Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=S)[CH2:10][N:9]=[C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:7]=2[CH:21]=1.[OH:24][CH2:25][C:26]([NH:28][NH2:29])=O>C(O)CCC>[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[CH:5][C:6]2[N:12]3[C:26]([CH2:25][OH:24])=[N:28][N:29]=[C:11]3[CH2:10][N:9]=[C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:7]=2[CH:21]=1
Reactant: FC(F)(F)c1ccc2c(c1)C(c1ccccc1Cl)=NCC(=S)N2
Reactant: NNC(=O)CO
Solvent: CCCCO
Product: OCc1nnc2n1-c1ccc(C(F)(F)F)cc1C(c1ccccc1Cl)=NC2

Procedure:
In the manner given in Example 1, a solution of 1,3-dihydro-7-trifluoromethyl-5-(o-chlorophenyl)-2H-1,4-benzodiazepine-2-thione and hydroxyacetic acid hydrazide in n-butyl alcohol was refluxed to give 8-trifluoromethyl-1-(hydroxymethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [F:1][C@H:2]1[CH2:6][N:5]([CH2:7][CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[N:17]=3)[N:12]=[CH:11][C:10]=2[F:21])[CH2:4][C@H:3]1[CH2:22][NH2:23].[O:24]=[C:25]1[NH:30][C:29]2[N:31]=[C:32]([CH:35]=O)[CH:33]=[CH:34][C:28]=2[S:27][CH2:26]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[F:1][C@H:2]1[CH2:6][N:5]([CH2:7][CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[N:17]=3)[N:12]=[CH:11][C:10]=2[F:21])[CH2:4][C@H:3]1[CH2:22][NH:23][CH2:35][C:32]1[CH:33]=[CH:34][C:28]2[S:27][CH2:26][C:25](=[O:24])[NH:30][C:29]=2[N:31]=1
Reactant: COc1ccc2ncc(F)c(CCN3C[C@@H](CN)[C@@H](F)C3)c2n1
Reactant: O=Cc1ccc2c(n1)NC(=O)CS2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: COc1ccc2ncc(F)c(CCN3C[C@@H](CNCc4ccc5c(n4)NC(=O)CS5)[C@@H](F)C3)c2n1
Reaction time: 24 h
Yield: 43.4 %

Procedure:
To a stirred solution of (±)-[(cis-4-fluoro-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)methyl]amine (0.15 g, 0.46 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (10 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (0.077 g, 0.46 mmole). After 24 h, at RT was added NaBH(OAc)3 (0.15 g, 0.69 mmole). After 2 h, the reaction solution was concentrated under vacuum and purified on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) to afford the title compound (0.10 g, 46%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.21 (d, J=9.1 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.10 (m, 2H), 4.13 (s, 2H), 4.10 (s, 3H), 3.62 (m, 2H), 3.49-3.43 (m, 6H), 3.21 (m, 2H), 2.99 (m, 2H), 2.32 (app s, 2H). LC-MS (ES) m/e 501 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:3]=1.[NH2:19][CH2:20][CH:21]([OH:24])[CH2:22][NH2:23]>>[ClH:1].[NH2:19][CH2:20][CH:21]([OH:24])[CH2:22][NH:23][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:3]=1
Reactant: NCC(O)CN
Reactant: Cc1ccc(-c2cc(Cl)c3ccccc3n2)cc1
Product: Cc1ccc(-c2cc(NCC(O)CN)c3ccccc3n2)cc1
Product: Cl

Procedure:
The title compound, m.p. 264-272° C. and MS: m/e=308.3 (M+H+), was prepared from 4-chloro-2-p-tolyl-quinoline and 1,3-diamino-2-propanol.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:16]=[N:17][C:18]([N+:21]([O-])=O)=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:16]=[N:17][C:18]([NH2:21])=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCCN(c2ccc([N+](=O)[O-])nc2)CC1
Reactant: [H][H]
Agent: [Pd]
Product: CC(C)(C)OC(=O)N1CCCN(c2ccc(N)nc2)CC1
Yield: 122.4 %

Procedure:
By repeating procedures described in Example B, 4-(6-nitro-pyridin-3-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (490 mg, 1.52 mmol) is hydrogenated over Pd—C on an H-cube (Thales) (instead of under an atmosphere of hydrogen) to give 4-(6-amino-pyridin-3-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (544 mg, 98%). MS (ESI) m/z 293 (M+H)+
Reaction SMILES: CCN(C(C)C)C(C)C.[CH:10]1([C:13](Cl)=[O:14])[CH2:12][CH2:11]1.[CH3:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:24]=[C:25]([NH2:38])[C:26]3[C:30]([CH:31]=2)=[N:29][N:28](C2CCCCO2)[CH:27]=3)[CH:20]=[CH:21][CH:22]=1>C1COCC1>[CH3:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:31]=[C:30]3[C:26]([CH:27]=[N:28][NH:29]3)=[C:25]([NH:38][C:13]([CH:10]3[CH2:12][CH2:11]3)=[O:14])[CH:24]=2)[CH:20]=[CH:21][CH:22]=1
Reactant: Cc1cccc(-c2cc(N)c3cn(C4CCCCO4)nc3c2)c1
Reactant: O=C(Cl)C1CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1cccc(-c2cc(NC(=O)C3CC3)c3cn[nH]c3c2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
THF (1 ml), DIPEA (0.142 ml, 0.813 mmol) and cyclopropanecarbonyl chloride (34 mg, 0.325 mmol) were added to 6-(3-methylphenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (50 mg, 0.163 mmol) and the reaction was stirred at RT for 1 h. The solvent was evaporated under a stream of nitrogen and 2 M sodium hydroxide (aq) (3 ml) was added and the reaction stirred for 1 h. DCM (3 ml) was added and the reaction stirred for a further 30 mins. The organic layer was passed through a hydrophobic frit and the aqueous layer extracted with DCM. The combined organic layers were concentrated. The residue was dissolved in MeOH (2 ml) and 4 M HCl in 1,4-dioxane (2 ml) was added. The reaction was stirred for 1 h then the solvent was removed in vacuo. The residue was purified by MDAP (Method A) then freeze dried to give title compound, 17 mg.
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[N:20]=4)=[N:17][N:16]4[CH2:26][CH2:27][CH2:28][C:15]=34)[CH:12]=2)[N:7]=[CH:6][C:5]1=[O:29].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>O1CCOCC1.C(Cl)(Cl)Cl.C(O)(C)C>[CH3:25][C:21]1[N:20]=[C:19]([C:18]2[C:14]([C:11]3[CH:12]=[C:13]4[C:8]([NH:7][CH2:6][C:5](=[O:29])[N:4]4[CH2:3][CH2:2][N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:9][CH:10]=3)=[C:15]3[CH2:28][CH2:27][CH2:26][N:16]3[N:17]=2)[CH:24]=[CH:23][CH:22]=1
Reactant: C1CCNC1
Reactant: Cc1cccc(-c2nn3c(c2-c2ccc4ncc(=O)n(CCCl)c4c2)CCC3)n1
Solvent: C1COCCO1
Solvent: CC(C)O
Solvent: ClC(Cl)Cl
Product: Cc1cccc(-c2nn3c(c2-c2ccc4c(c2)N(CCN2CCCC2)C(=O)CN4)CCC3)n1
Temperature: 110 °C
Yield: 84 %

Procedure:
Combine 1-(2-chloro-ethyl)-7-[2-[6-methyl-(pyridin-2-yl)]-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-quinoxalin-2-one (Preparation 7; 60 mg, 0.15 mmol) and pyrrolidine (0.5 ml) in dioxane (5 mL) in a pressure tube. Seal the tube and heat at 110° C. for 40 min. Dilute the reaction mixture with 1:1 chloroform/isopropyl alcohol and wash the solution with saturated sodium chloride solution. Dry the organic phase (sodium sulfate), filter, and concentrate in vacuo. Purify the residue by silica gel chromatography (dichloromethane to 1:1 dichloromethane/methanol) to give 54 mg (84%) of the titled compound. MS ES+ m/e 441 (M+1).
Reaction SMILES: [F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][C:35]=5[CH3:44])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22](S(C)(=O)=O)[N:21]=3)[C@H:14]2[CH3:49])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:52]1[CH:56]=[CH:55][N:54]=[CH:53]1>O1CCOCC1>[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][C:35]=5[CH3:44])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:52]4[CH:56]=[CH:55][N:54]=[CH:53]4)[N:21]=3)[C@H:14]2[CH3:49])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: c1c[nH]cn1
Reactant: COC(=O)c1ccc(-c2cnc(OC)c(-c3cnc(S(C)(=O)=O)nc3CN3C(=O)O[C@H](c4cc(C(F)(F)F)cc(C(F)(F)F)c4)[C@@H]3C)c2)c(C)c1
Solvent: C1COCCO1
Product: COC(=O)c1ccc(-c2cnc(OC)c(-c3cnc(-n4ccnc4)nc3CN3C(=O)O[C@H](c4cc(C(F)(F)F)cc(C(F)(F)F)c4)[C@@H]3C)c2)c(C)c1
Reaction time: 8 h

Procedure:
Methyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfonyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate (INTERMEDIATE 46, 125 mg, 0.169 mmol), 1,4-dioxane (1.1 mL) and imidazole (57.6 mg, 0.846 mmol) were stirred at 80° C. for 20 minutes in a 1 dram vial. LCMS shows about 2/3 conversion to target. Dropped temperature to 40° C., and stirred overnight, at which time LCMS showed reaction is complete. The reaction was directly purified by silica gel chromatography, eluting with 20-100% ethyl acetate/hexanes to give the titled compound. 1H NMR (CDCl3, 500 MHz): δ 8.64 (s, 1H), 8.56 (s, 1H), 8.30 (d, 1H), 8.00 (s, 1H), 7.94 (d, 1H), 7.90 (s, 2H), 7.75 (s, 2H), 7.57 (d, 1H), 7.33 (d, 1H), 7.22 (s, 1H), 5.75 (d, 1H), 4.91 (d, 1H), 4.46 (m, 1H), 4.20 (d, 1H), 4.03 (s, 3H), 3.94 (s, 3H), 2.39 (s, 3H), 0.81 (d, 3H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1)=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:28])=CC=1>C1COCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1)=[S:28]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CN1CCN(C(=O)c2cc3ccccc3[nH]2)CC1
Solvent: C1CCOC1
Product: CN1CCN(C(=S)c2cc3ccccc3[nH]2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 15.3 %

Procedure:
(1H-Indol-2-yl)-(4-methyl-piperazin-1-yl)-methanone (Example 4, 0.123 g) in THF (1 mL) was treated with Lawesson's reagent (0.243 g) and stirred at ambient temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified via preparative thin layer chromatography to afford the title compound (0.02 g). 1H NMR (400 MHz, CDCl3): δ 9.21 (br s, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 7.29 (d, J=7.3 Hz, 1H), 7.12 (m, 1H), 6.60 (s, 1H), 4.39 (br s, 4H), 3.85 (br s, 4H), 2.63 (s, 3H).
Reaction SMILES: [CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]2=[CH:13][S:14][CH:15]=[C:4]2[C:3]1=[O:16].[C:17](Cl)(=[O:20])[CH2:18][CH3:19]>C1C=CC=CC=1>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:17](=[O:20])[CH2:18][CH3:19])[C:5]2=[CH:13][S:14][CH:15]=[C:4]2[C:3]1=[O:16]
Reactant: CN1C(=O)c2cscc2Nc2ccccc21
Reactant: CCC(=O)Cl
Solvent: c1ccccc1
Product: CCC(=O)N1c2cscc2C(=O)N(C)c2ccccc21
Reaction time: 48 h

Procedure:
A reaction mixture comprising 7 g. of 4,9-dihydro-9-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one, 3.1 g. (2.9 ml.) of propionyl chloride and 70 ml. of benzene is refluxed for 3 hours and then allowed to stand for 48 hours. The benzene is distilled off. The residue is filtered, washed with ether and dried. The solid is heated to boiling in 300 ml. of ethyl acetate, filtered and the filtrate is chilled. The crystals are collected, washed with ether and dried giving the desired product, mp. 202°-203° C.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH2:12]([N:14]([S:37]([C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=1)(=[O:39])=[O:38])[C:15](=[CH2:36])[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[CH:21]=1)=[O:17])[CH3:13].O.C([O-])([O-])=O.[K+].[K+]>C(Cl)(Cl)Cl>[CH2:12]([N:14]([S:37]([C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=1)(=[O:39])=[O:38])[C:15](=[CH2:36])[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][N+:23]([O-:9])=[C:22]([C:26]2[CH:27]=[CH:28][C:29]([C:32]([F:33])([F:34])[F:35])=[CH:30][CH:31]=2)[CH:21]=1)=[O:17])[CH3:13]
Reactant: C=C(C(=O)NCc1ccnc(-c2ccc(C(F)(F)F)cc2)c1)N(CC)S(=O)(=O)c1ccc(F)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: O
Product: C=C(C(=O)NCc1cc[n+]([O-])c(-c2ccc(C(F)(F)F)cc2)c1)N(CC)S(=O)(=O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 29 %

Procedure:
3-Chloro perbenzoic acid (1.5 mol eq, 100 mg) was added to a solution of Example 1 (200 mg, 0.39 mmol) in CHCl3 (10 mL) and the mixture was stirred at r.t. for 24 hours. Then 10% water solution of K2CO3 was added to wash the organic phase that was then dried over Na2SO4 and evaporated under reduced pressure. The resulting residue was purified by flash chromatography (EtOAc 6/petroleum ether 4) to obtain a white solid (60 mg, 29% yield). 1HNMR (DMSO, 200 MHz) δ 1.09 (3H, t, J=7.2 Hz), 3.40 (2H, q, J=6.8 Hz), 4.40 (2H, d, J=6 Hz), 5.14 (1H, s), 6.10 (1H, s), 7.36 (1H, dd, J=4.8 Hz, J′=1.2 Hz), 7.46 (2H, t, J=8.8 Hz), 7.63 (1H, d, J=2.2 Hz), 7.83 (4H, m), 8.05 (2H, d, J=8 Hz), 8.34 (1H, d, J=6.8 Hz), 8.82 (1H, bt) [M+1] 524.6 (C24H21F4N3O4S requires 523.50).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([Cl:16])[N:3]=1.[NH:17]1[CH2:22][CH2:21][CH:20]([N:23]2[C:28](=[O:29])[CH2:27][C:26]3([CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)[CH2:25][C:24]2=[O:35])[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[ClH:16].[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([CH:22]2[CH2:21][CH:20]([N:23]3[C:28](=[O:29])[CH2:27][C:26]4([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)[CH2:25][C:24]3=[O:35])[CH2:19][CH2:18][NH:17]2)[N:3]=1
Reactant: COc1cc2nc(Cl)nc(N)c2cc1OC
Reactant: O=C1CC2(CCCCC2)CC(=O)N1C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc2nc(C3CC(N4C(=O)CC5(CCCCC5)CC4=O)CCN3)nc(N)c2cc1OC
Product: Cl
Reaction time: 10 h

Procedure:
The mixture of 2.39 g of 4-amino-2-chloro-6,7-dimethoxyquinazoline, 2.64 g of 3-(4-piperidinyl)-3-azaspiro-[5,5]-undecan-2,4-dione, 2.1 g anhydrous sodium carbonate and 25 ml of dimethylformamide is stirred under nitrogen at 150° for 10 hours. It is filtered, the filtrate evaporated, the residue dissolved in methylene chloride, the solution washed with aqueous sodium carbonate, dried, filtered and evaporated. The residue is triturated with 50 ml of isopropanol, the remainder taken up in isopropanol and the mixture acidified with hydrogen chloride, to yield the 3-[2-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]-3-azaspiro[5,5]undecan-2,4-dione monohydrochloride melting at 290° (dec.).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>C1(C)C=CC=CC=1.O>[CH3:19][S:20]([O:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=1)(=[O:22])=[O:21]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)c1cccc(O)c1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)c1cccc(OS(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 0.1 %

Procedure:
8.00 g (53.3 mol) of 3-tert-butylphenol and 5.93 g (58.6 mol) of triethylamine were dissolved in 80 mL of toluene followed by dropping in 6.71 g (58.6 mol) of methanesulfonyl chloride over the course of 10 minutes at 10° C. followed by stirring for 10 minutes at 25° C. and confirming the 3-tert-butylphenol to no longer be present by gas chromatography. The reaction liquid was placed in water and following separation of the organic layer, was washed three times with water, once with saturated aqueous NaHCO3 solution and once with saturated brine followed by drying with MgSO4, concentrating and purifying the resulting residue by vacuum distillation to obtain 10.7 g (yield: 88%) of 3-tert-butylphenyl methanesulfonate.
Reaction SMILES: F.[F-].[U+2:3](=O)=[O:4].[F-]>O>[O-2:4].[O-2:4].[O-2:4].[O-2:4].[O-2:4].[O-2:4].[O-2:4].[O-2:4].[U+6:3].[U+6:3].[U+6:3]
Reactant: O=[U+2]=O
Agent: F
Agent: [F-]
Solvent: O
Product: [O-2]
Product: [U+6]

Procedure:
A method is provided for recovering an anhydrous hydrogen fluoride product from uranium hexafluoride gas by initially reacting the uranium hexafluoride in a primary reactor with steam to produce a uranyl fluoride intermediate and a gaseous mixture of hydrogen fluoride and water. The uranyl fluoride intermediate is fed to a secondary reactor and reacted with water to produce a triuranium octoxide product for disposal, and a gaseous mixture of water, hydrogen fluoride and oxygen. The two mixtures from the primary and secondary reactors are combined and subsequently separated in a distillation column to obtain an anhydrous hydrogen fluoride product stream and an aqueous azeotropic recycle stream containing water and hydrogen fluoride which is vaporized and returned to the primary reactor as the steam feed.
Reaction SMILES: [CH2:1]([C@H:5]1[CH2:9]C[CH:7](C#N)[CH2:6]1)[CH2:2][CH2:3][CH3:4].S(=O)(=O)(O)O.[C:17]([OH:20])(=[O:19])[CH3:18]>O.C(OCC)(=O)C>[CH2:1]([C@H:5]1[CH2:6][CH2:7][CH:18]([C:17]([OH:20])=[O:19])[CH2:9]1)[CH2:2][CH2:3][CH3:4]
Reactant: CC(=O)O
Reactant: CCCC[C@H]1CCC(C#N)C1
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Solvent: O
Product: CCCC[C@H]1CCC(C(=O)O)C1
Reaction time: 1 h
Yield: 36.5 %

Procedure:
A mixture of 73 mg of (1RS,3S)-3-butyl-1-cyanocyclopentane (prepared in Reference Example 13), 0.6 ml of conc. sulphuric acid, 0.6 ml of acetic acid and 0.6 ml of water was stirred for 1 hr. at 110° C. To the reaction solution, 30 ml of ethyl acetate and 20 ml of water were added. The oily layer which separated was washed with water, dried over anhydrous magnesium sulphate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate (2:1) as eluent to give 30 mg of the title compound having the following physical characteristics, in a 36.5% yield.
Reaction SMILES: C(O[C:6](=O)[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])(C)(C)C.[CH:14](=O)[CH2:15][CH3:16].C([BH3-])#N.[Na+].[C:22](OC)(OC)(OC)[CH3:23]>CO>[CH2:14]([N:7]([CH2:6][CH2:22][CH3:23])[CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH2:15][CH3:16]
Reactant: CCC=O
Reactant: COC(C)(OC)OC
Reactant: CC(C)(C)OC(=O)NCCCCN
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CCCN(CCC)CCCCN
Temperature: 25 °C
Reaction time: 12 h

Procedure:
N-(4-aminobutyl)-carbamic acid t-butyl ester (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (500 mg) was dissolved in methanol (10 ml) and then added with propionaldehyde (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (0.418 ml), sodium cyanoborohydride (404 mg), and trimethyl orthoacetate (1.60 g), and the whole was stirred at room temperature for 12 hours. After completion of the reaction, the solvent was distilled off. Then, the resultant was added with chloroform, washed with distilled water and a saturated saline solution, and then dried with anhydrous sodium sulfate. After concentration and evaporation to dryness of the solution, methanol (4.0 ml) and a 4 mol/l hydrogen chloride/dioxane solution (4.0 ml) were added to the dried product and the whole was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was distilled off and then dioxane was added to wash the residue, thereby obtaining a hydrochloride (654 mg) of the subject compound.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]2[O:15][CH:3]12)=[N:10][O:11][N:12]=3.[NH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1>C(O)C>[CH3:1][C:2]1([CH3:16])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:3]1[OH:15])=[N:10][O:11][N:12]=3
Reactant: C1CCNC1
Reactant: CC1(C)Oc2cc3nonc3cc2C2OC21
Solvent: CCO
Product: CC1(C)Oc2cc3nonc3cc2C(N2CCCC2)C1O
Reaction time: 31 h
Yield: 60 %

Procedure:
A mixture of 150 mg (0.687 m mol) of 7,8-dihydro-6,6-dimethyl-7,8-epoxy-6H-pyrano [2,3-f] benzo-2,1,3-oxadiazole, 63 μl (0.756 m mol) of pyrrolidine and 2 ml of ethanol was refluxed with stirring for 31 hours. After the solvent was distilled off, the residue was subjected to a preparative silica gel thin layer chromatography using a developing solvent of ethyl acetate-methanol (1:1 (v/v)) to obtain 120 mg (yield: 60%) of the intended compound. A part of the obtained compound was dissolved in dry ether and added with HCl--EtOH to obtain hydrochloride of the intended compound as pale yellow crystals.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:12]2=[C:13]([N+:28]([O-])=O)[C:14]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=3[F:27])=[C:15]([CH3:18])[C:16](=[O:17])[N:11]2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+].[Cl-].C(OC(=O)C)C>O.C1COCC1.[Zn]>[C:1]([O:5][C:6]([N:8]1[C:12]2=[C:13]([NH2:28])[C:14]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][C:21]=3[F:27])=[C:15]([CH3:18])[C:16](=[O:17])[N:11]2[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1c(Nc2ccc(Br)cc2F)c([N+](=O)[O-])c2n(c1=O)CCN2C(=O)OC(C)(C)C
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(Nc2ccc(Br)cc2F)c(N)c2n(c1=O)CCN2C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 47.3 %

Procedure:
Zinc (284 mg, 0.004 mol) was added to a stirred solution of 7-(4-bromo-2-fluoro-phenylamino)-6-methyl-8-nitro-5-oxo-2,3-dihydro-5H-imidazo[1,2-a]pyridine-1-carboxylic acid tert-butyl ester (350 mg, 0.0007 mol) and NH4Cl (310 mg, 0.006 mol) in water and THF (10 mL). The resulting mixture was stirred at room temperature for 40 minutes. The reaction was monitored by TLC (100% ethylacetate). The reaction mixture was concentrated and partitioned between ethylacetate and water. The organic layer was washed with saturated NaHCO3 solution and concentrated to afford 150 mg of the crude product which was used in the next step without further purification.
Reaction SMILES: CCCCCC.[H-].[Na+].[CH3:9][O:10][C:11]([CH2:13]P(OC)(OC)=O)=[O:12].[Cl:20][C:21]1[CH:31]=[C:30]([CH2:32][CH2:33][CH3:34])[CH:29]=[C:28]([CH:35]=O)[C:22]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24]>C1COCC1>[Cl:20][C:21]1[CH:31]=[C:30]([CH2:32][CH2:33][CH3:34])[CH:29]=[C:28](/[CH:35]=[CH:13]/[C:11]([O:10][CH3:9])=[O:12])[C:22]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24]
Reactant: COC(=O)CP(=O)(OC)OC
Reactant: CCCc1cc(Cl)c(C(=O)OCC)c(C=O)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCc1cc(Cl)c(C(=O)OCC)c(/C=C/C(=O)OC)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.3 %

Procedure:
To a suspension of hexane-washed sodium hydride (0.14 g of 60% suspension in mineral oil, 3.45 mmol) in 20 mL of THF was added trimethyl phosphonoacetate (0.56 mL, 3.45 mmol). The resulting mixture was stirred for 30 min at ambient temperature, at which time a white slurry was obtained. To this slurry was added ethyl 2-chloro-6-formyl-4-propylbenzoate (0.80 g, 3.14 mmol) dropwise in 5 mL of THF. The resulting solution was stirred at ambient temperature for 1 h, at which time the mixture had become homogeneous. The reaction mixture was quenched with water and extracted with ethyl acetate. The organics were washed sequentially with 1N HCl, sat'd aq NaHCO3 and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated in vacuo to afford 0.92 g (95%) of the title compound which was sufficiently pure to be used without purification. 1H NMR (CDCl3): δ 7.58 (d, 1H, J=15.9 Hz), 7.25 (s, 1H), 7.18 (s, 1H), 6.33 (d, 1H, J=15.9 Hz), 4.40 (q, 2H, J=7.2 Hz), 3.73 (s, 3H), 2.52 (t, 2H, J=7.5 Hz), 1.60-1.52 (m, 2H), 1.35 (t, 3H, J=7.1 Hz), 0.88 (t, 3H, J=7.4 Hz). LRMS (ESI): 333.1 (M+H+Na)+.