CH:37][CH:36]=[CH:35][N:34]=1>C1COCC1.C(O)C>[C:13]([O:17][C:18](=[O:25])[NH:19][C@H:20]([C:22]1[N:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[C:27]2=[N:26][CH:31]=[CH:30][CH:29]=[C:28]2[N:23]=1)[CH3:21])([CH3:16])([CH3:15])[CH3:14]
Reactant: Nc1cccnc1Nc1ccccn1
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(N)=O
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCO
Product: C[C@H](NC(=O)OC(C)(C)C)c1nc2cccnc2n1-c1ccccn1
Yield: 98.2 %

Procedure:
Triethyloxonium tetrafluoroborate (1.08 g, 5.66 mmol) was added to a solution of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester (1.00 g, 5.33 mmol) in THF (15 mL) at 20° C. under nitrogen and the resultant mixture stirred for 2 h then concentrated in vacuo. A solution of N2-pyridin-2-yl-pyridine-2,3-diamine (0.62 g, 3.33 mmol) in ethanol (15 mL) was added to the residue and the resultant solution stirred at 75° C. for 16 h. The reaction mixture was concentrated in vacuo and the residue partitioned between DCM (3×30 mL) and saturated aqueous NaHCO3 (30 mL). The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by chromatography (SiO2 0-5% (2M ammonia in methanol) in DCM) to give the title compound as an oil (1.11 g, 98%). LCMS (method H): Rt 2.73 min, [M+H]+ 340.
Reaction SMILES: [CH2:1]([NH:4][CH2:5][CH2:6][CH3:7])[CH2:2][CH3:3].C[Al](C)C.[NH2:12][C:13]1[CH2:14][C:15]([C:25]([O:27]CC)=O)=[CH:16][C:17]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:18]=2[N:19]=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1>[NH2:12][C:13]1[CH2:14][C:15]([C:25]([N:4]([CH2:5][CH2:6][CH3:7])[CH2:1][CH2:2][CH3:3])=[O:27])=[CH:16][C:17]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:18]=2[N:19]=1
Reactant: CCCNCCC
Reactant: CCOC(=O)C1=Cc2ccc(Br)cc2N=C(N)C1
Agent: C[Al](C)C
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCCN(CCC)C(=O)C1=Cc2ccc(Br)cc2N=C(N)C1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 34.1 %

Procedure:
A 50 ml round bottom flask equipped with a stir bar and nitrogen inlet was charged with 15 mls of dry toluene and dipropylamine (0.44 ml, 3.24 mmol). This was chilled to 0° C. and AlMe3 (4.04 mls, 8.09 mmol, 2M in toluene) was then added. Once the addition was complete, the mixture was allowed to warm to room temperature (˜20-30 minutes). (1E,4E)-ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate (0.5 g, 1.62 mmol) was then added portionwise resulting in a dark solution. This mixture was warmed to 100° C. for about 16 hours, and then allowed to cool to room temperature. This mixture was then poured into 50 mls of a 30% aq. solution of Rochelle's salt and vigorously stirred for 20 minutes, then extracted with EtOAc (2×), extracts dried over sodium sulfate and concentrated under reduced pressure. Flash 40 Biotage (40M cartridge, 5% MeOH/DCM) afforded 201 mgs (32%) of (1E,4E)-2-amino-8-bromo-N,N-dipropyl-3H-benzo[b]azepine-4-carboxamide. m/z (APCI-pos) M+1=364.2, 366.2.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:21][CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:39][O:40][C:41](=[O:58])[C:42]1[CH:47]=[CH:46][C:45](B2OC(C)(C)C(C)(C)O2)=[CH:44][C:43]=1[F:57].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:39][O:40][C:41](=[O:58])[C:42]1[CH:47]=[CH:46][C:45]([C:20]([C:11]2[N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:8])=[O:9])[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=2)=[CH:21][CH:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[CH:44][C:43]=1[F:57]
Reactant: COC(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1F
Reactant: Cc1ccc(S(=O)(=O)OC(=CC2CCOCC2)c2cc3cc(F)cnc3n2S(=O)(=O)c2ccccc2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)c1ccc(C(=CC2CCOCC2)c2cc3cc(F)cnc3n2S(=O)(=O)c2ccccc2)cc1F
Yield: 74.3 %

Procedure:
To a mixture of toluene-4-sulfonic acid 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-vinyl ester (prepared as in Example 122, 0.57 g, 1 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (prepared as in Example 95, 1.2 g, 4.2 mmol) and dichlorobis(triphenylphosphine)palladium (II) (70 mg, 0.1 mmol) in dioxane (8 mL) was added an aqueous sodium carbonate solution (2 M, 1.25 mL). The resulting mixture was subjected to microwave irradiation for 2 h at 100° C. The mixture was diluted with ethyl acetate (100 mL), washed with a saturated aqueous sodium bicarbonate solution (2×30 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 25% ethyl acetate/hexanes) afforded 4[1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-vinyl]-2-fluoro-benzoic acid methyl ester (400 mg, 72%) as a white solid: LC/MS m/e calcd for C28H24F2N2O5S [M+H]+ 539.57, observed 539.0.
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:27]([CH3:29])[CH3:28])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([NH:16][CH:17]([CH:21]([OH:26])[C:22]([F:25])([F:24])[F:23])[CH:18]([CH3:20])[CH3:19])=[O:15])=[O:8])=[O:4].[Mn]([O-])(=O)(=O)=O.[K+]>CO>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:27]([CH3:29])[CH3:28])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([NH:16][CH:17]([C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])[CH:18]([CH3:20])[CH3:19])=[O:15])=[O:8])=[O:4]
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)NC(C(C)C)C(O)C(F)(F)F)C(C)C
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CO
Product: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)NC(C(=O)C(F)(F)F)C(C)C)C(C)C
Temperature: 10 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
Using a similar oxidation procedure to that described in Example 2, but using (S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutyryl]-N-[2-methyl-1-(2,2,2-trifluoro-1-hydroxyethyl)propyl]-pyrrolidine-2-carboxamide and adding the potassium permanganate solution at 5°-10° C. and then stirring at 10° C. for one hour prior to treatment with methanol, there was obtained (after work-up by extration into tert-butyl methyl ether, followed by washing with brine and concentration in vacuo) (S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutyryl]-N-[2-methyl-1-(2,2,2-trifluoroacetyl)propyl]-pyrrolidine-2-carboxamide as a gum (in 75% yield); SSS:SSR ratio of 53:47; hydrate:ketone 1:1; 1H NMR similar to that of the product of Example 1. [Using a similar procedure, but adding the potassium permanganate solution at ambient temperature instead of 5°-10° C., the product was obtained in a ratio of SSS:SSR of 47:53.]
Reaction SMILES: [O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:9][CH:10]([NH2:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.I[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O)CO>[Cu]I.CCCCCC.C(OCC)(=O)C.CC(O)C>[C:19]1([NH:17][CH:10]([CH3:9])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Ic1ccccc1
Reactant: CC(N)c1ccccc1
Agent: [Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: OCCO
Solvent: CCOC(C)=O
Product: CC(Nc1ccccc1)c1ccccc1
Yield: 73 %

Procedure:
The general procedure under argon was followed using copper(I) iodide (10 mg, 0.05 mmol), K3PO4 (425 mg, 2.00 mmol), α-methylbenzylamine (155 μL, 1.20 mmol), iodobenzene (112 μL, 1.00 mmol), ethylene glycol (111 μL, 2.00 mmol) and 2-propanol (1.0 mL). Column chromatography using a solvent mixture (hexane/ethyl acetate=20/1, Rf=0.5) afforded N-(phenyl)-α-methylbenzylamine (144 mg, 73% isolated yield) as colorless liquid. HPLC conditions: (column: Daicel OD-H; solvent: 10% iPrOH in hexane; flow rate: 0.7 mL/min; UV lamp: 254 nm; retention time: 6.01, 6.78 min). The spectral data (1H NMR) matched with the literature references and GC analysis indicated >95% purity. See Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A. J. Am. Chem. Soc. 1999, 121, 6421-6429.
Reaction SMILES: [H][H].[OH:3][C:4]1[CH:5]=[C:6]([CH2:12][CH2:13][C:14](O)=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].C(OC(=O)C(C)(C)C)(=O)C(C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCCC1>[OH:3][C:4]1[CH:5]=[C:6]([CH2:12][CH2:13][CH:14]=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: COc1ccc(CCC(=O)O)cc1O
Reactant: [H][H]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)C(=O)OC(=O)C(C)(C)C
Solvent: C1CCOC1
Product: COc1ccc(CCC=O)cc1O
Temperature: 80 °C
Reaction time: 24 h
Yield: 48.3 %

Procedure:
Into a chemical reactor for hydrogen addition (hydrogenation) under elevated pressure, 3-(3-hydroxy-4-methoxyphenyl) propionic acid (5.09 g, 25.9 mmol), pivalic acid anhydride (14.3 g, 76.6 mmol), and tetrahydrofuran (64 ml) were added, and thereafter the mixture was bubbled with nitrogen gas for 10 minutes. Palladium acetate (57 mg, 0.254 mmol) and triphenylphosphine (349 mg, 1.33 mmol) were added thereto, and thereafter the mixture was bubbled with nitrogen gas for 20 minutes to substitute nitrogen gas completely for the gas in the system of reaction, whereby the system was filled with nitrogen gas. Next, hydrogen gas was added thereinto to substitute hydrogen gas for the gas in the system, and then the mixture was stirred under hydrogen pressure of 5.4 MPa at 80° C. for 24 hours for reaction. Thus obtained reaction solution was concentrated under reduced pressure to remove tetrahydrofuran by vaporization. The remaining residue was subjected to a purification process with a silica gel column chromatography (eluting solvent: hexane/ethyl acetate=2/1). The thus eluted fractions containing the object compound were concentrated under reduced pressure to obtain crude 3-(3-hydroxy-4-methoxyphenyl) propionaldehyde (2.26 g, 12.5 mmol, yield: 48%) in the slightly yellow coloured solid.
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:10])[C@@H:4]2[O:9][CH2:8][C@H:6]([CH:7]=1)[O:5]2.[CH2:11](O)[CH2:12][OH:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OCC)(=O)C>C1C=CC=CC=1>[CH2:12]1[O:13][C:3]2([C:2]([Br:1])=[CH:7][C@H:6]3[CH2:8][O:9][C@@H:4]2[O:5]3)[O:10][CH2:11]1
Reactant: OCCO
Reactant: O=C1C(Br)=C[C@H]2CO[C@@H]1O2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: BrC1=C[C@H]2CO[C@H](O2)C12OCCO2
Temperature: 25 °C
Yield: 74.8 %

Procedure:
22 g of 1,6-anhydro-3-bromo-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose was dissolved in 500 ml of dry benzene, and 66 g of ethylene glycol and 3 g of p-toluenesulfonic acid monohydrate were added thereto. The mixture was refluxed under heating while removing formed water. 19 hours later, disappearance of the starting material was confirmed by TLC, and the reaction mixture was cooled to room temperature. Then, 500 ml of ethyl acetate was added thereto, and the mixture was washed three times with 200 ml of a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained crude crystals were purified by silica gel column chromatography (ethyl acetate: hexane=1:1) to obtain 20 g of 1,6-anhydro-3-bromo-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose ethylene acetal as white crystals. The NMR analytical data of this product are as follows.