Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN(C(C)C)C(C)C.[F:10][C:11]([F:28])([F:27])[O:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[C:19]([C:24]([OH:26])=O)=[CH:18]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:53]1[C:58]2[CH:59]=[CH:60][C:61]([C:63]3[CH:64]=[C:65]([NH2:69])[CH:66]=[CH:67][CH:68]=3)=[CH:62][C:57]=2[O:56][CH2:55][CH2:54]1>CN(C=O)C>[O:53]1[C:58]2[CH:59]=[CH:60][C:61]([C:63]3[CH:64]=[C:65]([NH:69][C:24]([C:19]4[C:20](=[O:23])[O:21][C:22]5[C:17]([CH:18]=4)=[CH:16][CH:15]=[CH:14][C:13]=5[O:12][C:11]([F:10])([F:28])[F:27])=[O:26])[CH:66]=[CH:67][CH:68]=3)=[CH:62][C:57]=2[O:56][CH2:55][CH2:54]1
Reactant: Nc1cccc(-c2ccc3c(c2)OCCO3)c1
Reactant: O=C(O)c1cc2cccc(OC(F)(F)F)c2oc1=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1cccc(-c2ccc3c(c2)OCCO3)c1)c1cc2cccc(OC(F)(F)F)c2oc1=O
Temperature: 25 °C
Yield: 67.9 %

Procedure:
DIEA (0.013 mL, 0.072 mmol) was added to 8-trifluoromethoxy-3-carboxy-coumarin (0.020 g, 0.067 mmol) and HATU (0.028 g, 0.072 mmol) in 0.36 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-phenylamine (0.015 g, 0.067 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.022 g of product in 67% yield: LCMS (ESI) m/z 484 (MH+).
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.C(N(CC)CC)C.[CH:21]1[N:25]=[CH:24][N:23]([C:26](N2C=NC=C2)=[O:27])[CH:22]=1>C1COCC1.CCOC(C)=O>[N:23]1([C:26]([O:1][C@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[O:27])[CH:22]=[CH:21][N:25]=[CH:24]1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CC(C)(C)OC(=O)N1CC[C@H](O)C1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CC[C@H](OC(=O)n2ccnc2)C1
Temperature: 50 °C
Yield: 64.5 %

Procedure:
To a solution of tert-butyl (3S)-3-hydroxypyrrolidine-1-carboxylate (360 mg, 1.9 mmol) in THF (8 mL) was added triethylamine (253 mg, 349 μL, 2.5 mmol) followed by the addition of CDI (374 mg, 2.3 mmol) portionwise. The reaction mixture was heated at 50° C. for 3 h, cooled to room temperature and diluted with EtOAc. The organic layer was washed with 1 M HCl solution, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via silica gel column chromatography using 20 to 100% EtOAc in hexanes to obtain (S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl 1H-imidazole-1-carboxylate (345 mg, 64%). 1HNMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.42 (d, J=1.2 Hz, 1H), 7.09 (s, 1H), 4.46 (s, 1H), 3.66 (dd, J=33.8, 10.7 Hz, 1H), 3.56-3.29 (m, 2H), 2.25 (s, 1H), 2.04-1.87 (m, 2H), 1.48 (t, J=4.0 Hz, 9H). LC/MS m/z 282.4 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]#[C:9][C:10]1[S:23][C:13]2[C:14]3[CH:22]=[N:21][CH:20]=[CH:19][C:15]=3[O:16][CH2:17][CH2:18][C:12]=2[CH:11]=1.[N-:24]=[N+:25]=[N-:26].[Na+].O>CS(C)=O>[S:23]1[C:13]2[C:14]3[CH:22]=[N:21][CH:20]=[CH:19][C:15]=3[O:16][CH2:17][CH2:18][C:12]=2[CH:11]=[C:10]1[C:9]1[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[N:26][NH:25][N:24]=1
Reactant: [N-]=[N+]=[N-]
Reactant: Clc1ccccc1C#Cc1cc2c(s1)-c1cnccc1OCC2
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: Clc1ccccc1-c1n[nH]nc1-c1cc2c(s1)-c1cnccc1OCC2
Temperature: 90 °C
Yield: 18.4 %

Procedure:
A mixture of 68 mg (0.2 mmol) of 2-((2-chlorophenyl)ethynyl)-4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepine and 52 mg (0.8 mmol) of sodium azide in 4 ml of dimethylsulfoxide was heated at 90° C. for 36 hours. Water (20 ml) was added to the mixture and extracted 6 times with 10 ml of ethyl acetate. The combined organic extracts were washed with water, brine and dried over sodium sulfate. The solvent was removed in vacuum and the crude product was recrystallized from ethyl acetate to give 324 (14 mg, 18%). 1H NMR (400 MHz, DMSO) δ 8.68 (s, 1H), 8.24 (d, J=5.5, 1H), 7.73-7.46 (m, 4H), 6.98 (d, J=5.5, 1H), 6.77 (s, 1H), 4.31 (t, J=4.7, 2H), 3.08 (t, J=4.7, 2H). MS: (ESI+) 381.1
Reaction SMILES: [C:1]([C:8]1C=CC(C(O)=O)=[C:10]([NH:17]N)[CH:9]=1)([O:3]C(C)(C)C)=O.[NH:19]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[NH2:20].C(N(CC)CC)C.CC([O:41]C(ON=C(C1C=CC=CC=1)C#N)=O)(C)C.[ClH:55]>CN(C)C=O>[ClH:55].[ClH:55].[NH:19]([C:21]1[CH:22]=[CH:23][C:24]([C:25]([O:27][N:17]2[C:1](=[O:3])[CH2:8][CH2:9][C:10]2=[O:41])=[O:26])=[CH:28][CH:29]=1)[NH2:20]
Reactant: CC(C)(C)OC(=O)c1ccc(C(=O)O)c(NN)c1
Reactant: CC(C)(C)OC(=O)ON=C(C#N)c1ccccc1
Reactant: NNc1ccc(C(=O)O)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: NNc1ccc(C(=O)ON2C(=O)CCC2=O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 69 %

Procedure:
Synthesis of 4-BOC-hydrazinobenzoic acid--To a stirred solution of 4-hydrazinobenzoic acid (1 equivalent) and triethylamine (3 equivalents) in dimethylformamide (5 mg/1) was added dropwise a solution of BOC-ON (1 equivalent) in dimethylformamide. The reaction mixture was stirred at room temperature for 3 hours. Ten percent aqueous hydrochloric acid was added and subsequently the solution became cloudy. The solution was extracted with ethyl acetate and the combined organic extracts were washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a brown solid. The solid was recrystallized from chloroform to give the desired product as a pale brown solid; yield 69%. Analysis:
Reaction SMILES: [CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[N:16]([C:17]4[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=4)[N:15]=[CH:14][CH:13]=3)=[CH:9][CH:10]=2)[NH:5][N:4]=1)[CH3:2].Br[CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C.O>[CH2:1]([C:3]1[N:4]([CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[N:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][C:8]([C:12]1[N:16]([C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[N:15]=[CH:14][CH:13]=1)=[CH:7]2)[CH3:2]
Reactant: CCc1n[nH]c2cc(-c3ccnn3-c3ccc(S(C)(=O)=O)cc3)ccc12
Reactant: CCC(Br)CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCc1c2ccc(-c3ccnn3-c3ccc(S(C)(=O)=O)cc3)cc2nn1C(CC)CC
Temperature: 60 °C
Reaction time: 48 h
Yield: 3.7 %

Procedure:
3-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole (100 mg, 0.27 mmol), 3-bromopentane (70 mg, 0.46 mmol), potassium carbonate (45 mg, 0.33 mmol) and N,N-dimethylformamide (2 mL) were added to a 1-necked flask. The mixture was heated to 60° C. for 6 hours, then slowly cooled to room temperature and stirred for a further 48 hours. A further equivalent of 3-bromopentane (41 mg, 0.27 mmol) was then added, and the reaction was heated to 120° C. After cooling to room temperature, water and ethyl acetate were added. The product was extracted once with ethyl acetate, and washed with water and brine. The combined organics were dried, and filtered and concentrated. The reside was purified by column chromatography on silica gel (eluting using 50% ethyl acetate in hexanes for 10 minutes and then a linear gradient to 100% ethyl acetate in hexanes at 20 minutes) to give 4.4 mg (3.7%) of 3-ethyl-2-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-2H-indazole. LC/MS (EI) tR 4.36 (Method C), m/z 437.1 (M++1), 1H NMR (CDCl3) δ 0.6 (t, 3H), 1.4 (t, 2H), 1.8 (m, 2H), 1.9 (m, 2H), 3.0 (m, 6H), 4.0 (m, 1H), 6.5 (s, 1H), 7.0 (d, 1H), 7.1 (s, 1H), 7.5 (d, 2H), 7.7 (m, 1H), 7.8 (s, 1H), 7.8 (d, 2H). 13 mg (11%) of the corresponding isomer (3-ethyl-1-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole) was also isolated.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:11]=[C:12]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[C:13]4[S:18][CH:17]=[CH:16][C:14]=4[N:15]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([BH3-])#N.[Na+].[C:29](O)(=[O:31])[CH3:30]>>[O:22]1[CH2:21][CH2:20][N:19]([C:12]2[C:13]3[S:18][CH:17]=[CH:16][C:14]=3[N:15]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[C:9]4[C:4]=3[CH2:3][CH2:2][N:1]4[C:29](=[O:31])[CH3:30])[N:11]=2)[CH2:24][CH2:23]1
Reactant: CC(=O)O
Reactant: c1cc(-c2nc(N3CCOCC3)c3sccc3n2)c2cc[nH]c2c1
Agent: [BH3-]C#N
Agent: [Na+]
Product: CC(=O)N1CCc2c(-c3nc(N4CCOCC4)c4sccc4n3)cccc21
Temperature: 60 °C

Procedure:
To a solution of 2-(1H-Indol-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine 199 (100 mg) in acetic acid (2 ml) was added sodium cyanoborohydride (76 mg) and the reaction mixture was heated at 60° C. overnight. The mixture was then basified and extracted into dichloromethane, organic layer was dried (Mg2SO4), filtered and volatiles removed in vacuo. Flash chromatography and recrystallization from hot dichloromethane/hexane gave 228 (11 mg). NMR: (DMSO-d6): 2.21 (3H, s), 3.70 (2H, t, J=8.6), 3.80-3.86 (4H, m), 3.98-4.04 (4H, m), 4.17 (2H, t, J=8.5), 7.30 (1H, t, J=7.9), 7.55 (1H, d, J=5.6), 8.00 (1H, d, J=8.4), 8.25 (1H, d, J=7.8), 8.30 (1H, d, J=5.6) MS: (ESI+): 381
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].I[C:14]1[C:22]2[C:17](=[N:18][CH:19]=[N:20][C:21]=2[NH2:23])[N:16]([CH:24]([CH3:26])[CH3:25])[N:15]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.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>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([CH:24]([CH3:26])[CH3:25])[N:15]=[C:14]([C:7]3[CH:8]=[CH:9][C:4]([C:1](=[O:3])[CH3:2])=[CH:5][CH:6]=3)[C:22]=12
Reactant: CC(=O)c1ccc(B(O)O)cc1
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: COCCOC
Product: CC(=O)c1ccc(-c2nn(C(C)C)c3ncnc(N)c23)cc1
Temperature: 80 °C
Yield: 62.4 %

Procedure:
A solution of 4-Acetylphenylboronic acid (12.7 mg, 0.08 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (20 mg, 0.07 mmol) in DME (12 ml). Pd(PPh3)4 (16 mg, 0.014 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA31 (12.9 mg, 62% yield).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[CH3:22][O:23][CH2:24][C:25](Cl)=[O:26]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:25](=[O:26])[CH2:24][O:23][CH3:22])=[CH:13][CH:14]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(N)cc1
Reactant: COCC(=O)Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: COCC(=O)Nc1ccc(NC(=O)OC(C)(C)C)cc1
Reaction time: 1 h
Yield: 104 %

Procedure:
To a stirred solution of N-t-butoxycarbonyl-1,4-phenylene diamine (0.25 g) in dry tetrahydrofuran (20 ml) were added pyridine (0.12 ml) and methoxyacetyl chloride (0.15 g) and the reaction mixture was stirred for 1 hrs. The solution was diluted with ethyl acetate (50 ml), washed with a 3N solution of hydrochloric acid (30 ml) and brine (30 ml), dried and concentrated in vacuum to give the title compound (0.35 g). T.l.c. CH/EA acetate 1/1. Rf=0.33.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([N+:15]([O-:17])=[O:16])=[C:13](F)[CH:12]=[C:11]([F:19])[C:10]=2[F:20])=[C:4]([F:21])[CH:3]=1.[CH3:22][O-:23].[Na+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([N+:15]([O-:17])=[O:16])=[C:13]([O:23][CH3:22])[CH:12]=[C:11]([F:19])[C:10]=2[F:20])=[C:4]([F:21])[CH:3]=1
Reactant: C[O-]
Reactant: O=[N+]([O-])c1c(F)cc(F)c(F)c1Nc1ccc(Br)cc1F
Agent: [Na+]
Product: COc1cc(F)c(F)c(Nc2ccc(Br)cc2F)c1[N+](=O)[O-]
Yield: 81 %

Procedure:
Intermediate I-4a was prepared from (4-bromo-2-fluoro-phenyl)-(2,3,5-trifluoro-6-nitro-phenyl)-amine (25 g, 0.069 mol) and sodium methoxide (18.6 g, 0.344 mol) using procedures analogous to Intermediate (I-3a) above to afford the product (81% yield).
Reaction SMILES: [N:1]([O-:3])=O.[Na+].[O:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14](=[O:23])[CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]=3)=[CH:13][C:8]=2[O:7][CH2:6]1>CC(O)=O.C1COCC1.O>[O:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14](=[O:23])[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]=3)=[N:1][OH:3])=[CH:13][C:8]=2[O:7][CH2:6]1
Reactant: Cc1cccc(CC(=O)c2ccc3c(c2)OCO3)n1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Cc1cccc(C(=NO)C(=O)c2ccc3c(c2)OCO3)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 80.8 %

Procedure:
Sodium nitrite (0.405 g, 5.88 mmol) was added to a solution of 1-benzo[1,3]dioxol-5-yl-2-(6-methyl-pyridin-2-yl)-ethanone (1.0 g, 3.92 mmol; see Example 3B above) in a mixture of HOAc/THF/H2O (6:4:1, 22 mL). The mixture was stirred at 0° C. for 1 hour and then at room temperature for 1 hour. Solvent was removed under reduced pressure. Residue was dissolved in water and NaOH (3N) was added until the pH value was more than 8. The aqueous solution was then extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to give 0.90 g (81%) of 1-Benzo[1,3]dioxol-5-yl-2-(6-methyl-pyridin-2-yl)ethane-1,2-dione 2-oxime as a yellow foam. MS (ESP+) m/z 285.1 (M+1). 1H NMR (300 MHz, CDCl3) δ 7.49 (m, 4H), 7.09 (d, 1H, J=7.5 Hz), 6.81 (d, 1H, J=7.8 Hz), 6.04 (s, 2H), 2.43 (s, 3H).
Reaction SMILES: [C:1]([C:5]1[N:9]=[C:8]([S:10][CH:11]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:22][N:23]([CH3:27])[C:24](Cl)=[O:25]>>[CH3:22][N:23]([CH3:27])[C:24]([N:7]1[C:8]([S:10][CH:11]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[N:9][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6]1)=[O:25]
Reactant: CC(C)(C)c1n[nH]c(SC(NS(C)(=O)=O)NS(C)(=O)=O)n1
Reactant: CN(C)C(=O)Cl
Product: CN(C)C(=O)n1nc(C(C)(C)C)nc1SC(NS(C)(=O)=O)NS(C)(=O)=O

Procedure:
3-t-butyl-5-(dimethylsulfonamidomethylthio)-1H-1,2,4-triazole was reacted with dimethylcarbamoyl chloride by substantially following the procedure of Example 25(b) to afford 1-dimethylcarbamoyl-3-t-butyl-5-(dimethylsulfonamidomethylthio)-1H-1,2,4-triazole, mp 83°-85° C.
Reaction SMILES: CO.[F:3][C:4]1[CH:5]=[C:6]([N+:16]([O-])=O)[CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1>[Ni].O>[F:3][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[NH2:16]
Reactant: O=[N+]([O-])c1ccc(N2CCOCC2)c(F)c1
Agent: [Ni]
Solvent: O
Solvent: CO
Product: Nc1ccc(N2CCOCC2)c(F)c1
Temperature: 47.5 °C
Reaction time: 8 h
Yield: 90.3 %

Procedure:
Methanol (1.35 Lt) and 3-fluoro-4-morpholinyl nitrobenzene (134 gr) are added into autoclave and followed by Raney Nickel (20.5 gr). The system was flushed with nitrogen and hydrogen gas. The pressure of hydrogen was set to 4.0 kg/cm−2. The reaction mixture was stirred at 45-50° C. under H2 pressure for 8 hrs & the reaction followed by TLC until completion. The reaction mixture was filtered through celite and the filtrate is distilled off evaporate solvent completely U/vacuum at <50° C. temperature. Reaction mass is cooled to 25-30° C. To this DM water (400 ml) is added, Stirred for 1 hr at 25-30° C. The solid is filtered to give 105 gr of 3-fluoro-4-morpholinyl aniline.
Reaction SMILES: [OH-].[Na+].O.[F:4][C:5]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:6]=1[CH:7]=O.[CH3:14][C:15]([CH3:17])=[O:16]>>[F:4][C:5]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:6]=1[CH:7]=[CH:14][C:15](=[O:16])[CH3:17]
Reactant: O=Cc1cc(F)ccc1F
Reactant: CC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)C=Cc1cc(F)ccc1F
Reaction time: 0.5 h

Procedure:
A mixture of acetone (45 ml), sodium hydroxide (3.1 g) and water (230 ml) was combined at room temperature with a solution of 2,5-difluorobenzaldehyde (10.0 g) in acetone (10 ml) and stirred at the same temperature for 30 minutes. Acetone was distilled off under reduced pressure and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine and concentrated under reduced pressure to obtain 4-(2,5-difluorophenyl)-3-buten-2-one (13.8 g).
Reaction SMILES: [C:1]([S:5][C:6]([F:14])([F:13])[C:7]([F:12])([F:11])[C:8]([O-:10])=[O:9])([CH3:4])([CH3:3])[CH3:2].[Na+].S(OC)(O[CH3:20])(=O)=O>>[C:1]([S:5][C:6]([F:14])([F:13])[C:7]([F:11])([F:12])[C:8]([O:10][CH3:20])=[O:9])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)SC(F)(F)C(F)(F)C(=O)[O-]
Reactant: COS(=O)(=O)OC
Agent: [Na+]
Product: COC(=O)C(F)(F)C(F)(F)SC(C)(C)C
Reaction time: 8 h
Yield: 42 %

Procedure:
The resulting dark solution, which contained sodium 3-t-butylthiotetrafluoropropionate, was stirred with 69.3 g (0.55 mole) of dimethyl sulfate while the temperature was maintained at 30°. After an initial exothermic reaction subsided, the mixture was stirred overnight and then distilled to give a crude product with bp about 45° (2 mm, 2.6×10-1 kPa). The distillate was washed with 1 liter of water, dried and fractionated to give 52.1 g (42%) of methyl 3-t-butylthiotetrafluoropropionate, bp 55° (2 mm, 2.6×10-1 kPa). IR (neat): 2970 (sat'd CH), 1775 (C=O), 1100-1250 cm-1 (CF). NMR (CCl4): 1H 3.87 (s, 3H, OCH3) and 1.52 ppm (s, 9H, C(CH3)3 ; 19F-86.3 (t, JFF 7.1 Hz, 2F, CF2S) and -117.6 ppm (t, JFF 7.1 Hz, 2F, CF2C=O).
Reaction SMILES: C([O:4][CH:5]1[C:11]2=[N:12][C:13]([CH3:21])=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:15]=[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6]1)(=O)C.C(=O)([O-])[O-].[K+].[K+].O.C(OCC)(=O)C>C(O)C>[OH:4][CH:5]1[C:11]2=[N:12][C:13]([CH3:21])=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:15]=[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: CCOC(=O)c1cc2c(nc1C)C(OC(C)=O)CCCC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)c1cc2c(nc1C)C(O)CCCC2
Reaction time: 24 h
Yield: 79 %

Procedure:
Ethyl 9-acetoxy-2-methyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carboxylate (4.90 g, 16.81 mmol) was dissolved in ethanol (30 ml), and the solution was mixed with potassium carbonate (3.29 g) and stirred at from 0° C. to room temperature for 24 hours. There action solution was mixed with water and ethyl acetate, and the thus precipitated crystals were filtered. The resulting filtrate was extracted with ethyl acetate, and the thus obtained organic layer was washed with water and saturated brine in that order and dried over anhydrous sodium sulfate. By evaporating the solvent under reduced pressure, the title compound (3.31 g, 79.9%) was obtained as pale yellow amorphous.
Reaction SMILES: Br[CH:2]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[OH:22][C:23]([CH3:33])([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:24][CH2:25][NH2:26].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[OH:22][C:23]([CH3:33])([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:24][CH2:25][NH:26][CH:2]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCCCCCC(C)(O)CCN
Reactant: CCOC(=O)C(Br)CCCCCCCOC1CCCCO1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCCCCC(C)(O)CCNC(CCCCCCCOC1CCCCO1)C(=O)OCC
Yield: 40.5 %

Procedure:
Ethyl 2-bromo-9-tetrahydropyranyloxy-nonanoate (2.5 g) and 3-hydroxy-3-methylnonylamine (2.2 g) were refluxed together in dry ethanol (50 ml) containing sodium carbonate (726 mg) overnight. The ethanol was evaporated in vacuo and the residue was partitioned between ether and brine. The ether solution was washed with brine, dried and evaporated in vacuo. The resulting yellow gum was chromatographed on silica gel (100 g) using chloroform as eluant to give ethyl 2-(3'-hydroxy-3'-methyl-n-nonyl)amino-9-tetrahydropyranyloxy-nonanoate (1.27 g) as a colourless gum.
Reaction SMILES: [C:1]([NH:8][CH:9]1[CH2:12][C:11](=C)[CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([O-])([O-])=[O:15].[K+].[K+]>C(Cl)Cl.O.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([NH:8][CH:9]1[CH2:12][C:11](=[O:15])[CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: C=C1CC(NC(=O)OC(C)(C)C)C1
Reactant: O=C([O-])[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1CC(=O)C1
Yield: 177.6 %

Procedure:
To a vigorously stirring solution of N-Boc-3-methylene-cyclobutanamine (9.8 g, 53.5 mmol) in DCM (160 mL) and H2O (160 mL) was added K2CO3 (3 g, 21.7 mmol), followed by NaIO4 (35 g, 163.5 mmol), tetrabutylammonium chloride (0.2 g, 0.72 mmol) and RuCl3 (0.6 g, 7.6 mmol). During the course of the reaction, the organic solution turned dark brown, the catalyst turned black, while the upper aqueous layer turned white. The reaction was monitored by TLC, and upon completion, the reaction mixture was filtered through a pad of celite. The filtrates were transferred to a separatory funnel, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with 5% NaHCO3 (2×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a crude, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-60%) to yield the desired N-Boc-3-amino-cyclobutanone (7.13 g, 38.53 mmol, 72% yield): NMR (250 MHz, CDCl3) δ 4.88 (bs, 1H), 4.13-4.29 (m, 1H), 3.23-3.41 (m, 2H), 2.9-3.05 (m, 2H), 1.39 (s, 9H).
Reaction SMILES: [N+](=[C:3]1[C:8](=[O:9])[CH2:7][C:6]([CH3:11])([CH3:10])[CH2:5][C:4]1=[O:12])=[N-].ClC1C=CC=CC=1.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1.[C:34]([C:38]1[CH:39]=[C:40]([CH3:45])[CH:41]=[C:42]([CH3:44])[CH:43]=1)([CH3:37])([CH3:36])[CH3:35]>[Hg]>[CH3:45][C:40]1[CH:39]=[C:38]([C:34]([CH3:36])([CH3:35])[CH3:37])[CH:43]=[C:42]([CH3:44])[C:41]=1[CH:3]1[C:8](=[O:9])[CH2:7][C:6]([CH3:11])([CH3:10])[CH2:5][C:4]1=[O:12]
Reactant: Cc1cc(C)cc(C(C)(C)C)c1
Reactant: CC1(C)CC(=O)C(=[N+]=[N-])C(=O)C1
Agent: O=C(c1ccccc1)c1ccccc1
Agent: [Hg]
Solvent: Clc1ccccc1
Product: Cc1cc(C(C)(C)C)cc(C)c1C1C(=O)CC(C)(C)CC1=O
Yield: 11 %

Procedure:
A solution of 7.00 g (0.042 mol) of 2-diazo-5,5-dimethylcyclohexane-1,3-dione in 300 ml of 5-t-butyl-m-xylene and 250 ml chlorobenzene containing 38.38 g (0.21 mol) of benzophenone was irradiated overnight with a 200 watt mercury arc lamp fitted with a borosilicate glass filter after degassing for 1 hour under nitrogen. The photolysis mixture was extracted with 0.25N NaOH, washed with ether, acidified with 1N HCl, and extracted with chloroform. The chloroform was dried over anhydrous MgSO4 and stripped to give a crude yellow solid. The photolysis was repeated and the combined crude product from these reactions was chromatographed through silica gel (0.063-0.2 mm) using benzene-ethyl acetate. The solid obtained from the chromatography was recrystallized from benzene to give 2.76 g (11%) of 2-(2',6'-dimethyl-4'-t-butylphenyl)-5,5-dimethyl-1,3-cyclohexanedione as white crystals, mp 244°-49° C.