Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:35]1[CH:36]=[CH:37][C:38]([C:41]([CH:52]2[CH2:54][CH2:53]2)([CH:49]2[CH2:51][CH2:50]2)[NH:42][S@@:43]([C:45]([CH3:48])([CH3:47])[CH3:46])=[O:44])=[N:39][CH:40]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:49]1([C:41]([CH:52]2[CH2:54][CH2:53]2)([C:38]2[CH:37]=[CH:36][C:35]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[N:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][N:19]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)=[CH:40][N:39]=2)[NH:42][S@@:43]([C:45]([CH3:47])([CH3:48])[CH3:46])=[O:44])[CH2:51][CH2:50]1
Reactant: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: CC(C)(C)[S@@](=O)NC(c1ccc(Br)cn1)(C1CC1)C1CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Product: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2ccc(C(N[S@](=O)C(C)(C)C)(C3CC3)C3CC3)nc2)c1

Procedure:
N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (300 mg, 0.791 mmol), PdCl2(dppf)-dichloromethane adduct (32.3 mg, 0.040 mmol), and sodium carbonate (2 M, 0.791 mL, 1.58 mmol) were added to a solution of (R)—N-[(5-bromopyridin-2-yl)(dicyclopropyl)methyl]-2-methylpropane-2-sulfinamide (344 mg, 0.926 mmol) in 2-methyl-THF (2.60 mL) and flushed and purged with Ar(g). The reaction mixture was irradiated in a microwave reactor for 5 minutes at 170° C. Upon cooling, the reaction mixture was diluting with saturated aqueous NaHCO3 (10.0 mL) and extracted with ethyl acetate (20.0 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by silica gel chromatography (0.5-3% methanol in dichloromethane) to yield (R)—N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}-2-methylpropane-2-sulfinamide. MS APCI calc'd for C28H33F3N5OS [M+H]+ 544. found 544.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:13]([O:14][C:15](=[O:17])[CH3:16])[C@@H:12]([CH2:18][O:19]C(=O)C)[O:11][C@H:7]([S:8][CH2:9][CH3:10])[C@H:6]1[N:23]=[N+:24]=[N-:25])(=[O:3])[CH3:2].CC(O)=O.[Si:30](Cl)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]>CO>[C:1]([O:4][C@H:5]1[C@H:13]([O:14][C:15](=[O:17])[CH3:16])[C@@H:12]([CH2:18][O:19][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[O:11][C@H:7]([S:8][CH2:9][CH3:10])[C@H:6]1[N:23]=[N+:24]=[N-:25])(=[O:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CCS[C@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1N=[N+]=[N-]
Solvent: CC(=O)O
Solvent: CO
Product: CCS[C@H]1O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.5 %

Procedure:
To a solution of 22 (3.71 g, 9.88 mmol) in MeOH (30 mL) NaOMe (1 M) was added. The mixture was neutralized with AcOH after 1 h and concentrated. The dry residue was dissolved in pyridine (15 mL) and tert-butyldimethylsilyl chloride (1.94 g, 12.87 mmol) was added. The reaction mixture was stirred at rt overnight. Acetylation with acetic anhydride, dilution with toluene, filtration (silica), concentration and purification by chromatography (1:0→1:1 toluene-EtOAc) gave 23 (4.357 g, 9.73 mmol, 99%); [α]D+109° (c 1.0, CHCl3); 13C NMR δ −5.33, −5.28 (CH3Si), 14.7 (SCH2CH3), 18.4 ((CH3)3CSi), 20.7, 20.9 (CH3CO), 25.0 (SCH2CH3), 25.9 ((CH3)3CSi), 62.6, 62.9, 67.0, 71.7, 71.9 (C-2-6), 81.5 (C-1), 169.7, 170.1 (CH3CO); 1H NMR δ 0.05 (s, 3H), 0.05 (s, 3H), 0.90 (s, 9H), 1.30 (t, 3H), 2.05 (s, 3H), 2.10 (s, 3H), 2.55-2.75 (m, 2H), 3.60-3.75 (m, 2H), 4.10 (m, 1H), 4.15-4.20 (m, 1H), 5.20-5.25 (m, 1H), 5.30-5.35 (m, 1H); HRMS calcd for C18H33N3NaO6SSi [M+Na]+ 470.1757, found 470.1750.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]=[C:13]=[O:14])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[CH3:15][NH:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:25][CH:24]=2)[CH:20]=[CH:21][CH:22]=1>>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:14])[N:16]([C:17]2[CH:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:25][CH:24]=3)[CH:20]=[CH:21][CH:22]=2)[CH3:15])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(=O)CCc1ccc(-c2cccc(NC)c2)cc1
Reactant: CCCCOc1ccc(N=C=O)cc1
Product: CCCCOc1ccc(NC(=O)N(C)c2cccc(-c3ccc(CCC(=O)OCC)cc3)c2)cc1
Yield: 97.4 %

Procedure:
In a manner similar to that of Example (5a), by reaction of 574 μl (3.17 mmol, 3 eq) of 4-butoxyphenyl isocyanate and 300 mg (1.06 mmol, 1 eq) of ethyl 3-(3′-methylaminobiphenyl-4-yl)propanoate at 100° C. by microwave for 15 minutes, 490 mg of ethyl 3-{3′-[3-(4-butoxyphenyl)-1-methylureido]biphenyl-4-yl}propanoate are obtained in the form of a white solid. Yield=97%
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[C:9]([CH2:11][CH3:12])[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:13][C:14]1[S:15][C:16]([CH3:19])=[N:17][N:18]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(O)(C)C>[CH2:11]([C:9]1[S:8][C:4]2[N:5]=[CH:6][N:7]=[C:2]([NH:13][C:14]3[S:15][C:16]([CH3:19])=[N:17][N:18]=3)[C:3]=2[CH:10]=1)[CH3:12]
Reactant: CCc1cc2c(Cl)ncnc2s1
Reactant: Cc1nnc(N)s1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [Na+]
Solvent: CC(C)O
Product: CCc1cc2c(Nc3nnc(C)s3)ncnc2s1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of Example 1C (0.20 g, 1.01 mmol) in isopropanol (2 mL) was treated with 2-amino-5-methyl-1,3,4-thiadiazole (0.115 g, 1.726 mmol) and sodium carbonate (0.18 g, 1.7 mmol), stirred at room temperature for 48 hours, treated with cesium carbonate (0.55 g, 1.7 mmol), stirred at reflux for 24 hours, concentrated, treated with water, and extracted with dichloromethane. The extract was dried (MgSO4), filtered, and concentrated. The residue was recrystallized with ethanol/water to provide the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.[H-].[Na+].[Cl:11][CH2:12][CH2:13][CH2:14]I.[Na+].[Cl-]>CN(C)C=O.O>[Cl:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH2:14][CH2:13][CH2:12][Cl:11])[CH:3]=1
Reactant: Oc1cncc(Cl)c1
Reactant: ClCCCI
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: ClCCCOc1cncc(Cl)c1
Temperature: 25 °C
Yield: 72.2 %

Procedure:
Under a nitrogen atmosphere, a solution of 5-chloro-3-pyridinol (15.00 g, 115.8 mmol) in N,N-dimethylformamide (DMF) (10 mL) was added drop-wise over 5 min to a cold (0-5° C.), stirring slurry of sodium hydride (3.69 g of an 80% dispersion in mineral oil, 123.0 mmol) in DMF (15 mL). The mixture was allowed to stir and warm to ambient temperature over 1 h. Next, 1-chloro-3-iodopropane (28.4 g, 138.9 mmol) was added drop-wise over 5 min. The resulting dark-brown mixture was stirred at ambient temperature for 4 h. Water (25 mL) was added, followed by saturated NaCl solution (25 mL), and the mixture was extracted with ether (4×50 mL). The combined ether extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give 17.22 g (73.0%) of an oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[OH:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[N:28]1[CH:33]=[CH:32][C:31]([CH2:34]Cl)=[CH:30][CH:29]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:34][C:31]2[CH:32]=[CH:33][N:28]=[CH:29][CH:30]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccccc2O)CC1
Reactant: ClCc1ccncc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(c2ccccc2OCc2ccncc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 67.7 %

Procedure:
A mixture of 4-(2-Hydroxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (18 mmol, 5 g), DMF (40 ml) and cesium carbonate (40 mmol, 13 g) was stirred at room temperature for 15 minutes, followed by addition of 4-picolyl chloride hydrochloride (18 mmol, 2.953 g). The resulting mixture was stirred at room temperature overnight. The reaction mixture was poured onto ice/water and extracted with ethyl acetate (3×). The combined organic layer was washed with Sat. NaCl. The crude product was purified on silica column using 75% EtOAc/hexanes to give 4-[2-(Pyridin-4-ylmethoxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester (4.5 g).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4](=[O:7])[CH2:3][CH:2]=1.C(O[C@@H:12]1[O:34][C@H:33]([CH2:35][O:36][C:37](=[O:44])[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:23]([O:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:13]1[O:14][C:15](=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=O)C.[K].FC(F)(S(O)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.C[Si](N[Si](C)(C)C)(C)C>C(OCC)(=O)C.CO.C(#N)C>[C:15]([O:14][C@@H:13]1[C@H:23]([O:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:33]([CH2:35][O:36][C:37](=[O:44])[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[O:34][C@H:12]1[N:1]1[CH:2]=[CH:3][C:4](=[O:7])[CH:5]=[CH:6]1)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(=O)O[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Reactant: O=C1C=CN=CC1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: O=S(=O)(O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: [K]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CC#N
Product: O=C(OC[C@H]1O[C@@H](n2ccc(=O)cc2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1

Procedure:
0.47 g. (5 mmol) of 4-pyridone, 2.52 g. (5 mmol) of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose, and 4.06 g. (12 mmol) of the potassium salt of perfluorobutanesulfonic acid were refluxed with 0.29 g. (1.75 mmol) of HMDS and 1.49 g. (13.75 mmol) of TCS in 70 ml. of absolute acetonitrile for 12 hours. The usual working-up step (Example 1) yielded after chromatography on silica gel with ethyl acetate-methanol (95:5) 65% of amorphous 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-pyridone.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:32]#[N:33])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([C:16](=[CH:24][C:25]3([CH2:29][CH3:30])[CH2:28][O:27][CH2:26]3)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:31])[CH:9]=2)[CH:7]=1>[Cl-].[NH4+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:32]#[N:33])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH2:29][CH3:30])[CH2:26][O:27][CH2:28]3)[C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[C:10](=[O:31])[CH:9]=2)[CH:7]=1
Reactant: CCC1(C=C(C(=O)OC(C)(C)C)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)COC1
Agent: [Cl-]
Agent: [NH4+]
Product: CCC1(CC(C(=O)OC(C)(C)C)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)COC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
At RT, 302 mg (641 μmol) of tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-ethyloxetan-3-yl)prop-2-enoate (isomer mixture) were admixed with 20 ml of a “Hot Stryker's” reagent solution [B. A. Baker et al. Org. Lett. 2008, 10, 289-292]. The reaction mixture was stirred at RT for 1.5 h, and 20 ml of saturated aqueous ammonium chloride solution were then added. After phase separation, the aqueous phase was extracted three times with 25 ml of ethyl acetate. The combined organic phases were dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The residue was purified by flash chromatography (120 g silica cartridge, 85 ml/min, cyclohexane/ethyl acetate gradient). Yield: 275 mg (91% of theory)
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]1([C:31]2[C:32]3[CH:33]=[CH:34][C:35]([C:65](=[O:73])[NH:66][S:67]([CH:70]([CH3:72])[CH3:71])(=[O:69])=[O:68])=[CH:36][C:37]=3[N:38]3[CH2:44][C:43]([C:45]4[N:49]([CH:50]5[CH2:52][CH2:51]5)[N:48]=[C:47]([CH:53]([CH3:55])[CH3:54])[C:46]=4[C:56]([OH:58])=O)=[CH:42][C:41]4[CH:59]=[C:60]([O:63][CH3:64])[CH:61]=[CH:62][C:40]=4[C:39]=23)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.[CH3:74][C@H:75]1[O:80][C@@H:79]([CH3:81])[CH2:78][NH:77][CH2:76]1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:25]1([C:31]2[C:32]3[CH:33]=[CH:34][C:35]([C:65]([NH:66][S:67]([CH:70]([CH3:72])[CH3:71])(=[O:69])=[O:68])=[O:73])=[CH:36][C:37]=3[N:38]3[CH2:44][C:43]([C:45]4[N:49]([CH:50]5[CH2:52][CH2:51]5)[N:48]=[C:47]([CH:53]([CH3:55])[CH3:54])[C:46]=4[C:56]([N:77]4[CH2:76][C@H:75]([CH3:74])[O:80][C@H:79]([CH3:81])[CH2:78]4)=[O:58])=[CH:42][C:41]4[CH:59]=[C:60]([O:63][CH3:64])[CH:61]=[CH:62][C:40]=4[C:39]=23)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1
Reactant: COc1ccc2c(c1)C=C(c1c(C(=O)O)c(C(C)C)nn1C1CC1)Cn1c-2c(C2CCCCC2)c2ccc(C(=O)NS(=O)(=O)C(C)C)cc21
Reactant: C[C@@H]1CNC[C@H](C)O1
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: COc1ccc2c(c1)C=C(c1c(C(=O)N3C[C@@H](C)O[C@@H](C)C3)c(C(C)C)nn1C1CC1)Cn1c-2c(C2CCCCC2)c2ccc(C(=O)NS(=O)(=O)C(C)C)cc21
Reaction time: 2 h
Yield: 30.7 %

Procedure:
HATU (65.0 mg, 0.171 mmol) was added to a stirring solution of 5-(13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepin-6-yl)-1-cyclopropyl-3-isopropyl-1H-pyrazole-4-carboxylic acid (78 mg, 0.114 mmol), cis-2,6-dimethylmorpholine (28 μL, 0.23 mmol), DIEA (80 μL, 0.456 mmol) in DMF (1 mL) at room temperature. The reaction was allowed to stir for 2 hours. The reaction was purified by preparative reverse phase HPLC on a C18 column using a TFA buffered H2O/CH3CN gradient, and concentrated to give the titled compound (28 mg, 0.035 mmol, 31% yield) consistent by LCMS and NMR, with sufficient purity by HPLC.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][C:9]=1[N+:20]([O-])=O)([CH3:4])([CH3:3])[CH3:2]>[Pd]>[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][C:9]=1[NH2:20])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2)cc1[N+](=O)[O-]
Agent: [Pd]
Product: CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2)cc1N
Yield: 93.4 %

Procedure:
Prepared from (3-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example B5) (100 mg, 0.32 mmol) by catalytic hydrogenation with Pd/C according to the general procedure G (method a). Obtained as a white solid (85 mg).
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][NH:3]1.I[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[K+].[K+].[OH-].[NH4+]>[Cu](I)I.C(OCC)(=O)C.CS(C)=O>[O:1]=[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][N:3]1[C:11]1[CH:12]=[CH:13][C:14]([O:17][C:18]([F:19])([F:20])[F:21])=[CH:15][CH:16]=1
Reactant: FC(F)(F)Oc1ccc(I)cc1
Reactant: O=Cc1ccc[nH]c1=O
Agent: I[Cu]I
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: O=Cc1cccn(-c2ccc(OC(F)(F)F)cc2)c1=O
Temperature: 130 °C
Yield: 19.9 %

Procedure:
2-oxo-1,2-dihydropyridine-3-carbaldehyde 1-1 (200 mg, 1.63 mmol), 1-iodo-4-(trifluoromethoxy)benzene 2-1 (562 mg, 1.95 mmol), 8-hydroxyquinoline (47.2 mg, 0.324 mmol), copper iodide (61.9 mg, 0.324 mmol), and potassium carbonate (303 mg, 2.19 mmol) were combined in a round bottom flask with DMSO (3.5 mL) under a nitrogen atmosphere and heated to 130° C. for 21 h. The reaction was cooled to room temperature and poured into a mixture of 10% aq. ammonium hydroxide and ethyl acetate. The resultant mixture was filtered through a pad of Celite and washed with ethyl acetate three times. The layers were separated with the aqueous portion being back extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification by flash column chromatography on silica gel (0-50% EtOAc in hexane) gave 92.0 mg (20%) of 2-2 as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 10.34 (1H, d, J=0.8 Hz), 8.14 (1H, dd, J=6.9, 2.3 Hz), 7.65 (1H, dd, J=6.9, 2.3 Hz), 7.45 (2H, m), 7.38 (2H, m), 6.44 (1H, dt, J=0.8, 6.9 Hz); ESI-MS m/z 284 [C13H8F3NO3+H]+.
Reaction SMILES: C([NH:14][C:15]1([P:21]([OH:23])[OH:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)(C1C=CC=CC=1)C1C=CC=CC=1.C(NC(P(O)O)C(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>>[NH2:14][C:15]1([P:21]([OH:23])[OH:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: OP(O)C1(NC(c2ccccc2)c2ccccc2)CCCCC1
Agent: CC(C)C(NC(c1ccccc1)c1ccccc1)P(O)O
Product: NC1(P(O)O)CCCCC1

Procedure:
The procedure described in Example 1C was repeated using 1-benzhydrylaminocyclohexanephosphonous acid as starting material instead of DL-1-benzhydrylamino-2-methylpropanephosphonous acid to give 1-aminocyclohexanephosphonous acid of melting point 228°-229° (dec.).
Reaction SMILES: C[O:2][C:3](=[O:51])[CH2:4][CH2:5][C@H:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][C@@H:24]2[OH:27])[C@:20]2([CH3:21])[C@@H:15]([CH2:16][C@@H:17]([NH:28][C:29](=[O:49])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH2:18][CH2:19]2)[CH2:14][C@H:13]3[OH:50])[CH2:10][CH2:9]1)[CH3:7].[OH-].[Na+]>CO>[C:29]([NH:28][C@H:17]1[CH2:18][CH2:19][C@@:20]2([CH3:21])[C@H:15]([CH2:14][C@@H:13]([OH:50])[C@@H:12]3[C@@H:22]2[CH2:23][C@H:24]([OH:27])[C@@:25]2([CH3:26])[C@H:11]3[CH2:10][CH2:9][C@@H:8]2[C@H:6]([CH3:7])[CH2:5][CH2:4][C:3]([OH:51])=[O:2])[CH2:16]1)(=[O:49])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48]
Reactant: CCCCCCCCCCCCCCCCCCCC(=O)N[C@H]1CC[C@@]2(C)[C@@H](C1)C[C@@H](O)[C@@H]1[C@@H]2C[C@H](O)[C@]2(C)[C@@H]([C@H](C)CCC(=O)OC)CC[C@@H]12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCCCCCCCCCCCCCCCCC(=O)N[C@H]1CC[C@@]2(C)[C@@H](C1)C[C@@H](O)[C@@H]1[C@@H]2C[C@H](O)[C@]2(C)[C@@H]([C@H](C)CCC(=O)O)CC[C@@H]12
Reaction time: 24 h
Yield: 142.8 %

Procedure:
0.5 g 3β-arachidylamido-7α,12α-dihydroxy-5β-cholan-24-oic methylester (FIGS. 1A-4) were dissolved in 20 ml methanol, treated with 2 ml 1N sodium hydroxide and left for 24 h at room temperature. The methanol was then distilled off, 10 ml water were added and the reaction mixture was extracted with ethyl acetate. The water fraction was then acidified with diluted hydrogen chloride, resulting in a white precipitate which was washed with water, to give 0.7 g of the pure 3β-arachidylamido-7α,12α-dihydroxy-5β-cholan-24-oic acid (FIGS. 1A-5).
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[CH2:8]([NH2:17])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>CC(C)=O>[CH2:8]([NH:17][C:1](=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCN
Reactant: O=C1CCC(=O)O1
Solvent: CC(C)=O
Product: CCCCCCCCCNC(=O)CCC(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 79.7 %

Procedure:
To a stirred solution of succinic anhydride (25.0 g, 0.25 mol) in 150 mL acetone was added dropwise 35.8 g (0.25 mol) of nonylamine. The addition of the amine required 15 minutes, with the acetone solution reaching reflux before the addition was complete. Five minutes after the end of addition, a precipitate formed and the reaction mixture quickly became thick with suspended solids. Following addition of the amine the reaction mixture was stirred at room temperature for 1 hr. The precipitated solid was collected by filtration and washed with cold acetone. Air drying afforded 48.5 g of 4-nonylamino-4-oxobutyric acid as white, fluffy crystals, mp 114°-115.5° C. Upon standing the filtrate deposited crystals which were collected by filtration, washed with cold acetone, and air dried to yield an additional 10.9 g of the acid, mp 114°-115.5° C. Total yield was 59.4 g (98% of theoretical).
Reaction SMILES: [S:1](=[O:5])(=[O:4])([OH:3])[OH:2].S([O-])([O-])(=O)=[O:7].[Ni+2:11]>O>[S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[Ni+2:11].[OH-:7].[Ni+2:11].[OH-:2]
Reactant: O=S(=O)(O)O
Agent: [Ni+2]
Agent: O=S(=O)([O-])[O-]
Solvent: O
Product: [OH-]

Procedure:
The nickel salt precipitate is next redissolved in solution and re-precipitated as a nickel sulfate starter salt of suitable quality for use in making an active positive electrode material. Preferably, the nickel salt precipitate is dissolved in sulfuric acid to form a nickel sulfate solution and then precipitated out with a condensation precipitation step. The sulfuric acid is preferably concentrated sulfuric acid having a concentration range of 50% to 99%. A condensation precipitation step provides superior nickel sulfate in comparison to nickel sulfate without a condensation precipitation step. For example, the nickel carbonate precipitate formed above may be dissolved in sulfuric acid to form a nickel sulfate solution. The sulfuric acid/nickel sulfate solution is then diluted with water. Water is evaporated from the nickel sulfate solution to precipitate a nickel sulfate solid. The nickel sulfate solid is separated from the sulfate solution by any suitable separation process, such as filtration, decantation, etc. The nickel sulfate solid may then be redissolved in water to form aqueous nickel sulfate suitable for use as a nickel hydroxide starter solution.
Reaction SMILES: [BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:18]=1[C:27]1[CH:28]=[CH:29][C:30]([C:33]([NH:35][CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[O:34])=[N:31][CH:32]=1)=O.[I:43][C:44]1[CH:50]=[CH:49][C:47]([NH2:48])=[CH:46][CH:45]=1.CC(O)=O>CCOC(C)=O.ClCCCl>[I:43][C:44]1[CH:50]=[CH:49][C:47]([NH:48][CH2:15][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:19][C:18]=2[C:27]2[CH:28]=[CH:29][C:30]([C:33]([NH:35][CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[O:34])=[N:31][CH:32]=2)=[CH:46][CH:45]=1
Reactant: Nc1ccc(I)cc1
Reactant: CCOC(=O)CCNC(=O)c1ccc(-c2cc(C(F)(F)F)ccc2C=O)cn1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CCOC(=O)CCNC(=O)c1ccc(-c2cc(C(F)(F)F)ccc2CNc2ccc(I)cc2)cn1
Temperature: 25 °C

Procedure:
Solid NaBH(OAc)3 (2.2 g, 10.1 mmol) was added to a DCE solution (22 mL) of ethyl 3-(5-(2-formyl-5-(trifluoromethyl)phenyl)picolinamido)propanoate (2.0 g, 5.1 mmol), 4-iodoaniline (1.2 g, 5.6 mmol), and AcOH (1.2 mL, 20.3 mmol) and the resulting mixture was stirred at room temperature. After 16 h the resulting mixture diluted with EtOAc washed with water and brine, dried (Na2SO4), dry-packed onto silica gel and purified via column chromatography to yield the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][C:19]=1[F:25])(O)[CH2:10][C:11]1[N:15]([CH3:16])[N:14]=[N:13][N:12]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(OCC)C>[F:25][C:19]1[CH:20]=[C:21]([CH3:24])[CH:22]=[CH:23][C:18]=1[C:9]([C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[F:1])=[CH:10][C:11]1[N:15]([CH3:16])[N:14]=[N:13][N:12]=1
Reactant: Cc1ccc(C(O)(Cc2nnnn2C)c2ccc(C)cc2F)c(F)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: Cc1ccc(C(=Cc2nnnn2C)c2ccc(C)cc2F)c(F)c1

Procedure:
A suspension of 1,1-bis(2-fluoro-4-methylphenyl)-2-(1-methyl-1H-tetrazol-5-yl)ethanol (7.3 g, 21.0 mmoles) in toluene (200 mL) with p-toluene sulfonic acid (3 g) and the mixture heated at reflux for 14 hours. After cooling, the mixture was diluted with diethyl ether and extracted with saturated sodium bicarbonate solution and water. The organic layer was dried (MgSO4) and evaporated. The residue was triturated with isopropyl ether to give the title compound; m.p.=58°-60° C.