Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C.C(P(CCCC)CCCC)CCC.[Cl:30][C:31]1[C:39]([F:40])=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][CH2:34][N:35]2[C@@H:41]([CH2:60][CH2:61]O)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([S:51](=[O:59])(=[O:58])[NH:52][C:53]2[S:54][CH:55]=[CH:56][N:57]=2)=[CH:47][N:46]=1)=[O:43].O>C1COCC1>[Cl:30][C:31]1[C:39]([F:40])=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][CH2:34][N:35]2[C@H:41]1[CH2:60][CH2:61][N:44]([C:45]2[N:46]=[CH:47][C:48]([S:51]([NH:52][C:53]3[S:54][CH:55]=[CH:56][N:57]=3)(=[O:59])=[O:58])=[CH:49][CH:50]=2)[C:42]1=[O:43]
Reactant: O=C(Nc1ccc(S(=O)(=O)Nc2nccs2)cn1)[C@H](CCO)N1CCc2c1ccc(F)c2Cl
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: CCCCP(CCCC)CCCC
Solvent: C1CCOC1
Solvent: O
Product: O=C1[C@@H](N2CCc3c2ccc(F)c3Cl)CCN1c1ccc(S(=O)(=O)Nc2nccs2)cn1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
Prepared using General Procedure 3. To a stirring solution of di-tert-butyl-azodicarboxylate (44 mg, 0.05 mmol) and THF (0.5 mL), under N2, at 0° C., was added tributylphosphine (48 mg, 0.19 mmol), dropwise over 5 minutes. The colourless solution was stirred at 0° C. for 30 minutes. A solution of (S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide (24 mg, 0.05 mmol) in THF (0.5 mL) was added dropwise over 5 minutes. The solution was stirred at ambient temperature for 2 hours. To this solution was added H2O (40 uL) and the solution was evaporated to dryness. The residue was purified via reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) gave (S)-6-(3-(4-chloro-5-fluoroindolin-1-yl)-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)pyridine-3-sulfonamide. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=494.1; tR=1.69 min. 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.43 (d, J=8.8 Hz, 1H), 8.20 (dd, J=8.9, 2.5 Hz, 1H), 7.30 (d, J=4.6 Hz, 1H), 7.01 (t, J=9.2 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 6.48 (dd, J=8.7, 3.6 Hz, 1H), 4.89 (q, J=6.6 Hz, 1H), 4.18 (t, J=9.7 Hz, 1H), 3.84-3.77 (m, 1H), 3.65-3.59 (m, 1H), 3.39-3.37 (m, 1H), 3.05-2.98 (m, 2H), 2.38-2.31 (m, 1H), 2.21-2.10 (m, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([C:12]([O:14]C)=[O:13])[CH:11]=1)[NH:8][CH2:7][CH2:6][CH2:5]2.[CH3:16][S:17](Cl)(=[O:19])=[O:18]>>[CH3:16][S:17]([NH:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([C:12]([OH:14])=[O:13])[CH:11]=1)[NH:8][CH2:7][CH2:6][CH2:5]2)(=[O:19])=[O:18]
Reactant: COC(=O)c1cc(N)cc2c1NCCC2
Reactant: CS(=O)(=O)Cl
Product: CS(=O)(=O)Nc1cc2c(c(C(=O)O)c1)NCCC2
Yield: 79.9 %

Procedure:
The title compound was prepared (79.9% yield) from methyl 6-amino-1,2,3,4-tetrahydroquinoline-8-carboxylate by the same procedure as in Example 32 by using methanesulfonyl chloride instead of p-toluenesulfonyl chloride. This compound was recrystallized form ethanol to give yellow crystals, mp 244° C.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:2].[Br:9][C:10]1[CH:11]=[C:12]([SH:19])[C:13](=[CH:17][CH:18]=1)[C:14](O)=[O:15]>N1C=CC=CC=1>[Br:9][C:10]1[CH:18]=[CH:17][C:13]2[C:14](=[O:15])[N:2]=[C:1]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=3)[S:19][C:12]=2[CH:11]=1
Reactant: N#Cc1ccccn1
Reactant: O=C(O)c1ccc(Br)cc1S
Solvent: c1ccncc1
Product: O=c1nc(-c2ccccn2)sc2cc(Br)ccc12
Yield: 36.9 %

Procedure:
2-Cyanopyridine (0.29 g, 2.8 mmol) and 4-bromothiosalicylic acid (0.8 g, 3.4 mmol) were dissolved in pyridine (6 ml), and the mixture was refluxed for 8 hrs. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. The fractions eluted with chloroform-ethyl acetate (5:1, v/v) were collected, concentrated and recrystallized from hexane-chloroform to give the titled compound (0.33 g, 36%) as white crystals.
Reaction SMILES: C([O:3][C:4](=[O:26])[C:5]([CH3:25])([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)C.[C:27]1([C:33]2[O:34][C:35]([CH3:51])=[C:36]([CH2:38][CH2:39]OS(C3C=CC(C)=CC=3)(=O)=O)[N:37]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[CH3:25][C:5]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=1)([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:39][CH2:38][C:36]2[N:37]=[C:33]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:34][C:35]=2[CH3:51])=[CH:11][CH:12]=1)[C:4]([OH:3])=[O:26]
Reactant: CCOC(=O)C(C)(Cc1ccc(O)cc1)Oc1cccc(C(F)(F)F)c1
Reactant: Cc1ccc(S(=O)(=O)OCCc2nc(-c3ccccc3)oc2C)cc1
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(CC(C)(Oc2cccc(C(F)(F)F)c2)C(=O)O)cc1

Procedure:
Standard Procedure (B) was utilized to prepare the title compound from 3-(4-hydroxy-phenyl)-2-methyl-2-(3-trifluoromethyl-phenoxy)-propionic acid ethyl ester and toluene-4-sulfonic acid 2-(2-phenyl-5-methyl-oxazol-4-yl)-ethyl ester. 1H NMR (400 MHz, CDCl3) δ 7.99-7.97 (m, 2H), 7.50-7.46 (m, 3H), 7.33 (t, 1H, J=8.21 Hz), 7.26-7.24 (m, 1H), 7.17 (d, 2H, J=8.60 Hz), 7.14-7.12 (m, 1H), 7.04-7.01 (m, 1H), 6.81 (d, 2H, J=8.60 Hz), 4.20 (t, 2H, J=5.87 Hz), 3.27 (d, 1H, J=14.08 Hz), 3.14 (d, 1H, J=14.08 Hz), 3.07 (t, 2H, J=5.87 Hz), 2.42 (s, 3H), 1.44 (s, 3H); HRMS (ES+) m/z exact mass calcd for C29H27NO5F3 526.1841, found 526.1845.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)[N:5]=[CH:4][C:3]=1[C:12]([NH2:14])=[O:13].[CH2:15]([N:22]1[CH2:26][CH2:25][CH:24]([C:27](OC)=O)[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH2:15]([N:22]1[CH2:26][CH2:25][CH:24]([C:27]2[NH:14][C:12](=[O:13])[C:3]3[CH:4]=[N:5][N:6]([CH:7]4[CH2:11][CH2:10][CH2:9][CH2:8]4)[C:2]=3[N:1]=2)[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: COC(=O)C1CCN(Cc2ccccc2)C1
Reactant: NC(=O)c1cnn(C2CCCC2)c1N
Product: O=c1[nH]c(C2CCN(Cc3ccccc3)C2)nc2c1cnn2C1CCCC1

Procedure:
Following the procedure for the preparation of 6-[(3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl]-1-(2-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one but substituting 5-amino-1-cyclopentyl-1H-pyrazole-4-carboxamide and methyl 1-benzylpyrrolidine-3-carboxylate provided the title compound. 400 MHz 1H NMR (CDCl3) δ 8.01 (s, 1H), 7.39-7.32 (m, 4H), 7.27-7.23 (m, 1H), 5.12-5.09 (m, 1H), 3.84 (d, J=12.4 Hz, 1H), 3.61 (d, J=12.4 Hz, 1H), 3.30-3.26 (m, 1H), 3.18-3.14 (m, 1H), 3.01 (d, J=9.9 Hz, 1H), 2.45-2.32 (m, 3H), 2.11-1.90 (m, 7H), 1.71-1.65 (m, 2H). MS: (M+H m/z=364.1).
Reaction SMILES: [OH:1][NH:2][C:3](=[NH:7])[CH:4]([CH3:6])[CH3:5].[C:8]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH:35]2[CH2:37][CH2:36]2)[C:17](=[O:34])[C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=3)=[N:20][CH:19]=2)[CH2:12][CH2:11]1)#N>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH:35]1([N:16]([CH:13]2[CH2:14][CH2:15][N:10]([C:8]3[O:1][N:2]=[C:3]([CH:4]([CH3:6])[CH3:5])[N:7]=3)[CH2:11][CH2:12]2)[C:17](=[O:34])[C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:25]=[CH:26][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:28][CH:29]=3)=[N:20][CH:19]=2)[CH2:37][CH2:36]1
Reactant: CS(=O)(=O)c1ccc(-c2ccc(C(=O)N(C3CC3)C3CCN(C#N)CC3)cn2)cc1
Reactant: CC(C)C(=N)NO
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)c1noc(N2CCC(N(C(=O)c3ccc(-c4ccc(S(C)(=O)=O)cc4)nc3)C3CC3)CC2)n1
Temperature: 50 °C
Reaction time: 48 h

Procedure:
0.5 M solution of zinc chloride in tetrahydrofuran (4.52 mL) is added dropwise at room temperature to a mixture of N-hydroxy-isobutyramidine (58 mg) and N-(1-cyano-piperidin-4-yl)-N-cyclopropyl-6-(4-methanesulfonyl-phenyl)-nicotinamide (160 mg) in ethyl acetate (8 mL). The reaction mixture is stirred at 50° C. for two days and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 1 h in a mixture of ethanol (6 mL) and glacial acetic acid (3 mL). The solvents are evaporated in vacuo and dichloromethane and 10% aqueous K2CO3 solution are added to the residue. The organic phase is separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is triturated with diethyl ether to give the title compound. LC (method 8): tR=1.51 min; Mass spectrum (ESI+): m/z=510 [M+H]+.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.C[O:27][C:28]([C@@H:30]1[CH2:34][C@H:33]([N:35]2[CH:39]=[C:38](I)[CH:37]=[N:36]2)[CH2:32][N:31]1C(OCC1C=CC=CC=1)=O)=[O:29].[F-].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:25][C:11]1[N:12]=[CH:13][C:14]([C:38]2[CH:37]=[N:36][N:35]([C@@H:33]3[CH2:32][NH:31][C@H:30]([C:28]([OH:29])=[O:27])[CH2:34]3)[CH:39]=2)=[CH:15][C:10]=1[C:2]1[S:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1
Reactant: COC(=O)[C@@H]1C[C@H](n2cc(I)cn2)CN1C(=O)OCc1ccccc1
Reactant: CC1(C)OB(c2cnc(N)c(-c3nc4ccccc4s3)c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [F-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: Nc1ncc(-c2cnn([C@@H]3CN[C@H](C(=O)O)C3)c2)cc1-c1nc2ccccc2s1
Temperature: 60 °C

Procedure:
A mixture of 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (BB8) (200 mg, 0.566 mmol), (2S,4S)-4-(4-iodopyrazol-1-yl)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (309.0 mg, 0.679 mmol), Pd(PPh3)4 (60 mg, 0.06 mmol), potassium fluoride (98.7 mg, 1.70 mmol), and 4:1 dioxane:water (5 mL) was heated in the microwave reactor at 85° C. for 30 min. The material was concentrated in vacuo, then dry-loaded onto silica gel for column chromatography. The product was eluted with 2→5% MeOH/DCM, and the fractions containing the product were concentrated in vacuo. The material was dissolved in conc. HCl, transferred to a sealed tube and heated at 60° C. for 2 h. The solvent was removed using the corrosive pump to afford the title compound as a brown solid. 1H NMR (400 MHz, CD3OD): δ=2.73 (ddd, J=14.0, 6.5, 4.5 Hz, 1H), 3.07 (ddd, J=14.1, 10.0, 7.5 Hz, 1H), 3.81-3.93 (m, 2H), 4.68 (dd, J=10.0, 6.7 Hz, 1H), 5.36 (ddd, J=6.8, 3.8, 3.5 Hz, 1H), 7.56-7.63 (m, 2H), 8.05 (s, 1H), 8.08-8.11 (m, 1H), 8.16 (d, J=7.6 Hz, 1H), 8.32-8.36 (m, 2H), 8.72 (d, J=2.0 Hz, 1H). MS (ES′): m/z=407.13 (100) [MH+]. HPLC: tR=2.28 min (ZQ2, polar—5 min).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[O:17][CH:9]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:16].[NH:18]1[CH:22]=[CH:21][N:20]=[CH:19]1>O>[OH:17][CH:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])[CH:9]([N:18]1[CH:22]=[CH:21][N:20]=[CH:19]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:16]
Reactant: Clc1ccccc1C1OC1c1ccccc1Cl
Reactant: c1c[nH]cn1
Solvent: O
Product: OC(c1ccccc1Cl)C(c1ccccc1Cl)n1ccnc1
Yield: 86.8 %

Procedure:
A mixture of 11 g (0.04 m) of 2,2'-dichloro-α,α'-epoxybibenzyl and 15 g (0.22 m) of imidazole is heated at 160° for 11/2 hours. The reaction is cooled, diluted with water, and extracted with ether. The combined ether extracts are washed with water, then saturated sodium chloride solution, and dried over MgSO4. Solvent is evaporated to give 12 g of a gummy solid, mp 62°-68°.
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:35])=[C:7]2[C:12](=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[N:14]=1)[N:11]([CH2:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[C:10](=[O:28])[C:9]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:8]2)=[O:4].[NH2:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH:22]1([CH2:21][N:11]2[C:12]3[C:7](=[C:6]([OH:35])[C:5]([C:3]([NH:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[O:4])=[N:14][C:13]=3[C:15]3[CH:16]=[CH:17][N:18]=[CH:19][CH:20]=3)[CH:8]=[C:9]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:10]2=[O:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: COC(=O)c1nc(-c2ccncc2)c2c(cc(-c3ccccc3)c(=O)n2CC2CCCCC2)c1O
Reactant: NCCC(=O)O
Agent: C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: O=C(O)CCNC(=O)c1nc(-c2ccncc2)c2c(cc(-c3ccccc3)c(=O)n2CC2CCCCC2)c1O
Temperature: 25 °C
Yield: 9.7 %

Procedure:
A mixture of 1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (46 mg, 0.098 mmol), β-alanine (699 mg, 7.8 mmol) and NaOMe solution (11.8 mL, 5.9 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-100% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4, and the resulting precipitate was isolated by filtration to give 5 mg of the title compound. MS: (+) m/z 527.45 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([CH:9]3[CH2:12][C:11](=O)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:16][C@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1.N1C=CC=CC=1.B>ClCCl.C(O)C>[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@@H:11]([N:18]4[CH2:19][CH2:20][CH2:21][C@@H:17]4[CH3:16])[CH2:10]3)[S:8][C:4]=2[CH:3]=1
Reactant: C[C@H]1CCCN1
Reactant: O=C1CC(c2nc3ccc(Br)cc3s2)C1
Agent: B
Solvent: CCO
Solvent: c1ccncc1
Solvent: ClCCl
Product: C[C@H]1CCCN1[C@H]1C[C@@H](c2nc3ccc(Br)cc3s2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 15.8 %

Procedure:
The product of Example 1C (500 mg, 1.77 mmole) was dissolved in 6 ml dichloromethane and 4 ml ethanol. 2-(S)-methylpyrrolidine (1.04 g, 4.43 mmole, toluene extract from 50% sodium hydroxide) was then added and the solution was stirred at room temperature for 30 minutes. Borane-pyridine (358 μl, 3.54 mmole) was added, and the mixture was stirred at room temperature overnight. The reaction was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the crude product which was purified by column chromatography (0.4% ammonium hydroxide and 4% methanol in dichloromethane) to give 98 mg (16% yield) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 7.98 (d, J=2.14 Hz, 1H) 7.80 (d, J=8.85 Hz, 1H) 7.54 (dd, J=8.54, 1.83 Hz, 1H) 3.54-3.65 (m, 1H) 3.15-3.29 (m, 1H) 3.00-3.12 (m, 1H) 2.74-2.85 (m, 1H) 2.58-2.68 (m, 1H) 2.43-2.56 (m, 3H) 2.30-2.39 (m, 1H) 1.92-2.02 (m, 1H) 1.78-1.89 (m, 1H) 1.70-1.76 (m, 1H) 1.44-1.59 (m, 1H) 1.16 (s, 3H). MS: (M+H)+=351/353.
Reaction SMILES: I([O-])(=O)(=O)=[O:2].[Na+].[F:7][C:8]([F:46])([F:45])[C:9]1[CH:10]=[C:11]([C:19]([CH3:44])([CH3:43])[C:20]([N:22]([CH3:42])[C:23]2[CH:24]=[N:25][C:26]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:27][C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])=[O:21])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1>C(Cl)(Cl)(Cl)Cl.O.O.[Ru](=O)=O>[F:46][C:8]([F:7])([F:45])[C:9]1[CH:10]=[C:11]([C:19]([CH3:44])([CH3:43])[C:20]([N:22]([CH3:42])[C:23]2[CH:24]=[N:25][C:26]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][C:37]3=[O:2])=[CH:27][C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])=[O:21])[CH:12]=[C:13]([C:15]([F:18])([F:16])[F:17])[CH:14]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: Cc1ccccc1-c1cc(N2CCOCC2)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: O=[Ru]=O
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: Cc1ccccc1-c1cc(N2CCOCC2=O)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 34.3 %

Procedure:
To an ice-cooled suspension of 1.2 g (7.1 mmol) ruthenium(IV)oxide hydrate in a mixture of 50 ml carbon tetrachloride and 50 ml water were added 9.0 g (42 mmol) sodium periodate. After stirring for 30 min the organic layer was separated and the aqueous layer was extracted twice with 10-ml portions of carbon tetrachloride. The combined organic layers were filtered over celite, cooled to 0° C. and were added slowly to an ice-cooled solution of 2.0 g (3.54 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide in 20 ml carbon tetrachloride. The mixture was stirred for additional 15 min at 0° C., was filtered over celite and was evaporated. The residue was purified by flash-chromatography and gave 704 mg (34%) of the title compound as colourless foam. MS m/e (%): 580 (M+H+, 100).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:12][C:13](=O)[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=3)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:13]1[C:14]2[C:19](=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=2)[CH:20]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=2)[N:12]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc2c(=O)[nH]c(-c3ccc(OC(C)C)cc3)cc2c1
Product: COc1ccc2c(Cl)nc(-c3ccc(OC(C)C)cc3)cc2c1
Yield: 67.4 %

Procedure:
A solution of 3-(4-isopropoxyphenyl)-6-methoxyisoquinolin-1(2H)-one (3.5 g, 11.31 mmol) in POCl3 (11 ml) was refluxed for overnight. The solvent was evaporated under reduced pressure and the residue was diluted with cold water. The aqueous solution was basified by solid sodium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (10% ethyl acetate in pet ether) to get desired compound (2.5 g, 67.4%) as pale yellow solid. 1H NMR (400 MHz, CDCl3): δ ppm 8.06-8.04 (d, J=8 Hz, 1H), 8.03-8.01 (d, J=8 Hz, 2H), 7.81 (s, 1H), 7.22-7.20 (d, J=8 Hz, 1H), 7.00 (s, 1H), 6.99-6.97 (d, J=8 Hz, 1H), 4.63 (m, 1H), 3.96 (s, 3H), 1.38 (m, 6H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:13]=[CH:12]2.[CH2:24]([NH:26][CH2:27][CH3:28])[CH3:25]>>[CH2:24]([N:26]([CH2:27][CH3:28])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:13]=[CH:12]2)[CH3:25]
Reactant: BrCCCCCCOc1ccc2c(ccn2-c2ccccc2)c1
Reactant: CCNCC
Product: CCN(CC)CCCCCCOc1ccc2c(ccn2-c2ccccc2)c1

Procedure:
In analogy to example 4.4, 5-(6-Bromo-hexyloxy)-1-phenyl-1H-indole and diethylamine were converted to yield Diethyl-[6-(1-phenyl-1H-indol-5-yloxy)-hexyl]-amine as colorless oil, MS: 365 (MH+).
Reaction SMILES: [CH:1]([NH:4][N:5]=[C:6]([CH2:8][CH3:9])[CH3:7])([CH3:3])[CH3:2].Cl[O-:11].[Na+]>>[CH:1]([N:4]=[N:5][C:6]([OH:11])([CH2:8][CH3:9])[CH3:7])([CH3:3])[CH3:2]
Reactant: CCC(C)=NNC(C)C
Reactant: [O-]Cl
Agent: [Na+]
Product: CCC(C)(O)N=NC(C)C
Reaction time: 3 h

Procedure:
Into a 250 ml 4-neck round bottom flask equipped with a reflux condenser, thermometer, graduated addition funnel and a magnetic stirrer was added 18.1 grams (0.14 moles) of methyl ethyl ketone isopropyl-hydrazone. With efficient stirring 170 mls of 12.4% by wt. aqueous sodium hypochlorite was added dropwise while holding the reaction temperature at 25°-30° C with a water bath. The oxidation was monitored by gas chromatography and after 3 hours stirring the hydrazone was completely oxidized. The reaction mixture was transferred to a separatory funnel and the spent aqueous hypochlorite solution separated. The organic layer was washed with 40 ml of cold 15% sodium bisulfite solution and then 25 ml of sodium bicarbonate solution. The organic layer was taken up in 50 ml of pentane, dried over anhydrous sodium sulfate, filtered and the pentane evaporated on a rotating evaporator under reduced pressure at 10°-20° C. The residue was an orange-yellow liquid weighing 9.4 grams (46.5% crude yield). The infrared spectrum of the product was similar to the infrared spectrum of 2-isopropylazo-2-hydroxybutane prepared by the α-chloro route (Example 5-a-2).
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][NH:10][C:11]1[C:12]2[N:13]([C:21](=[O:24])[NH:22][N:23]=2)[CH:14]=[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[N:16]=1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[NH2:7][CH2:8][CH2:9][NH:10][C:11]1[C:12]2[N:13]([C:21](=[O:24])[NH:22][N:23]=2)[CH:14]=[C:15]([C:17]([CH3:18])([CH3:19])[CH3:20])[N:16]=1
Reactant: CC(C)(C)OC(=O)NCCNc1nc(C(C)(C)C)cn2c(=O)[nH]nc12
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)c1cn2c(=O)[nH]nc2c(NCCN)n1

Procedure:
A solution of 100 mg of [2-(6-tert-butyl-3-oxo-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-8-ylamino)-ethyl]-carbamic acid tert-butyl ester in dichloromethane (5.0 mL) was treated with 1.48 g of TFA at ambient temperature for 16 h. The solvent was removed and the residue was recrystallized from ether to afford the title compound as a white solid. MS (M+H+)=251.3.
Reaction SMILES: [O:1]1[C:6]2=[CH:7][CH:8]=[CH:9][C:5]2=[CH:4][C:3](C(CC)C#N)=[CH:2]1.[OH-].[NH4+:16]>[Rh].C(O)C>[O:1]1[C:6]2=[CH:7][CH:8]=[CH:9][C:5]2=[CH:4][C:3]([NH:16][CH2:2][CH2:3][CH2:4][CH3:5])=[CH:2]1
Reactant: CCC(C#N)c1coc2cccc-2c1
Reactant: [NH4+]
Agent: [Rh]
Agent: [OH-]
Solvent: CCO
Product: CCCCNc1coc2cccc-2c1
Yield: 72 %

Procedure:
This compound was prepared by the same method as for intermediate 30, using 4-benzofuran-3-yl-butyronitrile (1.05 g, 5.67 mmol), 420 mg of 5% rhodium on alumina, 100 mL of ammonium hydroxide, and 150 mL of ethanol, to afford 770 mg (72%) of the title compound after chromatography: 1H NMR (CDCl3, 400 MHz) δ 7.52 (d, J=8.2 Hz, 1 H), 7.43 (d, J=8.1 Hz, 1 H), 7.38 (s, 1 H), 7.18-7.27 (m, 2 H), 2.72 (t, J=7.0 Hz, 2 H), 2.67 (t, J=7.3 Hz, 2 H), 1.73 (quint, J=7.9 Hz, 2 H).