Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:23][CH2:22]3)[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:30].[Na+].O1CCCC1>CO.C(#N)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:30])[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:23][CH2:22]3)[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: [BH3-]C#N
Reactant: CC(=O)c1cc(Cl)c2cccnc2c1N1CCN(C2CC2)CC1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC#N
Solvent: CO
Product: CC(N)c1cc(Cl)c2cccnc2c1N1CCN(C2CC2)CC1
Temperature: 65 °C

Procedure:
A mixture of 1-[5-chloro-8-(4-cyclopropylpiperazin-1-yl)quinolin-7-yl]ethanone (0.0611 g, 0.185 mmol) and ammonium acetate (0.143 g, 1.85 mmol) in methanol (0.8 mL) and acetonitrile (0.8 mL) was heated at 65° C. in a sealed tube for 1 hour. After cooling to room temperature, to the resulting mixture was added 1.0 M sodium cyanoborohydride in tetrahydrofuran (0.46 mL, 0.46 mmol). The reaction was heated at 65° C. overnight. The mixture was cooled to room temperature, quenched with sat. NaHCO3 solution and extracted with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated to give the desired product. LCMS calculated for C18H24ClN4 (M+H)+: m/z=331.2; Found: 331.1.
Reaction SMILES: [NH2:1][C:2]1[C:6]2[C:7](=[O:25])[N:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[CH:9]=[C:10]([C:11]3[CH:12]=[C:13]([CH:16]=O)[S:14][CH:15]=3)[C:5]=2[NH:4][N:3]=1.[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(#N)C>[NH2:1][C:2]1[C:6]2[C:7](=[O:25])[N:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[CH:9]=[C:10]([C:11]3[CH:12]=[C:13]([CH2:16][N:26]4[CH2:30][CH2:29][CH2:28][CH2:27]4)[S:14][CH:15]=3)[C:5]=2[NH:4][N:3]=1
Reactant: C1CCNC1
Reactant: Nc1n[nH]c2c(-c3csc(C=O)c3)cn(-c3ccccc3Cl)c(=O)c12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: Nc1n[nH]c2c(-c3csc(CN4CCCC4)c3)cn(-c3ccccc3Cl)c(=O)c12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 4-(3-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-7-yl)thiophene-2-carbaldehyde obtained in Step A (100 mg) and pyrrolidine (0.053 mL) in acetonitrile (10 mL) was added sodium triacetoxyborohydride (89 mg) at room temperature, and the mixture was stirred at room temperature 3 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (basic silica gel, methanol/ethyl acetate) to give the title compound (63.1 mg).
Reaction SMILES: Br[C:2]1[C:10]2[O:9][C:8]([C:11]3[CH:19]=[CH:18][C:14]([C:15]([O-:17])=[O:16])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=[C:4]([C:20]#[N:21])[CH:3]=1.[C:22]1(C)[CH:27]=CC=C[CH:23]=1.[C:29](=O)([O-])[O-].[Na+].[Na+].C(B(O)O)(C)=C>C(O)C.O>[C:20]([C:4]1[CH:3]=[C:2]([C:22]([CH3:27])=[CH2:23])[C:10]2[O:9][C:8]([C:11]3[CH:19]=[CH:18][C:14]([C:15]([O:17][CH3:29])=[O:16])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=1)#[N:21]
Reactant: N#Cc1cc(Br)c2oc(-c3ccc(C(=O)[O-])cc3)nc2c1
Reactant: Cc1ccccc1
Reactant: O=C([O-])[O-]
Agent: C=C(C)B(O)O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: C=C(C)c1cc(C#N)cc2nc(-c3ccc(C(=O)OC)cc3)oc12
Temperature: 91 °C
Reaction time: 8 h

Procedure:
To a 5-L, 3-neck round-bottom flask fitted with a stirring paddle, a condenser blanketed with nitrogen, and a thermocouple, was added 4-(7-bromo-5-cyano-1,3-benzoxazol-2-yl)benzoate (55.5 g, INTERMEDIATE 1) toluene (2 L), water (375 ml), ethanol (150 ml), 2M aqueous sodium carbonate (250 ml), and isopropenylboronic acid (83.4 g, INTERMEDIATE 3). The mixture was purged with nitrogen three times and then tetrakis(triphenylphosphine)palladium(0) (9.1 g) was added, and the mixture was purged three times with nitrogen. The mixture was heated to reflux (91° C.) and stirred at this temperature overnight. The mixture was then cooled to 20° C. and the product was filtered, washed with water, dried, and transferred to a 3-L round-bottom flask and rinsed with toluene (1 L). Residual solvent was removed in vacuo. Mass spectrum (ESI) 319.1 (M+1).
Reaction SMILES: [CH3:1][NH:2][C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[NH:5][CH:6]=[N:7]2.C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:20]=1[CH2:21]Cl>CN(C)C(=O)C>[Cl:18][C:19]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:20]=1[CH2:21][N:7]1[CH:6]=[N:5][C:4]2[C:8]1=[N:9][CH:10]=[N:11][C:3]=2[NH:2][CH3:1]
Reactant: Fc1cccc(Cl)c1CCl
Reactant: CNc1ncnc2nc[nH]c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CNc1ncnc2c1ncn2Cc1c(F)cccc1Cl
Yield: 54.8 %

Procedure:
To a mixture of 6-methylaminopurine (298 mg, 2 mmols), potassium carbonate (276 mg, 2 mmols) and N,N-dimethylacetamide (10 ml) was added 2-chloro-6-fluorobenzyl chloride (718 mg, 4 mmols), and the resultant mixture was allowed to react at 110° C. for 8 hours with stirring. The reaction product was then treated in the same manner as Example 12 to give 9-(2-chloro-6-fluorobenzyl)-6-methylaminopurine as needles (320 mg, yield 55%), m.p. 188°-190° C.
Reaction SMILES: Br.Br[CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)=O.[C:12]1([CH2:18][CH2:19][NH:20][C:21]([NH2:23])=[S:22])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])(=O)C.[Na+].C(O)C>O>[C:12]1([CH2:18][CH2:19][NH:20][C:21]2[S:22][CH:3]=[C:4]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=3)[N:23]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: NC(=S)NCCc1ccccc1
Reactant: O=C(CBr)c1ccccn1
Agent: Br
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: c1ccc(CCNc2nc(-c3ccccn3)cs2)cc1
Yield: 67.6 %

Procedure:
A mixture of 2-bromo-1-pyridin-2-ylethanone hydrobromide (4.00 g), N-(2-phenylethyl)thiourea (3.60 g), sodium acetate (1.60 g) and ethanol (30 mL) was stirred with heating under reflux for 1 hr. After cooling, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9-2:1 in volume ratio) to give the title compound (2.71 g, yield 48%) as a yellow oil.
Reaction SMILES: C(OC(=O)[NH:10][CH:11]1[C:25](=[O:26])[N:24]([CH3:27])[CH2:23][C:14]2[C:15]3[CH:16]=[N:17][NH:18][C:19]=3[C:20]([CH3:22])=[CH:21][C:13]=2[CH2:12]1)C1C=CC=CC=1.[H][H].C(Cl)(Cl)[Cl:32]>CO.[Pd]>[ClH:32].[NH2:10][CH:11]1[C:25](=[O:26])[N:24]([CH3:27])[CH2:23][C:14]2[C:15]3[CH:16]=[N:17][NH:18][C:19]=3[C:20]([CH3:22])=[CH:21][C:13]=2[CH2:12]1
Reactant: ClC(Cl)Cl
Reactant: Cc1cc2c(c3cn[nH]c13)CN(C)C(=O)C(NC(=O)OCc1ccccc1)C2
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: Cc1cc2c(c3cn[nH]c13)CN(C)C(=O)C(N)C2
Product: Cl
Reaction time: 3 h

Procedure:
To a solution of (4,9-dimethyl-8-oxo-3,6,7,8,9,10-hexahydro-2,3,9-triaza-cyclohepta[e]inden-7-yl)-carbamic acid benzyl ester (50 mg, 0.132 mmol) in methanol and chloroform (0.5 mL) was added 10% palladium on carbon (20 mg) under nitrogen atmosphere. The reaction mixture was brought to hydrogen atmosphere (1 atm) and stirred for 3 h. The catalyst was filtered and the solvent was evaporated to give 7-amino-4,9-dimethyl-6,7,9,10-tetrahydro-3H-2,3,9-triaza-cyclohepta[e]inden-8-one, hydrochloride in almost quantitative yield. To the amine salt in dichloromethane was added disuccinimidyl carbonate (37 mg, 0.145 mmol) and triethylamine (0.11 mL, 0.8 mmol) at room temperature. After 120 min, 3-piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one, hydrochloride (39 mg, 0.145 mmol) was added and stirring continued for 12 h. The solvent was evaporated and the crude product was purified by Prep HPLC to give 4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid (4,9-dimethyl-8-oxo-3,6,7,8,9,10-hexahydro-2,3,9-triaza-cyclohepta[e]inden-7-yl)-amide in 59% overall yield. MS (ESI) 502 (M+H); Rf=1.31.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[C:13]3[C:14]([O:18][CH2:19][C:20]4([CH2:25][OH:26])[CH2:24][CH2:23][CH2:22][CH2:21]4)=[CH:15][CH:16]=[CH:17][C:12]=3[O:11][N:10]=2)[CH2:3][CH2:2]1.[CH:27]([C:29]1([C:35]([O:37][CH3:38])=[O:36])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=O.C(C1(C(OC)=O)CCC1)=O>>[OH:26][CH2:25][C:20]1([CH2:19][O:18][C:14]2[C:13]3[C:9]([O:8][CH2:7][CH:4]4[CH2:5][CH2:6][N:1]([CH2:27][C:29]5([C:35]([O:37][CH3:38])=[O:36])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:2][CH2:3]4)=[N:10][O:11][C:12]=3[CH:17]=[CH:16][CH:15]=2)[CH2:21][CH2:22][CH2:23][CH2:24]1
Reactant: COC(=O)C1(C=O)CCOCC1
Reactant: OCC1(COc2cccc3onc(OCC4CCNCC4)c23)CCCC1
Agent: COC(=O)C1(C=O)CCC1
Product: COC(=O)C1(CN2CCC(COc3noc4cccc(OCC5(CO)CCCC5)c34)CC2)CCOCC1

Procedure:
The title compound was prepared according to the procedure described in Step 3 of EXAMPLE 2 using [1-({[3-(Piperidin-4-ylmethoxy)-1,2-benzisoxazol-4-yl]oxy}methyl)cyclopentyl]methanol (EXAMPLE 51, Step 4) and methyl 4-formyltetrahydro-2H-pyran-4-carboxylate (EXAMPLE 18, Step 1) instead of 3-(piperidin-4-ylmethoxy)-4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazole and methyl 1-formylcyclobutane-carboxylate.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH:15]=[CH:14][N:13]=[CH:12][C:11]=3[N:10]=[CH:9]2)=[N:6][CH:7]=1.[Cl:17][C:18]1[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21].[CH3:31][Mg+].[Br-]>C1COCC1.CCOCC>[Cl:17][C:18]1[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][C:19]=1[C:20]([N:13]1[CH:14]=[CH:15][C:16]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=3)[CH:9]=[N:10][C:11]=2[CH:12]1[CH3:31])=[O:21]
Reactant: Fc1ccc(-n2cnc3cnccc32)nc1
Reactant: C[Mg+]
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1Cl
Agent: [Br-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC1c2ncn(-c3ccc(F)cn3)c2C=CN1C(=O)c1cccc(C(F)(F)F)c1Cl
Temperature: -78 °C
Reaction time: 1 h
Yield: 54 %

Procedure:
To a solution of Intermediate 1 (0.70 g, 3.27 mmol) in THF (20 mL) was added Intermediate 12 (0.87 g, 3.60 mmol) dropwise. The reaction was allowed to stir for 1 h then cooled to −78° C. To the cooled solution was added 3M MeMgBr in Et2O (1.31 mL, 3.92 mmoL) and the reaction was let come to room temperature. The mixture was then quenched with 1N NaOH (50 mL) and extracted with EtOAc (3×30 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the resulting residue (SiO2; MeOH (NH3):DCM) gave the title compound (770 mg, 54%). 1H NMR (400 MHz, CDCl3) δ 8.43-8.34 (m, 1H), 7.92-7.73 (m, 2H), 7.70-7.33 (m, 4H), 6.08 (dtd, J=19.7, 11.7, 8.0 Hz, 3H), 1.54 (t, J=7.0 Hz, 3H). MS (ESI): mass calculated for C20H13ClF4N4O, 436.07. m/z found 437.1 [M+H]+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([OH:24])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](Cl)(=[O:29])[C:26](Cl)=O.FC(F)(F)C(O)=O.[NH2:38][CH2:39][C:40]1C=[CH:46][C:45]([F:48])=[CH:44][C:41]=1C#N.C(N(CC)C(C)C)C>C(Cl)Cl.CN(C)C=O>[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([N:38]1[CH2:39][C:40]2[C:26](=[CH:46][C:45]([F:48])=[CH:44][CH:41]=2)[C:25]1=[O:29])=[O:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1(C)OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
Reactant: O=C(Cl)C(=O)Cl
Reactant: N#Cc1cc(F)ccc1CN
Agent: CCN(CC)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC1(C)OCCn2c1nc(C(=O)N1Cc3ccc(F)cc3C1=O)c(OCc1ccccc1)c2=O
Reaction time: 0.5 h
Yield: 14 %

Procedure:
To a stirred suspension of intermediate 27, 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido-[2,1-c][1,4]oxazine-2-carboxylic acid, (1.65 g, 5 mmol) in CH2Cl2 (15 mL) was added a catalytic amount of dimethylformamide and 10 mL of a 2 M oxalylchloride in CH2Cl2. After 30 min., the resulting clear yellow solution was concentrated to afford a light brown solid. This solid was dissolved in CH2Cl2 (50 mL) and added to a stirred mixture of intermediate 107, 2-(aminomethyl)-5-fluorobenzonitrile trifluoroacetic acid salt, (1.77 g, 5.97 mmol) and diethylisopropylamine (2.6 mL, 15 mmol) in CH2Cl2 (100 mL). After 1 h, the clear brown reaction mixture was concentrated and the resulting residue dissolved in ethyl acetate (200 mL) then washed sequentially with water (25 mL), 1N HCl (25 mL), water (25 mL) and brine (25 mL). The combined aqueous layers were extracted with CH2Cl2 (3×50 mL). The combined organic phases were dried (Na2SO4), filtered, concentrated and purified by flash chromatography (SiO2), using 30–50% ethyl acetate/Hexanes as eluent to afford the title compound (0.331 g, 14% yield) as a yellow powder. 1H NMR (500 MHz, CDCl3) δ: 7.48–7.45 (1H, m), 7.88 (2H, d, J=7.9 Hz), 7.30 (2H, d, J=7.0 Hz), 7.12 (2H, t, J=7.6 Hz), 7.05–7.01 (1H, m), 5.22 (2H, s), 4.77 (2H, s), 4.06 (4H, s), 1.59 (6H, s). HRMS (M+H) calcd for C25H23FN3O5: 464.1622; found: 464.1628.
Reaction SMILES: N.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[S:11][C:12]([C:16]([O:18]CC)=O)=[C:13]([CH3:15])[N:14]=1.COC1C=CC=CC=1C([NH2:27])=O.ClC(C(C)=O)C(OCC)=O.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S>C(O)C>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[S:11][C:12]([C:16]([NH2:27])=[O:18])=[C:13]([CH3:15])[N:14]=1
Reactant: COc1ccccc1C(N)=O
Reactant: CCOC(=O)c1sc(-c2ccccc2OC)nc1C
Agent: CCOC(=O)C(Cl)C(C)=O
Agent: N
Agent: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: CCO
Product: COc1ccccc1-c1nc(C)c(C(N)=O)s1
Yield: 70 %

Procedure:
Into a solvent mixture of 50 ml of aqueous 28% ammonia and 450 ml of ethanol, 13.9 g of ethyl 2-(2-methoxyphenyl)-4-methylthiazole-5-carboxylate which had been prepared by heating a mixture of o-methoxybenzamide, ethyl α-chloroacetoacetate and phosphorus pentasulfide under a reflux condenser for 5 hours was dissolved. Then in a similar manner as in Example 3 the object was obtained as colourless minute aciculate melting at 191° to 192.5° C. in an amount of 8.7 g corresponding to the yield of 70%.
Reaction SMILES: [H-].[Na+].[C:3]([C:8]1[CH:13]=[C:12]([C:14]([CH2:17][CH3:18])([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=1[OH:19])([CH2:6][CH3:7])([CH3:5])[CH3:4].Br[C:21]1[CH:30]=[CH:29][C:28](OC)=[CH:27][C:22]=1[C:23]([O:25][CH3:26])=[O:24].CCCCCCC.[CH2:40]([O:42][CH2:43]C)C>N1C=CC=CC=1.[Cu]Cl.C(OCC)(=O)C>[C:3]([C:8]1[CH:13]=[C:12]([C:14]([CH2:17][CH3:18])([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=1[O:19][C:21]1[CH:30]=[CH:29][C:28]([CH2:40][O:42][CH3:43])=[CH:27][C:22]=1[C:23]([O:25][CH3:26])=[O:24])([CH2:6][CH3:7])([CH3:5])[CH3:4]
Reactant: COC(=O)c1cc(OC)ccc1Br
Reactant: CCC(C)(C)c1ccc(O)c(C(C)(C)CC)c1
Reactant: CCOCC
Agent: Cl[Cu]
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCC(C)(C)c1ccc(Oc2ccc(COC)cc2C(=O)OC)c(C(C)(C)CC)c1
Yield: 90 %

Procedure:
To a solution of sodium hydride (1.2 g, 0.05 mol) in pyridine (60 mL), was added a solution of 2,4-di-tert-pentylphenol (12.9 g, 0.055 mol) in pyridine (20 mL) with stirring. Gas evolution ceased in approximately 1.5 hr at which time methyl 2-bromo-5-methoxylbenzoate was added. Copper (I) chloride (1.24 g, 0.0126 mol) was added and the mixture heated to reflux for 8 hours. The reaction mixture was diluted with diethyl ether (100 mL) and washed with 3N HCl (3×50 mL) and then washed with saturated sodium bicarbonate (1×50 mL). The organic extracts were dried over sodium sulfate, filtered and concentrated to give a dark oil. Chromatography on silica gel with 1:1 heptane:ethyl acetate yielded the pure product as a viscous oil in 90% yield. NMR and mass spectral analysis were consistent with proposed structure.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:6][C:7]=1[CH3:8].[OH:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:23][O:22][C:20](=[O:21])[C:19]1[CH:24]=[CH:25][C:16]([O:15][CH2:2][C:3]2[N:4]=[C:5]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[O:6][C:7]=2[CH3:8])=[CH:17][CH:18]=1
Reactant: COC(=O)c1ccc(O)cc1
Reactant: Cc1oc(-c2ccccc2)nc1CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OCc2nc(-c3ccccc3)oc2C)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-chloromethyl-5-methyl-2-phenyl-oxazole (3.0 g, 14.4 mmol), methyl 4-hydroxybenzoate (2.64 g, 17.3 mmol), and potassium carbonate (6.0 g, 43.34 mmol) in DMF is stirred at RT overnight. The mixture is then partitioned between EtOAc and water, and the organic phase is washed with brine, dried over magnesium sulfate, and concentrated under vacuum to give the crude product. The material is purified by silica gel chromatography using 15% EtOAc in hexane as the eluent to give 4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy) benzoic acid methyl ester as a white solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.C(N([CH:16]([CH3:18])[CH3:17])CC)(C)C.Cl.C[NH2:21]>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([NH:21][CH2:18][CH2:16][CH3:17])[CH:5]=[C:6]([Cl:8])[N:7]=1
Reactant: CN
Reactant: CCN(C(C)C)C(C)C
Reactant: Clc1cc(Cl)nc(Cl)n1
Agent: Cl
Solvent: C1CCOC1
Product: CCCNc1cc(Cl)nc(Cl)n1
Reaction time: 72 h

Procedure:
A mixture of 2,4,6-trichloropyrimidine (I, 11 g) in THF (160 ml) is cooled to -70°. Diisopropylethylamine (11 ml) is added, followed by the addition of a mixture of n-propylamine (II, 4.9 ml) in THY (15 ml). The mixture is allowed to stand for 3 days at 20°-25° and then is concentrated. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate. The organic extract is washed with water and saline, then dried and concentrated to give a solid. The solid is chromatographed on silica gel (650 g) packed in ethyl acetate/hexane (10/90) and eluted with ethyl acetate/hexane (10→30/90→70). The appropriate fractions (14-18) are pooled and concentrated to give the tire compound, NMR (CDCl3) 6.29, 5.87, 3.21, 1.65 and 0.99δ.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][CH2:8][CH2:7][C:6]2=[N:13][OH:14].O.[CH2:16]([N:18]=[C:19]=[O:20])[CH3:17]>C1C=CC=CC=1.CCOCC>[CH2:16]([NH:18][C:19]([O:14][N:13]=[C:6]1[C:5]2[CH:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:10]=2[O:9][CH2:8][CH2:7]1)=[O:20])[CH3:17]
Reactant: CCN=C=O
Reactant: COc1ccc2c(c1)C(=NO)CCO2
Solvent: CCOCC
Solvent: O
Solvent: c1ccccc1
Product: CCNC(=O)ON=C1CCOc2ccc(OC)cc21
Reaction time: 8 h

Procedure:
A 42 g (0.22 mole) portion of 6-methoxy-4-chromanone oxime in 600 ml of benzene was refluxed until all water was removed via a Dean-Stark trap. The solution was treated with 1 ml of triethylamine, followed by the dropwise addition of 14 g (0.20 mole) of ethyl isocyanate at reflux. The reaction mixture was refluxed for 4 hrs., stored overnight at room temperature, and stripped of benzene under reduced pressure. The viscous residue was taken up in 250 ml of ether, refrigerated 6 hrs., and filtered. The cream colored solid was washed with 150 ml of ether and dried, m.p. 97°-98°. Yield: 44 g (83%).
Reaction SMILES: C(S([NH:7][C@H:8]([C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=1)[CH2:9][S:10][C:11]([CH3:18])([CH3:17])[C:12](OCC)=[O:13])=O)(C)(C)C.Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>CO>[F:26][C:21]1[CH:20]=[C:19]([C@H:8]2[NH:7][C:12](=[O:13])[C:11]([CH3:18])([CH3:17])[S:10][CH2:9]2)[CH:24]=[C:23]([F:25])[CH:22]=1
Reactant: CCOC(=O)C(C)(C)SC[C@H](NS(=O)C(C)(C)C)c1cc(F)cc(F)c1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: CO
Product: CC1(C)SC[C@@H](c2cc(F)cc(F)c2)NC1=O
Temperature: 115 °C

Procedure:
To a solution of methyl 2-{[(2R)-2-[(tert-butylsulfinyl)amino]-2-(3,5-difluorophenyl)ethyl]thio}-2-methylpropanoate from Step C (428 mg, 1.09 mmol) in MeOH (20 mL), cooled to 0° C., was added anhydrous HCl gas for 1 minute. The reaction was sealed and allowed to sit at 0° C. for fifteen minutes, after which nitrogen was bubbled through the reaction for twenty minutes. The reaction was concentrated in vacuo. Additional MeOH (30 mL) was added and it was again concentrated in vacuo. This was repeated with another addition of MeOH and triethylamine (440. mg, 4.35 mmol). To the resulting residue was added toluene (10 mL) and triethylamine (440. mg, 4.35 mmol). A reflux condenser was attached and the mixture stirred at 115° C. After one week of stirring, the reaction was judged to be 90% complete by LCMS. The mixture was cooled to ambient temperature and concentrated in vacuo. The residue was diluted with diethyl ether (50 mL) and washed individually with 20 mL of each of the following aqueous solutions: 1 M HCl (twice), water, and saturated brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to give a residue that was purified by silica gel chromatography, eluting with a gradient of MeOH:CH2Cl2—1:99 to 5:95, to give the title compound. MS: m/z=258 (M+1).
Reaction SMILES: FC(F)(F)S(O)(=O)=O.[Cl:9][CH:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([CH3:20])[C:12]2[C:21]3[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=3[O:23][C:11]1=2.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([SH:35])=[CH:31][CH:30]=1>C(OCCO)C.CCCCCC>[Cl-:9].[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([S:35][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N+:13]([CH3:20])=[C:12]3[C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[O:23][C:11]=23)=[CH:31][CH:30]=1
Reactant: CN1c2ccccc2C(Cl)c2oc3ccccc3c21
Reactant: Sc1ccc(Cl)cc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: CCOCCO
Solvent: CCCCCC
Product: C[n+]1c2ccccc2c(Sc2ccc(Cl)cc2)c2oc3ccccc3c21
Product: [Cl-]
Temperature: 25 °C
Reaction time: 0.1 h
Yield: 77.7 %

Procedure:
To a solution 11-chloro-5-methylbenzofuro[3, 2-b]quinoline trifluoromethanesulfonate from Example 56 (65 mg, 0.156 mmol) in 2-ethoxyethanol (5 ml) was added 4-chlorothiophenol (23 mg, 0.156 mmol) causing the reaction mixture to became a bright yellow. After 5-7 min, TLC showed the disappearance of the starting material. The reaction mixture was cooled to room temperature, diluted with hexane (100 mL), cooled below room temperature, filtered and dried to afford 50 mg (63%) of the title compound, mp 150°-151° C.; 1H NMR (CDCl3) δ 8.71 (d, 1H, J=7.6), 8.60 (s, 2H), 8.23 (s, 1H), 7.96 (s, 1H), 7.86 (t, 1H, J=6.8), 7.64 (m, 2H), 7.44-7.37 (m, 4H), 5.06 (s, 3H); 13C NMR (CDCl3) δ 159.65, 146.54, 140.91, 139.53, 137.16, 136.95, 136.13, 135.33, 135.10, 130.24, 129.26, 127.46, 126.74, 126.65, 126,48, 126.08, 119.23, 116.29, 113.54, 41.25; MS (FAB, m/z) 376 (M+).
Reaction SMILES: [CH3:1][O:2][P:3]([O:7]C)([O:5][CH3:6])=[O:4].[CH2:9]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[CH3:10]>[Ta]>[CH3:1][O:2][P:3]([O-:7])([O:5][CH3:6])=[O:4].[CH3:1][N+:11]([CH2:14][CH3:15])([CH2:12][CH3:13])[CH2:9][CH3:10]
Reactant: CCN(CC)CC
Reactant: COP(=O)(OC)OC
Agent: [Ta]
Product: CC[N+](C)(CC)CC
Product: COP(=O)([O-])OC

Procedure:
This example shows the usefulness of this type of electrolyte system for tantalum foil. Methyltriethylammonium dimethylphosphate was prepared by reaction of 70.8 g. of trimethylphosphate and 50.5 g. of triethylamine in 50 ml. of acetonitrile and then removing the acetonitrile. The resistivity was 1020 Ω-cm. A 36% solution of this material is N,N-dimethylformamide had a resistivity of 85 ohm-cm, and the maximum formation voltage for tantalum foil at 25° C. was 145 V.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:17]([O:19][CH2:20][CH3:21])=[O:18]>ClC(Cl)Cl>[OH:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:2][CH2:3]1
Reactant: CCOC(=O)Cl
Reactant: OCC1CCNCC1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCOC(=O)N1CCC(CO)CC1
Reaction time: 2 h
Yield: 70 %

Procedure:
To a stirred mixture of 67 parts of 4-piperidinemethanol, 61 parts of N,N-diethylethanamine and 750 parts of trichloromethane there were added dropwise 64.5 parts of ethyl chloroformate. Stirring was continued for 2 hours at reflux temperature. After cooling, the reaction mixture was washed with water, dried, filtered and evaporated, yielding 75 parts (70%) of ethyl 4-(hydroxymethyl)-1-piperidinecarboxylate (interm. 50).