Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[C:6]([N:8]1[CH2:25][CH2:24][C:11]2([N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:14]([CH3:22])[NH:13][C:12]2=[O:23])[CH2:10][CH2:9]1)=[O:7].[N:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1>>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[C:6]([N:8]1[CH2:9][CH2:10][C:11]2([N:15]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:14]([CH3:22])[N:13]([C:38]3[CH:39]=[CH:40][N:35]=[CH:36][CH:37]=3)[C:12]2=[O:23])[CH2:24][CH2:25]1)=[O:7]
Reactant: CC1NC(=O)C2(CCN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CC2)N1c1ccccc1
Reactant: OB(O)c1ccncc1
Product: CC1N(c2ccncc2)C(=O)C2(CCN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CC2)N1c1ccccc1

Procedure:
The title compound, MS: m/e=563.2 (M+H+), was prepared in accordance with the general method of example 63 from (rac)-8-(3,5-bis-trifluoromethyl-benzoyl)-2-methyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one and pyridine-4-boronic acid.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][N:11]([C:13](=[O:21])[C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH2:10][C:9](=[O:22])[N:8]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]([N:32]4[CH2:36][CH:35]=[CH:34][CH2:33]4)=[O:31])=[CH:26][CH:25]=3)[C:7]=2[CH:37]=1.C(N(CC)CC)C.[CH3:45][S:46](Cl)(=[O:48])=[O:47]>ClCCl>[CH3:45][S:46]([O:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][N:11]([C:13](=[O:21])[C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[CH2:10][C:9](=[O:22])[N:8]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]([N:32]4[CH2:36][CH:35]=[CH:34][CH2:33]4)=[O:31])=[CH:26][CH:25]=3)[C:7]=2[CH:37]=1)(=[O:48])=[O:47]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(c1ccc(CN2C(=O)CN(C(=O)c3ccc(Cl)cc3)Cc3ccc(CO)cc32)cc1)N1CC=CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCc1ccc2c(c1)N(Cc1ccc(C(=O)N3CC=CC3)cc1)C(=O)CN(C(=O)c1ccc(Cl)cc1)C2
Reaction time: 2 h

Procedure:
450 mg (0.87 mmol) of 8-hydroxymethyl-1-[4-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benzyl]-4-(4-chlorobenzoyl)-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on was dissolved in 5 ml of dichloromethane. 0.18 ml (1.31 mmol) of triethylamine and 0.08 1 ml (1.05 mmol) of methanesulfonyl chloride were added to the obtained solution under cooling with ice, and the obtained mixture was stirred for 2 hours. After the treatment with dichloromethane as the extracting solvent by an ordinary method, the crude product was obtained.
Reaction SMILES: C(OC([NH:8][C:9]1[C:10](=[O:29])[O:11][C:12]2[CH:25]=[C:24]3[CH2:26][CH2:27][CH2:28][C:23]3=[CH:22][C:13]=2[C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:8][C:9]1[C:10](=[O:29])[O:11][C:12]2[CH:25]=[C:24]3[CH2:26][CH2:27][CH2:28][C:23]3=[CH:22][C:13]=2[C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21]
Reactant: Cc1ccccc1-c1c(NC(=O)OC(C)(C)C)c(=O)oc2cc3c(cc12)CCC3
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccccc1-c1c(N)c(=O)oc2cc3c(cc12)CCC3
Yield: 98.3 %

Procedure:
To a solution of 3-tert-butyloxycarbonylamino-4-(2-methylphenyl)-7,8-dihydro-6H-cyclopenta[g][1]benzopyran-2-one (2.05 g) in dichloromethane (20 ml) was added trifluoroacetic acid (10 ml) dropwise with ice-cooling. The mixture was stirred under ice-cooling for 1 hour, after which the solvent was distilled off. The residue was diluted with water, neutralized with saturated aqueous solution of NaHCO3 and extracted with chloroform. The extract was washed with water and dried (MgSO4) and the solvent was distilled off to give crystals of 3-amino-4-(2-methylphenyl)-7,8-dihydro-6H-cyclopenta[g][1]-benzopyran-2-one (1.5 g, 98.4%). Recrystallization from ethanol-dichloromethane gave colorless prisms, m.p. 275°-276° C.
Reaction SMILES: [NH2:1][C:2]1[CH:24]=[C:23]([C:25]#[N:26])[CH:22]=[CH:21][C:3]=1[CH2:4][C:5]([O:18][CH2:19][CH3:20])([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=1[F:17])[C:6]([NH2:8])=[O:7].[CH2:27]([S:34](Cl)(=[O:36])=[O:35])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[C:25]([C:23]1[CH:22]=[CH:21][C:3]([CH2:4][C:5]([O:18][CH2:19][CH3:20])([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[F:17])[C:6]([NH2:8])=[O:7])=[C:2]([NH:1][S:34]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:36])=[O:35])[CH:24]=1)#[N:26]
Reactant: O=S(=O)(Cl)Cc1ccccc1
Reactant: CCOC(Cc1ccc(C#N)cc1N)(C(N)=O)c1ccc(OC)cc1F
Product: CCOC(Cc1ccc(C#N)cc1NS(=O)(=O)Cc1ccccc1)(C(N)=O)c1ccc(OC)cc1F

Procedure:
In analogy to example 95.4, (RS)-(2-amino-4-cyano-benzyl)-2-ethoxy-2-(2-fluoro-4-methoxy-phenyl)-acetamide (example 322.4) was reacted with benzyl sulfonylchloride to give (RS)-(4-cyano-2-phenylmethanesulfonylamino-benzyl)-2-ethoxy-2-(2-fluoro-4-methoxy-phenyl)-acetamide. Off-white foam. MS 512.3 ([M+H]+)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]([OH:14])=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].S(Cl)([Cl:17])=O>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]([Cl:17])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(CC(=O)O)cc1OC
Solvent: c1ccccc1
Product: COc1ccc(CC(=O)Cl)cc1OC
Temperature: 50 °C

Procedure:
To a solution of 20 g. (0.10 mole) of 3,4-dimethoxyphenylacetic acid in 100 ml. of benzene was added dropwise 70 ml. (115 g., 0.98 mole) of thionyl chloride. The solution was heated to 50° C. for two hours, then evaporated in vacuo to give a residue of 3,4-dimethoxyphenylacetyl chloride. A solution of 21.4 g. (0.10 mole) of the acid chloride in 70 ml. of chloroform was added with stirring to a solution of 70 ml. of chloroform and 22.2 ml. (30.0 g., 0.30 mole) of N,N-di-(n-propyl)amine at 0° C. The resulting mixture was heated at 50° C. for two hours, cooled, diluted and washed with dilute hydrochloric acid, dilute sodium carbonate solution and water. The dried chloroform solution was evaporated in vacuo to give N,N-di(n-propyl)-3,4-dimethoxyphenylacetamide.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17](=O)[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[CH:14][CH:15]=3)[O:10][CH:9]=2)=[CH:4][CH:3]=1.O.[NH2:21][NH2:22]>C(O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([C:16]3[CH:15]=[CH:14][C:13]([OH:19])=[CH:12][C:11]=3[OH:10])=[N:21][NH:22][CH:9]=2)=[CH:4][CH:3]=1
Reactant: O=c1c(-c2ccc(Br)cc2)coc2cc(O)ccc12
Reactant: NN
Solvent: CCO
Solvent: O
Product: Oc1ccc(-c2n[nH]cc2-c2ccc(Br)cc2)c(O)c1

Procedure:
This compounds was synthesised in the same manner as described in the preceding experiment. 3-(4-Bromo-phenyl)-7-hydroxy-chromen-4-one (0.1 g, 0.3 mmol), hydrazine hydrate (4 ml), ethanol (10 ml). The crude solid product was washed in hot ether to give 4-[4-(4-Bromo-phenyl)-1H-pyrazol-3-yl]-benzene-1,3-diol as a white solid (0.069, 60.6%); Rf 0.44 Cf SM 0.79 ethyl acetate/hexane (75/25).
Reaction SMILES: Cl([O-])(=O)(=O)=O.Cl[C:7]1[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9](=[N+:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:8]=1.[CH2:20]([S:32]([CH2:35][C:36]#[N:37])(=[O:34])=[O:33])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C(N(CC)CC)C>C(O)C>[CH3:13][C:11]1([CH3:14])[CH2:10][C:9]([N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:8][C:7](=[C:35]([S:32]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])(=[O:34])=[O:33])[C:36]#[N:37])[CH2:12]1
Reactant: CC1(C)CC(Cl)=CC(=[N+]2CCCC2)C1
Reactant: CCCCCCCCCCCCS(=O)(=O)CC#N
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCS(=O)(=O)C(C#N)=C1C=C(N2CCCC2)CC(C)(C)C1

Procedure:
N-(3-Chloro-5,5-dimethylcyclohex-2-en-1-ylidene)-pyrrolidinium perchlorate (3.2 g.), dodecylsulfonylacetonitrile (2.7 g.) and triethylamine (3.1 ml.) are dissolved in ethanol (15 ml.) and heated at reflux for 5 minutes. After chilling, the solid is collected on a filter, washed with methanol and dried. Obtaining pure dye by recrystallization from methanol proved difficult. The product is eluted from basic alumina, using a 10% methanol-90% chloroform solvent mixture, and then recrystallized from methanol. The yield of purified dye is 0.5 g. (11%), m.p. 114°-115°C. This dye compound shows good ultraviolet absorption characteristics as indicated in the data in Table 1 below.
Reaction SMILES: [Se](=O)=O.C([O:8]O)(C)(C)C.[CH3:10][C:11]1([CH3:30])[CH2:20][CH2:19][C:18]([CH3:22])([CH3:21])[C:17]2[CH:16]=[C:15]([C:23]([CH3:25])=[CH2:24])[C:14]([O:26][CH2:27][CH2:28][CH3:29])=[CH:13][C:12]1=2.CCCCCC>ClCCl>[CH3:10][C:11]1([CH3:30])[CH2:20][CH2:19][C:18]([CH3:21])([CH3:22])[C:17]2[CH:16]=[C:15]([C:23]([CH3:25])=[CH:24][OH:8])[C:14]([O:26][CH2:27][CH2:28][CH3:29])=[CH:13][C:12]1=2
Reactant: C=C(C)c1cc2c(cc1OCCC)C(C)(C)CCC2(C)C
Reactant: CC(C)(C)OO
Agent: O=[Se]=O
Solvent: ClCCl
Solvent: CCCCCC
Product: CCCOc1cc2c(cc1C(C)=CO)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 38.5 %

Procedure:
Into a 5 mL round-bottom flask was introduced selenium dioxide (71 mg, 0.64 mmol), 1 mL of dichloromethane, and 90% t-butyl hydroperoxide (0.284 mL, 2.56 mmol). After the mixture had been stirred for 30 min. at room temperature, 2-(5,5,8,8-tetramethyl-3-propyloxy-5,6,7,8-tetrahydronaphthalen-2-yl)-propene (366 mg, 1.28 mmol), in 1 mL of dichloromethane was slowly added. The mixture was stirred at room temperature for 3 h. Then quenched with aqueous saturated NaHCO3. The mixture was extracted with dichloromethane (2×10 mL), washed with water (10 mL) and brine (10 mL), and the combined organic phase dried (Na2SO4). Concentrated in vacuo to give an oil which was subjected to chromatography (10% EtOAC/90% hexane) to give 149 mg (40%) of 2-(5,5,8,8-tetramethyl-3-propyloxy-5,6,7,8-tetrahydro naphthalen-2-yl)-propen-1-ol. 1H NMR (400 MHz, (CDCl3) δ 7.14(s, 1H, aromatic), 6.76(s, 1H, aromatic), 5.36(s, 1H, vinylic), 5.22(s, 1H, vinylic), 4.44(d, J=6.1 Hz, CH2OH), 3.93(t, J=6.5 Hz, 2H, CH2), 2.19(t, J=6.1 Hz, 1H, OH), 1.82(sx, J=6.8 Hz, 2H, CH2), 1.66(s, 4H, 2CH2), 1.28(s, 6H, 2CH3), 1.26(s, 3H, CH3), 1.25(s, 3H, CH3) and 1.03(t, J=7.3 Hz, 3H, CH3).
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].C(N(CC)CC)C.[P:16](Cl)(Cl)([O:18][CH2:19][CH2:20][CH2:21][CH3:22])=[O:17]>CCOCC>[P:16]1([O:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:1]=2[O:2]1)([O:18][CH2:19][CH2:20][CH2:21][CH3:22])=[O:17]
Reactant: Oc1ccccc1O
Reactant: CCCCOP(=O)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CCCCOP1(=O)Oc2ccccc2O1
Yield: 93 %

Procedure:
Pyrocatechol (0.993 g, 9.02 mM) was dissolved in 50 ml of ether and, using 1.825 g (18.04 mM) of triethylamine and 1.723 (9.02 mM) of n-butyl dichlorophosphate, the reaction was carried out at -5° C. to 0° C. and the reaction mixtured treated in the same manner as in Reference Example 1. There was obtained 1.914 g (93.0% yield) of n-butyl o-phenylene phosphate as a colorless viscous oil.
Reaction SMILES: C(OP([CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1)(OCC)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:30][C:31]1([CH3:49])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH:42]=O)[CH:39]=2)[S:34][CH2:33][CH2:32]1>C1COCC1.CCCCCC>[CH3:49][C:31]1([CH3:30])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])/[CH:42]=[CH:9]/[C:10]3[CH:11]=[CH:12][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:18][CH:19]=3)[CH:39]=2)[S:34][CH2:33][CH2:32]1
Reactant: CCOP(=O)(Cc1ccc(C(=O)OC)cc1)OCC
Reactant: CCCCCC(C=O)c1ccc2c(c1)C(C)(C)CCS2
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCCC(/C=C/c1ccc(C(=O)OC)cc1)c1ccc2c(c1)C(C)(C)CCS2
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 39.3 %

Procedure:
0.51 g of methyl 4-(diethoxyphosphorylmethyl)-benzoate were dissolved in 7.5 ml THF and treated, at −20° C., with 1.8 ml of a 1M solution of lithium bis(trimethylsilyl)amide in hexane. After 15 min. at −20° C., a solution of 350 mg of (RS)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanal in 7.5 ml THF was added. The reaction mixture was stirred at room temperature for 1.5 hour. The mixture quenched by the addition of 10 ml of water and the resulting mixture was partitioned in 25 ml ethyl acetate/15 ml sat. aq. sodium chloride solution. The phases were separated and the organic phase was dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by flash chromatography (SiO2, 10% ethyl acetate/hexanes), giving 200 mg of the corresponding ester. 1H NMR (CDCl3): 7.94 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H), 7.19 (d, J=1.8 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.91 (dd, J=8.1, 1.8 Hz, 1H), 6.45 (d, J=15.9 Hz, 1H), 6.38 (d, J=15.9 Hz, 1H), 3.90 (s, 3H), 3.30 (m, 1H), 3.05-3.00 (m, 2H), 2.00-1.90 (m, 2H), 1.85-1.75 (m, 2H), 1.33 (s, 6H), 1.40-1.30 (m, 6H), 0.86 (t, J=6.5 HZ, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17](=O)[C:16]3[C:15]([C:19]([O:21]CC)=O)=[CH:14][CH:13]=[CH:12][C:11]=3[NH:10][CH:9]2[C:24]2[CH:29]=[CH:28][C:27]([CH2:30][N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.O.[NH2:37][NH2:38]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:17]3=[N:37][NH:38][C:19](=[O:21])[C:15]4[CH:14]=[CH:13][CH:12]=[C:11]([C:16]=43)[NH:10][CH:9]2[C:24]2[CH:25]=[CH:26][C:27]([CH2:30][N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])=[CH:28][CH:29]=2)=[CH:6][CH:7]=1
Reactant: NN
Reactant: CCOC(=O)c1cccc2c1C(=O)C(c1ccc(Cl)cc1)C(c1ccc(CN(CC)CC)cc1)N2
Solvent: O
Solvent: CO
Product: CCN(CC)Cc1ccc(C2Nc3cccc4c(=O)[nH]nc(c34)C2c2ccc(Cl)cc2)cc1
Temperature: 23 °C
Reaction time: 8 h
Yield: 37 %

Procedure:
A mixture of ethyl 3-(4-chlorophenyl)-2-(4-((diethylamino)methyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (268 mg) in 85% hydrazine monohydrate (0.5 mL) and methanol (2 mL) was stirred at 23° C. for overnight. Methanol was removed under reduced pressure. The crude was purified by prep-HPLC to give the title compound (93 mg, yield 37%). LC-MS (ESI) m/z: 459 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 0.93 (t, 6H), 2.38 (q, 4H), 3.44 (s, 2H), 4.35 (d, 1H), 4.73 (d, 1H), 7.13-7.19 (m, 5H), 7.22-7.25 (m, 4H), 7.38 (d, 2H), 7.41 (s, 1H), 7.56-7.59 (m, 1H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.[F:15][C:16]([F:26])([F:25])[C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH:20]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(O)(=O)C>[F:15][C:16]([F:25])([F:26])[C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH2:20][N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:5][CH2:6]1
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Reactant: O=Cc1cccc(C(F)(F)F)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: CC(C)(C)OC(=O)NC1CCN(Cc2cccc(C(F)(F)F)c2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl piperidin-4-ylcarbamate (0.15 g, 0.75 mmol) and 3-(trifluoromethyl)benzaldehyde (0.12 mL, 0.156 mmol) in dichloroethane (5 mL) was added sodium triacetoxyborohydride (0.24 g, 1.12 mmol) and a few drops of acetic acid, and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with dichloroethane and washed with saturated aqueous NaHCO3 solution. The organic layer was separated, dried over MgSO4, and chromatographed on silica gel, eluting with 30% ethyl acetate/hexane to yield the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.58 (s, 1H), 7.45 (m, 3H), 4.41 (m, 1H), 3.50 (m, 2H), 3.50 (m, 1H), 2.77 (d, J=12.21 Hz, 2H), 2.11 (t, J=11.70 Hz, 2H), 1.91 (d, J=11.53 Hz, 2H), 1.41 (s, 9H), 1.34 (m, 2H); MS (DCI) m/z 359 (M+H)+.
Reaction SMILES: [CH:1]([Si:3]([CH3:11])([CH3:10])[O:4][Si:5]([CH:8]=[CH2:9])([CH3:7])[CH3:6])=[CH2:2].C(O)(=O)C.[CH3:16][O:17][SiH:18]([O:21][CH3:22])[O:19][CH3:20]>[Pt]>[CH:8]([Si:5]([CH3:7])([CH3:6])[O:4][Si:3]([CH:1]([Si:18]([O:21][CH3:22])([O:19][CH3:20])[O:17][CH3:16])[CH3:2])([CH3:10])[CH3:11])=[CH2:9]
Reactant: CO[SiH](OC)OC
Reactant: C=C[Si](C)(C)O[Si](C)(C)C=C
Agent: [Pt]
Solvent: CC(=O)O
Product: C=C[Si](C)(C)O[Si](C)(C)C(C)[Si](OC)(OC)OC
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A siloxane according to the present invention was prepared by charging a flask with 55.8 g (0.3 mole) of 1,3-divinyl-1,1,3,3-tetramethyldisiloxane under a nitrogen atmosphere. A platinum/vinylsiloxane catalyst, prepared according to the method described by Hitchcock et al.(Angew. Chem. Int. Ed. Engl., 30, 1991) was added at a level of 10−6 equivalent of platinum. Acetic acid (0.06 g; 0.001 mol) was introduced and the reaction mixture heated to 60° C. Trimethoxysilane (12.2 g; 0.1 mol) and 0.24 g (0.004 mol) acetic acid were added to an addition funnel and this mixture was slowly added to the flask while the temperature was maintained below 70° C. Subsequently, the reaction mixture was kept at 70° C. for 1 hr. The product was isolated by fractional distillation at 80° C./8 mm Hg to obtain a mixture (confirmed by NMR) of 7% of an α-adduct (1-vinyl-3-(1-trimethoxysilylethyl)-1,1,3,3-tetramethyldisiloxane) having the structure
Reaction SMILES: [CH2:1]([N:5]1[CH:11]([CH3:12])[CH2:10][C:9]([CH3:14])([CH3:13])[NH:8][C:7]([CH3:16])([CH3:15])[C:6]1=[O:17])[CH2:2][CH2:3][CH3:4].[CH3:18]C(CC)=O>>[CH2:1]([N:5]1[CH:11]([CH3:12])[CH2:10][C:9]([CH3:14])([CH3:13])[NH:8][C:7]([CH2:15][CH3:18])([CH3:16])[C:6]1=[O:17])[CH2:2][CH2:3][CH3:4]
Reactant: CCC(C)=O
Reactant: CCCCN1C(=O)C(C)(C)NC(C)(C)CC1C
Product: CCCCN1C(=O)C(C)(CC)NC(C)(C)CC1C

Procedure:
The title compound was prepared as described by Pyong-nae Son, J. T. Lai.: J. Org. Chem. 46, 323 (1981) for 1-butyl-3,3,5,5,7-pentamethyl-[1,4]diazepan-2-one, but using methylethylketon instead of acetone.
Reaction SMILES: [NH2:1][CH:2]([CH:5]([CH3:7])[CH3:6])[CH2:3][OH:4].[CH3:8][N:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][C:12](=[O:19])[N:11]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][N:26]=[C:25]([C:28](Cl)=[O:29])[C:24]=3[CH:31]=2)[C:10]1=[O:32]>O1CCCC1.C(OCC)C>[CH3:8][N:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][C:12](=[O:19])[N:11]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][N:26]=[C:25]([C:28]([NH:1][CH:2]([CH2:3][OH:4])[CH:5]([CH3:7])[CH3:6])=[O:29])[C:24]=3[CH:31]=2)[C:10]1=[O:32]
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2ccc3snc(C(=O)Cl)c3c2)c1=O
Reactant: CC(C)C(N)CO
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)C(CO)NC(=O)c1nsc2ccc(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)cc12
Yield: 86.2 %

Procedure:
To a solution of 2-amino-3-methyl-1-butanol (1.39 g, 13.5 mmol) in anhydrous tetrahydrofuran at 0° C. is added dropwise a solution of 5-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acid chloride (2.10 g, 5.39 mmol) in tetrahydrofuran. The resultant mixture is stirred 7.5 hours at ambient temperature, diluted with diethyl ether, washed with 1M aqueous hydrochloric acid, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel with hexanes-ethyl acetate to afford the title compound as a solid (2.12 g, 86.2%, mp 120° C.) which is identified by NMR spectral analysis.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([CH2:11][CH:12]3[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]3)[C:4]=2[O:3]1.[C:20]([NH:22][C:23]([NH2:25])=[NH:24])#[N:21]>C(OCCOCCO)C>[NH2:25][C:23]1[N:22]=[C:20]([NH2:21])[C:16]2[CH2:17][CH:12]([CH2:11][C:10]3[C:4]4[O:3][C:2]([CH3:19])([CH3:1])[CH2:6][C:5]=4[CH:7]=[CH:8][CH:9]=3)[CH2:13][CH2:14][C:15]=2[N:24]=1
Reactant: N#CNC(=N)N
Reactant: CC1(C)Cc2cccc(CC3CCC(=O)CC3)c2O1
Solvent: CCOCCOCCO
Product: CC1(C)Cc2cccc(CC3CCc4nc(N)nc(N)c4C3)c2O1

Procedure:
This compound is prepared in a manner analogous to that of Example 1, using 3.4 grams (0.013 mole) of 4-(2,3-dihydro-2,2-dimethylbenzofuran- 7-ylmethyl)cyclohexanone and 1.2 grams (0.014 mole) of cyanoguanidine in 2-(2-ethoxyethoxy)ethanol, yielding 2,4-diamino-6-(2,3-dihydro-2,2-dimethylbenzofuran-7-ylmethyl)-5,6,7,8-tetrahydroquinazoline.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8](B(O)O)=[CH:9][C:4]=2[CH2:3][CH2:2]1.I[C:14]1[C:22]2[C:17](=[N:18][CH:19]=[N:20][C:21]=2[NH2:23])[N:16]([CH:24]([CH3:26])[CH3:25])[N:15]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:14]3[C:22]4[C:17](=[N:18][CH:19]=[N:20][C:21]=4[NH2:23])[N:16]([CH:24]([CH3:26])[CH3:25])[N:15]=3)=[CH:9][C:4]=2[CH2:3][CH2:2]1
Reactant: OB(O)c1ccc2c(c1)CCO2
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: COCCOC
Product: CC(C)n1nc(-c2ccc3c(c2)CCO3)c2c(N)ncnc21
Temperature: 80 °C
Yield: 53.2 %

Procedure:
A solution of 2,3-dihydro-1-benzofuran-5-ylboronic acid (38 mg, 0.23 mmol) in EtOH (1.65 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (30 mg, 0.1 mmol) in DME (6 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (0.95 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA95 (15.7 mg, 59% yield). ESI-MS (M+H)+ m/z calcd 296.1, found 296.1.
Reaction SMILES: BrC1C=CC=C(C)C=1.[Li]CCCC.CCCCCC.COC(NCC[O:27][C@@H:28]([C:42]1[CH:43]=[C:44]([CH3:48])[CH:45]=[CH:46][CH:47]=1)[C@@H:29]1[CH2:34][CH2:33][CH2:32][N:31]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:30]1)=O>C1COCC1>[CH3:48][C:44]1[CH:43]=[C:42]([CH:47]=[CH:46][CH:45]=1)[C:28]([C@@H:29]1[CH2:34][CH2:33][CH2:32][N:31]([C:35]([O:37][C:38]([CH3:41])([CH3:39])[CH3:40])=[O:36])[CH2:30]1)=[O:27]
Reactant: COC(=O)NCCO[C@@H](c1cccc(C)c1)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Agent: Cc1cccc(Br)c1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1cccc(C(=O)[C@@H]2CCCN(C(=O)OC(C)(C)C)C2)c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 125.8 %

Procedure:
To a solution of 1-bromo-3-methylbenzene (88.4 g, 0.52 mol) in anhydrous THF (550 mL) at −78° C. under nitrogen was added dropwise a solution of 2.5 M n-BuLi in hexane (210 mL, 0.52 mol). After stirring for 1 hr at −78° C., a solution of (R)-tert-butyl 3-((R)-(2-(methoxycarbonylamino)ethoxy)(m-tolyl)methyl)piperidine-1-carboxylate (120 g, 0.44 mol) in anhydrous THF (500 mL) was added dropwise. After addition, the reaction mixture was allowed to warm to rt and stirred for 2 hr. The mixture was quenched with saturated NH4Cl solution (500 mL) and extracted with EtOAc (3×400 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give crude (R)-tert-butyl 3-(3-methylbenzoyl)piperidine-1-carboxylate (168 g), which was used immediately for next step without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:13](=[O:22])[C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH2:21])=[CH:16][CH:15]=3)[S:11][C:7]=2[C:6]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[CH:5][CH:4]=1.[CH:29]1([C:33](Cl)=[O:34])[CH2:32][CH2:31][CH2:30]1>>[CH:29]1([C:33]([NH:21][CH2:20][C:17]2[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:10]3[S:11][C:7]4[C:6]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:8]=4[N:9]=3)=[O:22])=[CH:15][CH:16]=2)=[O:34])[CH2:32][CH2:31][CH2:30]1
Reactant: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccc(CN)cc3)nc12
Reactant: O=C(Cl)C1CCC1
Product: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccc(CNC(=O)C4CCC4)cc3)nc12

Procedure:
Using N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-4-aminomethyl-benzamide and cyclobutanecarbonyl chloride, the title compound was prepared as off-white crystals (52% yield). MS: m/e=481(M+H+).