Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]([CH3:12])([CH3:11])[C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19]([O-])(=[O:21])=[O:20])=[CH:15][CH:14]=1.[Na+].O>CS(C)=O>[CH:5]1([C:3]([C:2]([S:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:23])=[CH:14][CH:15]=2)(=[O:21])=[O:20])([CH3:12])[CH3:11])=[O:4])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: Cc1ccc(S(=O)(=O)[O-])cc1
Reactant: CC(C)(Cl)C(=O)C1CCCCC1
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: Cc1ccc(S(=O)(=O)C(C)(C)C(=O)C2CCCCC2)cc1
Temperature: 60 °C
Reaction time: 20 h
Yield: 27.4 %

Procedure:
A solution of 2-chloro-1-cyclohexyl-2-methyl-1-propanone (30.0 g, 0.16 mole) and sodium p-toluenesulfonate (30.0 g, 0.17 mole) in dimethylsulfoxide was reacted with stirring at 60° C. for 20 hours. The reaction mixture was poured into cold H2O, and stirred at 0°-5° C. for 1 hour. The precipitate was filtered, washed with H2O and dried. The crude solid (18 g) was recrystallized from n-hexane/benzene to give 13.5 g of 2-cyclohexylcarbonyl-2-(p-toluenesulfonyl)propane as white needles.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[CH:16][C:5]=2[S:6][C:7]=1[C:8]([N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)=[O:9].[Cu][C:25]#[N:26].O>CN(C)C=O>[CH3:21][O:20][C:18]1[C:17]([O:22][CH3:23])=[CH:16][C:5]2[S:6][C:7]([C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:9])=[C:3]([CH3:2])[C:4]=2[C:19]=1[C:25]#[N:26]
Reactant: N#C[Cu]
Reactant: COc1cc2sc(C(=O)N3CCOCC3)c(CBr)c2cc1OC
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2sc(C(=O)N3CCOCC3)c(C)c2c(C#N)c1OC

Procedure:
(4-Bromo-5,6-dimethoxy-3-methyl-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (0.42 g) from Example 33 and copper(I) cyanide (2.0 g) in N,N-dimethylformamide (8 ml) were irradiated in a microwave oven at 150° C. for 1.5 hours. To the mixture water was added and the product was extracted into ethyl acetate. Ethyl acetate was dried and evaporated to dryness.
Reaction SMILES: N[C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][S:8][C:4]=2[CH:3]=1.N([O-])=[O:12].[Na+].[OH-].[Na+]>O.OS(O)(=O)=O>[S:8]1[C:4]2[CH:3]=[C:2]([OH:12])[CH:10]=[CH:9][C:5]=2[N:6]=[CH:7]1
Reactant: Nc1ccc2ncsc2c1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Oc1ccc2ncsc2c1
Temperature: 160 °C
Reaction time: 0.25 h

Procedure:
To a solution of 6-aminobenzothiazole (1.0 g, 6.66 mmol) in water (22 mL) and H2SO4 (16 mL) at 5° C. was added a solution of sodium nitrite (460 mg, 6.72 mmol) in water (13 mL) keeping the temperature below 5° C. The resulting solution was allowed to stir for 15 minutes. The reaction mixture was heated to 160° C. and a solution of H2SO4 (50 mL) and water (38 mL) was slowly added. The resulting mixture was allowed to stir for 1 h. The mixture was allowed to cool and an aqueous solution of 50% sodium hydroxide was added until the pH=7. The mixture was extracted with ethyl acetate and washed with brine. The combined organic was dried over MgSO4 and evaporated to yield a semi-solid. The semi-solid was purified by column chromatography (40% ethyl acetate/hexanes) to yield benzothiazo-6-ol 16 as an off-white solid.
Reaction SMILES: [OH-].[Na+].C(O[C:6]([C:8](C)([C:17](=[O:19])[CH3:18])[CH2:9][CH2:10][CH2:11][CH2:12][S:13]([OH:16])(=[O:15])=[O:14])=O)C>O.CO>[CH3:6][CH:8]([C:17](=[O:19])[CH3:18])[CH2:9][CH2:10][CH2:11][CH2:12][S:13]([OH:16])(=[O:14])=[O:15]
Reactant: CCOC(=O)C(C)(CCCCS(=O)(=O)O)C(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(=O)C(C)CCCCS(=O)(=O)O
Temperature: 50 °C
Reaction time: 15 h

Procedure:
A solution of 290 mg of NaOH in 3 ml water was added to the mixture of 710 mg (2.53 mmol) of 5-ethyloxycarbonyl-5-methyl-6-oxo-1-heptanesulfonic acid in 15 ml of methanol. The obtained mixture was stirred for 15 hours at 50° C. Methanol was removed by a rotary evaporator, residue was acidified to pH 1 and then solvent was removed until dry to yield 5-methyl-6-oxo-1-heptanesulfonic acid. The product thus obtained (940 mg, 4.5 mmol), 1.02 g (5.4 mmol) of 4-hydrazinobenzenesulfonic acid, and 15 ml of acetic acid was refluxing for 16 hours. The insoluble precipitate was filtered and the filtrate was evaporated. The obtained residue was column purified (RP-18, water) to yield 840 mg of the 2,3-dimethyl-3-(4-sulfobutyl)-3H-5-indolesulfonic acid (IVd). δH (200 MHz, DMSO-d6): 7.66 (1H, s, arom H), 7.6 (1H, d, 8.0 Hz, arom H), 7.4 (1H, d, 7.8 Hz arom H), 2.66 (2H, t, 6.8 Hz, CH2SO3H), 2.32 (3H, s, 2-CH3), 2.10-1.78 (2H, m, CH2), 1.53-1.26 (2H, m, CH2), 1.31 (3H, s, 3-CH3), 0.83-0.41 (2H, m, CH2).
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH:16]=O)=[CH:14][N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH:25]1[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:18]1([N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH2:16][N:25]3[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]3)=[CH:14][N:15]=2)=[O:9])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1
Reactant: O=C1CCNCC1
Reactant: O=Cc1cnc(NC(=O)N(C2CCCCC2)C2CCCCC2)s1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Product: O=C1CCN(Cc2cnc(NC(=O)N(C3CCCCC3)C3CCCCC3)s2)CC1
Yield: 11.9 %

Procedure:
Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (34 mg. 0.10 mmol), 4-piperidone hydrochloride (46 mg, 0.30 mmol) and sodium triacetoxyborohydride (25 mg, 0.12 mmol) to afford 5 mg (12%) of the desired product after purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[C:4]([F:11])[CH:3]=1.[Cl:12][C:13]1[C:14]([F:21])=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH:16]=O.C[O-].[Na+]>CO>[Cl:12][C:13]1[C:14]([F:21])=[C:15](/[CH:16]=[C:8](/[C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[F:11])\[C:9]#[N:10])[CH:18]=[CH:19][CH:20]=1
Reactant: N#CCc1ccc(Cl)cc1F
Reactant: O=Cc1cccc(Cl)c1F
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: N#C/C(=C\c1cccc(Cl)c1F)c1ccc(Cl)cc1F
Temperature: 45 °C
Reaction time: 5 h
Yield: 86 %

Procedure:
To a solution of 4-chloro-2-fluorophenylacetonitrile (Matrix) (5 g, 30 mmol) and 3-chloro-2-fluorobenzaldehyde (Oakwood) (5 g, 32 mmol) in methanol (200 mL) was slowly added a methanolic solution (Aldrich, 25 wt. %) of sodium methoxide (21 mL, 92 mmol). The reaction mixture was heated and stirred at 45° C. for 5 h. The mixture was cooled to room temperature and filtered. The white precipitate was washed with water, cold methanol, and then dried under reduced pressure to afford (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile as a white powder (8 g, 86%).
Reaction SMILES: [Br-].[CH2:2]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH:3]=[CH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CC([O-])(C)C.[K+].[Br:36][C:37]1[CH:38]=[C:39]([C:50]2[CH:57]=[CH:56][C:53]([CH:54]=O)=[CH:52][CH:51]=2)[S:40][C:41]=1[C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1.O>C1COCC1>[Br:36][C:37]1[CH:38]=[C:39]([C:50]2[CH:51]=[CH:52][C:53](/[CH:54]=[CH:2]/[CH:3]=[CH:4]/[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)=[CH:56][CH:57]=2)[S:40][C:41]=1[C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1
Reactant: COc1ccc(-c2sc(-c3ccc(C=O)cc3)cc2Br)cc1
Reactant: C(=Cc1ccccc1)C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(-c2sc(-c3ccc(/C=C/C=C/c4ccccc4)cc3)cc2Br)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 74 %

Procedure:
10.83 g (23.6 mmol) of Cinnamyltriphenylphosphonium bromide was added to 2.70 g (24.10 mmol) of t-BuOK in 100 mL THF and the resulting solution was stirred at RT for 30 min. The reaction mixture was cooled to 0° C. and 8 g (21.4 mmol) of the aldehyde (62) was added in 35 mL THF. The solution was warmed to RT and stirred for 5 hrs. The solution was poured into 200 mL water. The precipitated product was separated by filtration to give 7.5 g (74% yield) of pure target molecule.
Reaction SMILES: [BH4-].[Li+].C([O:5][C:6](=O)[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17][C:15]3=2)[CH:10]=[CH:9]1)C.O>C1COCC1>[OH:5][CH2:6][CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17][C:15]3=2)[CH:10]=[CH:9]1
Reactant: CCOC(=O)Cn1ccc2ccc3c(c21)CCN(C(=O)OC(C)(C)C)CC3
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCc2ccc3ccn(CCO)c3c2CC1
Temperature: -10 °C
Reaction time: 2 h
Yield: 111.8 %

Procedure:
Under N2, a flame-dried, 100-mL, three-necked flask was charged with lithium borohydride (0.39 g, 17.0 mmol) and anhydrous THF (10 mL) and cooled to −10° C. A solution of tert-butyl 1-(2-ethoxy-2-oxoethyl)-6,7,9,10-tetrahydroazepino[4,5-g]indole-8(1H)-carboxylate (2.11 g, 5.66 mmol) in anhydrous THF (20 mL) was added and the mixture was allowed to warm to room temperature and was stirred for 2 hours. An additional equivalent of lithium borohydride (0.13 mL, 5.66 mmol) was added and the mixture was stirred at room temperature for 16 hours. Water was added slowly and the mixture was partitioned between EtOAc and water. The combined organic layers were concentrated to give 2.09 g of an oil. Column chromatography (elution with 10–30% Et2O/hexane) gave 1.70 g (91%) of the title compound as a clear oil. An analytical sample was crystallized from EtOAc hexane to give a white solid: mp 109–111° C.; 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J=8 Hz, 1 H), 7.03 (d, J=3 Hz, 1 H), 6.90 (d, J=8 Hz, 1 H), 6.45 (d, J=3 Hz, 1 H), 4.45 (t, J=5 Hz, 2 H), 3.99–3.88 (m, 2 H), 3.72–3.54 (m, 4 H), 3.39–3.25 (m, 2 H), 3.10–2.99 (m, 2 H), 1.38 (s, 9 H); IR (diffuse reflectance) 3470, 2976, 1666, 1457, 1428, 1369, 1350, 1312, 1267, 1251, 1192, 1178, 1081, 816, 720 cm−1; MS (EI) m/z 330 (M+); Anal. Calcd for C19H26N2O3: C, 69.06; H, 7.93; N, 8.48. Found: C, 68.92; H, 7.94; N, 8.43.
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22]O)=[C:18]([O:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:17]=1>>[CH2:25]([O:24][C:18]1[CH:17]=[C:16]([Cl:15])[CH:21]=[CH:20][C:19]=1[CH2:22][O:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1)[CH2:26][CH2:27][CH3:28]
Reactant: CCCCOc1cc(Cl)ccc1CO
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Product: CCCCOc1cc(Cl)ccc1COc1ccnn1-c1cc(C#N)ccn1

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (4-chloro-2-butoxyphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 0.95 (3H, t, J=7.2 Hz), 1.41-1.48 (2H, m), 1.74-1.79 (2H, m), 4.01 (2H, t, J=6.4 Hz), 5.23 (2H, s), 5.77 (1H, d, J=1.6 Hz), 6.90 (1H, d, J=2.0 Hz), 6.95 (1H, dd, J=1.6 Hz, 7.6 Hz), 7.34 (1H, d, J=8.0 Hz), 7.39 (1H, dd, J=0.8 Hz, 4.8 Hz), 7.57 (1H, d, J=1.6 Hz), 8.04 (1H, s), 8.70 (1H, d, J=4.8 Hz). [M+H] Calc'd for C20H19ClN4O2, 383. Found, 383.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[C:5]([CH3:12])[N:4]=1.CO[CH:15](OC)[N:16]([CH3:18])[CH3:17].C(N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[C:5]([CH:12]=[CH:15][N:16]([CH3:18])[CH3:17])[N:4]=1
Reactant: COc1ccc([N+](=O)[O-])c(C)n1
Reactant: COC(OC)N(C)C
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1ccc([N+](=O)[O-])c(C=CN(C)C)n1
Temperature: 120 °C
Yield: 99.6 %

Procedure:
To 2-methoxy-5-nitro-6-methylpyridine (29.39 g, 175 mmol) dissolved in 300 mL of N,N-dimethylformamide was added dimethylformamide dimethylacetal (120 mL, 896 mmol) and triethylamine (1 mL). The bright red reaction mixture was heated at 120° C. for 2 hours, then concentrated in vacuo to provide 38.90 g of the title compound as a red solid, which was used in Preparation 13 without further purification.
Reaction SMILES: C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[CH:11]2.[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.CCO.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:17][C:18]1[CH:23]=[C:22]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13][CH:12]=[CH:11]3)[CH:21]=[CH:20][CH:19]=1
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: OB(O)c1cccc(Cl)c1
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: O
Solvent: CCO
Product: Clc1cccc(-c2ccc3[nH]ccc3c2)c1
Yield: 100.5 %

Procedure:
A stirred slurry of 4.23 g (40 mmol) Na2CO3, 1.84 g (9.4 mmol) 5-bromoindole, 1.88 g (10 mmol) 3-chlorophenylboronic acid, and 0.29 g (0.25 mmol) Pd(PPh3)4 in 50 mL 1:1 EtOH-water was heated to reflux for 2.5 hours. The reaction mixture was allowed to cool and was then poured into 400 mL water and extracted with EtOAc. The organic layer was separated, dried over MgSO4, and concentrated to afford 2.15 g crude 5-(3-chlorophenyl)indole as a tan solid.
Reaction SMILES: [CH2:1]([S:9][CH2:10][CH2:11][OH:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].N1C=CC=CC=1.[C:19](Cl)(=[O:23])[C:20]([CH3:22])=[CH2:21]>C1C=CC=CC=1>[C:19]([O:12][CH2:11][CH2:10][S:9][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])(=[O:23])[C:20]([CH3:22])=[CH2:21]
Reactant: CCCCCCCCSCCO
Reactant: C=C(C)C(=O)Cl
Solvent: c1ccccc1
Solvent: c1ccncc1
Product: C=C(C)C(=O)OCCSCCCCCCCC
Temperature: 5 °C
Reaction time: 3 h
Yield: 66.4 %

Procedure:
2(n-Octylthio)ethanol (13.10 grams, 0.0688 mole) and anhydrous pyridine (65.5 grams) were charged to a three-necked flask fitted with a condenser protected with a drying tube, dropping funnel, thermometer and magnetic stirrer. The solution was cooled to 5° C., and methacrylyl chloride (7.20 grams, 0.0688 mole) was then added dropwise over a 26-minute period. The reaction solution was maintained at 9°-11° C. throughout the addition period, and then at 25° C. for another three hours with stirring. The reaction mixture was then diluted with 150 ml of benzene, and the pyridine hydrochloride present was removed by filtration. The filtrate was washed twice with dilute hydrochloric acid, then with water until neutral and finally dried over anhydrous sodium sulfate. The benzene solvent was stripped off leaving 13.1 grams of crude product which was purified by vacuum distillation to yield 11.8 grams of the desired ester with a boiling point of 111°-124° C./0.07 mm in a yield of 66%.
Reaction SMILES: C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1.[B:17](OC)([O:20]C)[O:18]C.Cl>CCOCC.O>[CH3:14][Si:13]([CH3:16])([CH3:15])[C:9]1[CH:8]=[C:7]([B:17]([OH:20])[OH:18])[CH:12]=[CH:11][CH:10]=1
Reactant: C[Si](C)(C)c1cccc(Br)c1
Reactant: COB(OC)OC
Agent: Cl
Agent: [Li]C(C)(C)C
Solvent: O
Solvent: CCOCC
Product: C[Si](C)(C)c1cccc(B(O)O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86.4 %

Procedure:
t-Butyllithium (28 cm3, 1.7 M in pentane) was added to a solution of (21) (9.65 g, 42 mmol) in ether (200 cm3) cooled in a dry ice/acetone bath, and the reaction was stirred for 30 minutes. Trimethyl borate (20 cm3, 170 mmol) was added, and the reaction was stirred for 16 hours, gradually warming to room temperature. Aqueous hydrochloric acid (3 M, 20 cm3) was added, and the reaction was stirred for a further 2 hours. Water (200 cm3) was added, and the layers were separated. The aqueous layer was extracted with ether (3×30 cm3). The combined organic extracts were washed with brine (300 cm3) and dried over magnesium sulfate, and the solvent was removed to leave a white solid. The crude product was passed through a plug of silica using light petroleum then ether as the eluent. The ether band was collected, and the solvent was removed to leave (22) as a brown solid (7.04 g, 86%).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([C:17](O)=[O:18])[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[CH3:24][NH:25][CH:26]([CH2:28][CH3:29])[CH3:27]>N1C=CC=CC=1>[CH3:24][N:25]([CH:26]([CH3:27])[CH2:28][CH3:29])[C:17]([C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:16]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]=1)=[O:18]
Reactant: CCC(C)NC
Reactant: O=C(O)c1cc(-c2ccccc2)cc2ccccc12
Solvent: c1ccncc1
Solvent: O=S(Cl)Cl
Product: CCC(C)N(C)C(=O)c1cc(-c2ccccc2)cc2ccccc12

Procedure:
The procedure of Example 20 is followed using 3-phenylnaphthalene-1-carboxylic acid (4.3 g), thionyl chloride (20 ml) and N-methylbut-2-ylamine (1.5 g) in pyridine (20 ml) as the starting materials. After recrystallisation from petroleum ether, N-methyl-N-(1-methylpropyl)-3-phenylnaphthalene-1-carboxamide (2.8 g), melting at 125° C., is obtained.
Reaction SMILES: [C:1]1([C:7]2[N:16]=[C:15](Cl)[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>C(O)(C)C>[C:1]1([C:7]2[N:16]=[C:15]([N:27]3[CH2:28][CH2:29][N:24]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=4)[CH2:25][CH2:26]3)[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Clc1nc(-c2ccccc2)nc2ccccc12
Reactant: c1ccc(N2CCNCC2)nc1
Solvent: CC(C)O
Product: c1ccc(-c2nc(N3CCN(c4ccccn4)CC3)c3ccccc3n2)cc1
Temperature: 25 °C

Procedure:
A mixture containing 9.6 g (0.04 mole) of 2-phenyl-4-chloroquinazoline, 6.4 g. (0.04 mole) of 1-(2-pyridyl) piperazine and 250 ml of isopropanol was refluxed for 4 hrs. The resulting reaction mixture was filtered after cooling to room temperature. The crystalline solid was dissolved in 400 ml of 3 N hydrochloric acid and the aqueous acidic liquid was washed with ether. The aqueous layer was adjusted to pH=7.5 which precipitated crystalline solid. This acidification and basification were repeated once. Yield of product was 6.8 g, m.p. 164°-166° C. (air dried).
Reaction SMILES: [C:1]([NH:6][C:7]1[NH:16][C:15](=[O:17])[C:14]2[C:9](=[N:10][CH:11]=[C:12]([CH:18]=O)[N:13]=2)[N:8]=1)(=[O:5])[CH:2]([CH3:4])[CH3:3].[NH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CO>[C:1]([NH:6][C:7]1[NH:16][C:15](=[O:17])[C:14]2[C:9](=[N:10][CH:11]=[C:12]([N:13]=2)[CH2:18][NH:20][C:21]2[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=2)[N:8]=1)(=[O:5])[CH:2]([CH3:3])[CH3:4]
Reactant: Nc1ccc(C(=O)O)cc1
Reactant: CC(C)C(=O)Nc1nc2ncc(C=O)nc2c(=O)[nH]1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CO
Product: CC(C)C(=O)Nc1nc2ncc(CNc3ccc(C(=O)O)cc3)nc2c(=O)[nH]1
Reaction time: 0.17 h

Procedure:
N2-iBu-6-formylpterin (25) 4.0 gm, 15 mmole) was suspended in MeOH. To this suspension was added 4-aminobenzoic acid (2.1 g, 15 mmole) followed by stirring for 10 minutes. The reaction mixture was then cooled in an ice bath with continuous stirring. A solution of pyridinium para-toluene sulfonate (PPTS, 1 M in MeOH, 15 ml, 15 mmol) was added in one portion, followed by the addition of pyridine-borane complex (1.9 ml of 8M solution, 15 mmol) dropwise over a period of 10 minutes. The ice bath was removed, and stirring was continued at room temperature for 3 hours. The fine precipitated product was collected by centrifugation and washed with a 1:1 mixture of hexanes-MeOH several times, and finally with MeOH. The product was dried in vacuum over P2O5 for 24 hours to give light cream-colored powder, yield=5.3 gm, 91%. 1H NMR (DMSO): δ 8.87 (s, 1H), 4.62 (s, 2H), 2.75-2.82 (m, 1H), 1.13, 1.16 (2s, 6H); MS, m/z, M−H+=383 for C18H18N6O4.
Reaction SMILES: Br[C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([OH:16])=[O:15])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1.[CH2:21]([O:23][C:24]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)=[O:25])[CH3:22]>>[CH2:21]([O:23][C:24]([C:26]1[CH:31]=[C:30]([C:2]2[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=2[CH2:4][N:5]2[C:13]3[C:8](=[CH:9][C:10]([C:14]([OH:16])=[O:15])=[CH:11][CH:12]=3)[CH:7]=[CH:6]2)[CH:29]=[CH:28][CH:27]=1)=[O:25])[CH3:22]
Reactant: CCOC(=O)c1cccc(B(O)O)c1
Reactant: O=C(O)c1ccc2c(ccn2Cc2ccccc2Br)c1
Product: CCOC(=O)c1cccc(-c2ccccc2Cn2ccc3cc(C(=O)O)ccc32)c1

Procedure:
The title compound was prepared following the same protocol as described in Step 5, Example 38, using 1-(2-bromobenzyl)-1H-indole-5-carboxylic acid instead of the (S)-1-(4-bromobenzyl)-N-(1-(4-nitrophenyl)ethyl)-1H-indole-5-carboxamide and the (3-(ethoxycarbonyl)phenyl)boronic acid instead of the phenylboronic acid. ESI-MS (m/z): 400 [M+H]+.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1([NH:14][C:15]2[C:16](=[O:35])[N:17]([C:21]3[C:22]([CH3:34])=[CH:23][C:24]([F:33])=[C:25]([CH:32]=3)[C:26]([NH:28][CH:29]3[CH2:31][CH2:30]3)=[O:27])[CH:18]=[CH:19][N:20]=2)[CH2:13][CH2:12]1.[CH3:36][NH2:37].[I-].[K+]>O.O1CCOCC1>[CH:29]1([NH:28][C:26](=[O:27])[C:25]2[CH:32]=[C:21]([N:17]3[CH:18]=[CH:19][N:20]=[C:15]([NH:14][C:11]4([C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3][CH2:2][NH:37][CH3:36])[CH2:13][CH2:12]4)[C:16]3=[O:35])[C:22]([CH3:34])=[CH:23][C:24]=2[F:33])[CH2:31][CH2:30]1
Reactant: CN
Reactant: Cc1cc(F)c(C(=O)NC2CC2)cc1-n1ccnc(NC2(c3ccccc3OCCCl)CC2)c1=O
Agent: [I-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CNCCOc1ccccc1C1(Nc2nccn(-c3cc(C(=O)NC4CC4)c(F)cc3C)c2=O)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5-[3-({1-[2-(2-chloroethoxy)phenyl]cyclopropyl}amino)-2-oxopyrazin-1(2H)-yl]-N-cyclopropyl-2-fluoro-4-methylbenzamide (Example 318h, 100 mg) and methylamine, 40% by wt solution in water (0.1 mL) in dioxane (1 mL) was added potassium iodide (33.4 mg). The reaction mixture was stirred at room temperature overnight, then heated at 40° C. overnight. The reaction was heated at 50° C. for 48 h. Purification by preparative HPLC (Phenomenex Gemini, eluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia, followed by Xbridge column eluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia) gave the title compound as a solid (17 mg).
Reaction SMILES: [CH3:1][Si:2]([CH3:9])([CH3:8])[NH:3][Si](C)(C)C.[S:10]1([C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:14](=[O:15])N1)(=[O:12])=[O:11].N.S(=O)(=O)(O)O>O.C(#N)C>[CH3:1][Si:2]([N:3]1[C:14](=[O:15])[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:10]1(=[O:12])=[O:11])([CH3:9])[CH3:8]
Reactant: C[Si](C)(C)N[Si](C)(C)C
Reactant: O=C1NS(=O)(=O)c2ccccc21
Agent: N
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC#N
Product: C[Si](C)(C)N1C(=O)c2ccccc2S1(=O)=O
Yield: 102 %

Procedure:
2 ml (9.6 mmoles) of hexamethyldisilazane were added to a refluxing mixture of 1.83 mg (10 mmoles) of saccharin, 10 mg (0.02 mmole) of di-4-nitrophenyl N-(4-toluenesulfonyl)-phosphoramidate and 20 ml of acetonitrile under dry nitrogen and the ammonia evolved was led into water by the nitrogen stream and was titrated with 1 N sulfuric acid. The calculated amount of ammonia was evolved within 0.5 hour and the solvent and other volatile materials were removed by evaporation in a rotating film evaporator. Then, the residue was dried under vacuum to obtain 2.50 g (98%) of trimethylsilylsaccharin melting at 90°-92° C.