Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1([C:30]2[N:31]=[CH:32][C:33]3[CH:38]([C:39](O)=O)[CH2:37][CH2:36][C:34]=3N=2)C=NN=N1.FC1C(C#N)=C(C)C([C@@H]2OC[C@@H]3CNCCN3C2)=CC=1.CCN(C(C)C)C(C)C>CN(C=O)C.ClCCl>[NH:31]1[C:30]2[C:34](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:33][CH2:32]1
Reactant: O=C(O)C1CCc2nc(-n3cnnn3)ncc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cc1c([C@H]2CN3CCNC[C@H]3CO2)ccc(F)c1C#N
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: c1ccc2c(c1)CCN2
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
HATU (266 mg, 0.700 mmol) was added to a solution of 2-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-5-carboxylic acid [I-67] (148 mg, 0.637 mmol) in DMF (1 mL). The mixture was stirred at RT for 5 minutes then a solution of 6-fluoro-2-methyl-3-[(3S,9aS)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl]benzonitrile [I-40A] (411 mg, 0.817 mmol), and Hunig's Base (0.70 mL, 4.0 mmol) in dichloromethane (1 mL) was added. The flask was rinsed twice with dichloromethane (0.3 mL). The reaction mixture was stirred at RT for 2 hours then diluted with EtOAc and washed with saturated NaHCO3 solution, water and brine, dried (MgSO4), filtered and the solvent evaporated to afford crude title compound as a mixture of two diastereomers. This crude material was purified by preparative TLC on silica (2000 μm, eluted twice) using CH2Cl2:MeOH 95:5 (B) to afford the title compound 2 GH as a mixture of diastereomers: LC/MS 512 (M+Na), 490 (M+H). The diastereomers were separated by chiral preparative SFC HPLC (ChiralCel IC, 21×250 mm, 60% MeOH:MeCN/CO2, 50 mL/min, 100 bar, 114 mg/mL in MeCN/MeOH, 35° C., 220 nm) to afford the separated aza-indane diastereomers Isomer 2G (faster eluting) and Isomer 2H (slower eluting). Each isomer was dissolved separately in 1 mL dichloromethane and 1 equivalent of 1 M HCl in ether was added. The solvent was evaporated to yield the HCL salt of each diastereomer. Isomer 2G HCL salt: NMR 600 MHz (CD3OD)(mixture amide rotamers) 10.012 (s, 0.5H); 10.007 (s, 0.5H); 8.72 (s, 0.5H); 8.68 (s, 0.5H); 8.00 (br app t, 1H); 7.31 (dt, 1H); 5.11 (t, 1H); 4.60-4.72 (m, 2H); 4.41 (d, 0.5H); 4.09-4.31 (m, 3H); 3.91 (t, 0.5H); 3.88 (dd, 1.5H); 3.31-3.62 (m, 4H); 3.20-3.28 (m, 2.5H); 2.72-2.86 (m, 1H); 2.61 (s, 3H); 2.30-2.37 (m, 0.5H); 2.21-2.27 (m, 0.5H); LC/MS 531 (M+H+CH3CN). Isomer 2H HCl salt: NMR 600 MHz (CD3OD) (mixture amide rotamers) 10.02 (s, 1H); 8.72 (s, 0.6H); 8.69 (s, 0.4H); 8.02 (app t, 0.4H); 7.98 (aap t, 0.6H); 7.28-7.33 (m, 1H); 5.09 (d, 1H); 4.72-4.77 (m, 1H); 4.64 (d, 0.5H); 4.57 (d, 3H); 4.34 (d, 0.5H); 4.28 (d, 0.5H); 4.05-4.20 (m, 2.5H); 3.86 (t, 1H); 3.75 (q, 1H); 3.48-3.63 (m, 2H); 3.26 (t, 1H); 3.23 (t, 1H); 2.74-2.81 (m, 1H); 2.61 (s, 3H); 2.30-2.36 (m, 0.5H); 2.20-2.27 (m, 0.5H); LC/MS 531 (M+H+CH3 CN).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[C:13]([OH:15])=[O:14].S(=O)(=O)(O)O.[CH2:21](O)[CH3:22]>>[CH2:21]([O:14][C:13]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[CH3:1])[NH:9][C:8](=[O:12])[CH2:7][CH2:6]2)=[O:15])[CH3:22]
Reactant: CCO
Reactant: Cc1cc2c(cc1C(=O)O)CCC(=O)N2
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cc2c(cc1C)NC(=O)CC2
Temperature: 25 °C
Yield: 70 %

Procedure:
To the compound (40.0 g, 195 mmol) obtained in step A were added ethanol (600 ml) and concentrated sulfuric acid (60 ml), and the mixture was heated under reflux for 24 hr. After cooling to room temperature, the solution was concentrated under reduced pressure. The obtained oil was diluted with water, and extracted with chloroform. The organic layer was washed with diluted aqueous sodium hydroxide solution, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained solid was recrystallized from ethanol to give the title compound (32.0 g, yield 70%) as a colorless solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH2:10][C:11]([CH3:14])([CH3:13])[N:12]=2)=[C:4]([CH3:15])[CH:3]=1.C([Li])CCC.[C:21]1(=[O:27])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.O>O1CCCC1.CCCCCC>[OH:27][C:21]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[O:9][CH2:10][C:11]([CH3:14])([CH3:13])[N:12]=3)=[C:4]([CH3:15])[CH:3]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=C1CCCCC1
Reactant: Cc1cc(Br)ccc1C1=NC(C)(C)CO1
Agent: [Li]CCCC
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1cc(C2(O)CCCCC2)ccc1C1=NC(C)(C)CO1
Reaction time: 0.5 h

Procedure:
To a solution of 2-(4-bromo-2-methylphenyl)-4,4-dimethyl-2-oxazoline (5 g) in dry tetrahydrofuran (40 ml) is added dropwise a 1.6M solution of n-butyl lithium in n-hexane (14.0 ml) at −70° C. The mixture is stirred at the same temperature for 30 minutes, and thereto is added dropwise cyclohexanone (2.1 ml), and the mixture is stirred for one hour. To the mixture is added water, and the mixture is evaporated to remove the tetrahydrofuran, and then extracted with diethyl ether. The diethyl ether layer is dried over anhydrous magnesium sulfate, evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=100:1→60:1), recrystallized from acetone/n-hexane to give 2-[4-(1-hydroxy-1-cyclohexyl)-2-methylphenyl]-4,4-dimethyl-2-oxazoline (4.29 g) as white powder.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8]2[CH2:9][C:10]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[CH2:11][N:12]=2)[CH:5]=[CH:4][C:3]=1[CH2:25][OH:26].C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>ClCCl>[CH3:34][S:35]([O:26][CH2:25][C:3]1[CH:4]=[CH:5][C:6]([C:8]2[CH2:9][C:10]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:14])([F:15])[F:16])[CH2:11][N:12]=2)=[CH:7][C:2]=1[Br:1])(=[O:37])=[O:36]
Reactant: OCc1ccc(C2=NCC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1Br
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCc1ccc(C2=NCC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1Br
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.2 %

Procedure:
To a solution of {2-bromo-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl]phenyl}methanol (0.95 g) and triethylamine (0.41 g) in dichloromethane was added methanesulfonyl chloride (0.35 g) gradually, and the mixture was stirred for 2 hours at room temperature. The reaction liquor was washed with water and a saturated aqueous brine, subsequently dried over magnesium sulfate. After filtering the reaction mixture, the solvent was distilled off under reduced pressure, to obtain 2-bromo-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl]-benzyl methanesulfonate (1.0 g).
Reaction SMILES: CC1N=C(N2C(=O)N(CC3C=CC(C(F)(F)F)=CC=3)N=C2)SC=1C(O)=O.[F:27][C:28]1[CH:49]=[CH:48][C:31]([CH2:32][N:33]2[C:37](=[O:38])[N:36]([C:39]3[S:40][C:41]([C:45](O)=[O:46])=[C:42]([CH3:44])[N:43]=3)[CH:35]=[N:34]2)=[CH:30][CH:29]=1.[NH:50]1[CH:54]=[CH:53][C:52]([CH2:55][NH2:56])=[N:51]1>>[NH:50]1[CH:54]=[CH:53][C:52]([CH2:55][NH:56][C:45]([C:41]2[S:40][C:39]([N:36]3[C:37](=[O:38])[N:33]([CH2:32][C:31]4[CH:48]=[CH:49][C:28]([F:27])=[CH:29][CH:30]=4)[N:34]=[CH:35]3)=[N:43][C:42]=2[CH3:44])=[O:46])=[N:51]1
Reactant: Cc1nc(-n2cnn(Cc3ccc(F)cc3)c2=O)sc1C(=O)O
Reactant: NCc1cc[nH]n1
Agent: Cc1nc(-n2cnn(Cc3ccc(C(F)(F)F)cc3)c2=O)sc1C(=O)O
Product: Cc1nc(-n2cnn(Cc3ccc(F)cc3)c2=O)sc1C(=O)NCc1cc[nH]n1
Yield: 49 %

Procedure:
Following the procedure as described in Example 21, making variations as required to replace 4-methyl-2-(5-oxo-1-(4-(trifluoromethyl)benzyl)-1H-1,2,4-triazol-4(5H)-yl)thiazole-5-carboxylic acid with 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid to react with (1H-pyrazol-3-yl)methanamine, the title compound was obtained as a white solid in 49% yield: mp 178-179° C. (ethyl acetate/hexane); 1H NMR (300 MHz, CDCl3) δ 8.23 (s, 1H), 7.59 (br s, 1H), 7.39-7.30 (m, 2H), 7.06-6.96 (m, 2H), 6.88 (t, J=4.7 Hz, 1H), 6.33 (br s, 1H), 6.05 (br s, 1H), 4.95 (s, 2H), 4.64 (d, J=4.7 Hz, 2H), 2.63 (s, 3H); MS (ES+) m/z 414.2 (M+1).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][S:13][CH2:12]2)=[C:4](Cl)[N:3]=1.C(O)CCC.[I:22][C:23]1[CH:24]=[C:25]([CH2:29][NH2:30])[CH:26]=[CH:27][CH:28]=1>C(O)(C)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][S:13][CH2:12]2)=[C:4]([NH:30][CH2:29][C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([I:22])[CH:24]=2)[N:3]=1
Reactant: Clc1nc(Cl)c2ncn(C3CCSC3)c2n1
Reactant: NCc1cccc(I)c1
Solvent: CCCCO
Solvent: CC(C)O
Product: Clc1nc(NCc2cccc(I)c2)c2ncn(C3CCSC3)c2n1
Reaction time: 30 h

Procedure:
The operation is carried out as in Stage 2 of Example 5 starting from 160 mg of the product obtained in Stage 1 of Example 5, 3 ml of butanol and using 0.114 ml of 3-iodo-benzenemethanamine in place of the benzylamine and the reaction medium is taken to a temperature of approximately 80 to 85° C. for approximately 30 hours, left to return to ambient temperature, diluted with 3 ml of isopropanol, placed for approximately one hour at a temperature of approximately 0° C., followed by separating, washing with 5 ml of isopropanol and drying under vacuum to a temperature of approximately 50° C. After purification on silica eluting with methylene chloride/ethyl acetate in a proportion 90/10, 173 mg of expected product is thus obtained in the form of white-yellow crystals.
Reaction SMILES: [CH2:1]([O:8]OC1COC(O)CC1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)[CH:20]([CH3:22])[CH3:21].[C:26]([O:29][C:30](=[O:32])[CH3:31])(=[O:28])[CH3:27]>C(Cl)Cl>[C:26]([O:29][CH:30]1[CH2:31][CH2:22][CH:20]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:21][O:32]1)(=[O:28])[CH3:27]
Reactant: OC1CCC(OOCc2ccccc2)CO1
Reactant: CCN(C(C)C)C(C)C
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Product: CC(=O)OC1CCC(OCc2ccccc2)CO1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 5-(benzyloxy)-2-methoxytetrahydro-2H-pyran (317 mg, 1.426 mmol) in AcOH (10 mL) and water (5 mL) was heated at 55° C. for 12 h and then evaporated to dryness to afford 5-benzyloxyoxytetrahydropyran-2-ol (300 mg). 5-Benzyloxyoxytetrahydropyran-2-ol was dissolved in DCM (3 mL) and treated with DIPEA (0.374 mL, 2.139 mmol) and acetic anhydride (218 mg, 2.139 mmol). The mixture was stirred at rt for 4 h, quenched with sat. NaHCO3 and extracted with DCM. The organic phase was washed with water, brine, dried (MgSO4) and concentrated to yield 5-(benzyloxy)tetrahydro-2H-pyran-2-yl acetate as a clear oil (281 mg).
Reaction SMILES: [C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[C:7]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:10])([CH3:9])[CH3:8]>>[C:7]([C:11]1[CH:16]=[CH:15][C:14]([C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[CH:13][CH:12]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)c1ccccc1
Reactant: CCCC(=O)Cl
Product: CCCC(=O)c1ccc(C(C)(C)C)cc1

Procedure:
The procedure of Example 3 was followed for the reaction of 53g (0.5 mole) of butyryl chloride with 67g (0.5 mole) of tert-butyl benzene. Obtained after high vacuum concentration was 94g of a clear liquid. A VPC analysis indicated a pure product. Ir (film) 3.5 (s), 5.9 (s) microns; nmr (CDCl3) 7.65 (4H, center doublet of doublets), 2.9 (2H, t), 1.75 (2H, sextet), 1.3 (9H, s), 0.95 (3H, t) ppm.
Reaction SMILES: [CH3:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2C2CCCCO2)=[C:4]([C:17]2[C:18]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([NH:30][C:31]([CH:33]4[CH2:35][CH2:34]4)=[O:32])=[CH:26][CH:25]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)[N:3]=1.FC(F)(F)C(O)=O.CO>C(Cl)Cl>[CH3:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([C:17]2[C:18]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([NH:30][C:31]([CH:33]4[CH2:35][CH2:34]4)=[O:32])=[CH:26][CH:25]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)[N:3]=1
Reactant: Cc1nc(-c2cccnc2Nc2ccc(NC(=O)C3CC3)cc2)c2ncn(C3CCCCO3)c2n1
Solvent: ClCCl
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: Cc1nc(-c2cccnc2Nc2ccc(NC(=O)C3CC3)cc2)c2nc[nH]c2n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 30.6 %

Procedure:
A suspension of N-(4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)cyclopropanecarboxamide (80 mg, 0.170 mmol) in DCM (3 mL) was cooled to 0° C. and treated with trifluoroacetic acid (3 mL, 40.4 mmol). The yellow solution was stirred at 0° C. for 1 h. The mixture was concentrated in vacuo, the residue was neutralized with 2 M NH3 in MeOH and then concentrated in vacuo.The crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g) eluting with a gradient of 2% to 10% 2 M NH3.MeOH in DCM to give N-(4-(3-(2-methyl-9H-purin-6-yl)pyridin-2-ylamino)phenyl)cyclopropanecarboxamide (20 mg, 0.052 mmol, 30.5% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 13.47-13.72 (m, 1H); 12.82 (s, 1H); 10.10 (s, 1H); 9.78 (s, 1H); 8.59 (s, 1H); 8.33 (d, J=3.20 Hz, 1H); 7.75 (d, J=76.46 Hz, 2H); 7.58 (d, J=8.53 Hz, 2H); 6.94-7.03 (m, 1H); 2.87 (s, 3H); 1.72-1.82 (m, 1H); 0.72-0.84 (m, 4H). m/z (ESI, +ve ion) 386 (M+H)+.
Reaction SMILES: [CH2:1]([NH:9][CH:10]1[CH2:15][CH2:14][CH:13]([C:16]2[N:17]=[N:18][N:19]3[C:24]=2[C:23]2[CH:25]=[CH:26][NH:27][C:22]=2[N:21]=[CH:20]3)[CH2:12][CH2:11]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1(C2CCC(NC3C=CC(C#N)=CC=3)CC2)N=NN2C=1C1C=CNC=1N=C2>>[CH2:1]([NH:9][C@H:10]1[CH2:15][CH2:14][C@@H:13]([C:16]2[N:17]=[N:18][N:19]3[C:24]=2[C:23]2[CH:25]=[CH:26][NH:27][C:22]=2[N:21]=[CH:20]3)[CH2:12][CH2:11]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:1]([NH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]2[N:17]=[N:18][N:19]3[C:24]=2[C:23]2[CH:25]=[CH:26][NH:27][C:22]=2[N:21]=[CH:20]3)[CH2:12][CH2:11]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: c1ccc(CCNC2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
Agent: N#Cc1ccc(NC2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
Product: c1ccc(CCN[C@H]2CC[C@@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
Product: c1ccc(CCN[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
Yield: 16 %

Procedure:
The reactions in Synthetic Examplea 134 were carried out in substantially the same manners except that N-phenethyl-4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin-1-yl)cyclohexanamine obtained in Synthetic Examplea 123 was used instead of 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin-1-yl)cyclohexyl]amino}benzonitrile to give cis-N-phenethyl-4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin-1-yl)cyclohexanamine (Synthetic Examplea 135a; colorless solid, 3.22 mg, yield 16%) in a less polar fraction and trans-N-phenethyl-4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin-1-yl)cyclohexanamine (Synthetic Examplea 135b; colorless solid, 2.52 mg, yield 11%) in a more polar fraction.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].[CH2:5]1O[CH:6]1[CH3:7].[C:9]1(=[O:16])[O:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1>C1CCCCC1>[CH2:1]=[CH:2][CH:3]=[CH2:4].[CH2:7]=[CH:6][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:9]1(=[O:16])[O:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CC1CO1
Agent: C=CC=C
Agent: O=C1CCCCCO1
Solvent: C1CCCCC1
Product: C=Cc1ccccc1
Reaction time: 0.33 h

Procedure:
Cyclohexane was charged to a 26-oz. beverage bottle equipped with a perforated Crown cap over a self-sealing rubber gasket, and the bottle and cyclohexane were then purged with nitrogen. Styrene and tetrahydrofuran and then the n-butyllithium were added. The temperature was adjusted to 70° C. and the bottle and its contents were tumbled in a constant temperature bath for 20 minutes, after which time the styrene polymerization was essentially complete. 1,3-Butadiene was then charged to the bottle and the polymerization was continued for one hour with continued agitation at 70° C. At the end of this time, polymerization of the butadiene was essentially complete. Propylene oxide was then added to the polymerization reaction mixture and the mixture was agitated for 10 minutes while the temperature was reduced from 70° C. to 30° C. Epsilon-caprolactone was added and polymerization proceeded for 10 minutes with continued agitation. Promptly 10 minutes after the epsilon-caprolactone had been charged, the polymerization reaction was terminated by adding the chosen terminating agent. The reaction mixture and added terminating agent were thoroughly mixed by shaking the beverage bottle to insure quantitative termination of all polymer lithium. One part of 2,6-di-t-butyl-4-methylphenol per hundred parts of total monomer was added as a 10 weight percent solution in 50:50 toluene:isopropanol. The contents of the bottle were emptied into a beaker, and the styrene-butadiene-epsilon-caprolactone block terpolymer was isolated by steam stripping. The recovered polymer was dried at 60° C. for about 15 hours under reduced pressure. Block polycaprolactone was determined for each polymer by an oxidative degradation method as described in Footnote (b) of Table II.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[C:21]([CH2:22][OH:23])=[C:20]([Cl:24])[N:19]=[C:18]3[CH2:25][CH2:26][CH2:27][CH3:28])=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)([OH:3])=[O:2].C[O-].[Na+].[CH3:32][C:33]([CH3:40])([CH3:39])[C:34]([O:36][CH2:37]Cl)=[O:35]>CN(C)C=O>[CH3:32][C:33]([CH3:40])([CH3:39])[C:34]([O:36][CH2:37][O:2][C:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[C:21]([CH2:22][OH:23])=[C:20]([Cl:24])[N:19]=[C:18]3[CH2:25][CH2:26][CH2:27][CH3:28])=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)=[O:3])=[O:35]
Reactant: CC(C)(C)C(=O)OCCl
Reactant: CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2cccc(C(=O)O)c2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2cccc(C(=O)OCOC(=O)C(C)(C)C)c2)cc1
Reaction time: 96 h
Yield: 90 %

Procedure:
To a solution of 1.25 g of 1-[(3'-carboxybiphenyl-4-yl)methyl]-2-butyl-4-chloro-5-hydroxymethylimidazole in 10 mL of dimethylformamide at 25° was added 0.17 g of sodium methoxide followed after 5 minutes by 0.45 g of chloromethyl trimethylacetate. The mixture was stirred at 25° for 4 days. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate. This solution was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography on silica gel afforded 1.38 g of the product as a glassy solid. NMR (200 MHz, CDCl3) δ 7.87 (d, 1H); 7.54 (t, 1H); 7.43 (t, 1H); 7.29 (d, 1H); 7.11 (A2B2, 4H); 5.72 (s, 2H); 5.24 (s, 2H); 4.5 (s, 2H); 2.61 (t, 2H); 2.06 (br s, 1H); 1.68 (quint., 2H); 1.36 (sext., 2H); 1.17 (s, 9H); 0.88 (t, 3H).
Reaction SMILES: [C:1]1([C:7]2[C:16]3[C:11](=[CH:12][C:13]([C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=3)[C:10]([CH3:21])([CH3:20])[CH2:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:22]([C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=1)=O.[OH-].[Na+].Cl>CCO.C1COCC1>[O:19]=[C:17]([C:13]1[CH:14]=[CH:15][C:16]2[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:8][CH2:9][C:10]([CH3:21])([CH3:20])[C:11]=2[CH:12]=1)[CH:18]=[CH:22][C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=1
Reactant: CC(=O)c1ccc2c(c1)C(C)(C)CC=C2c1ccccc1
Reactant: O=Cc1ccc(C(=O)O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CC1(C)CC=C(c2ccccc2)c2ccc(C(=O)C=Cc3ccc(C(=O)O)cc3)cc21
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 115.0 mg (0.42 mmol) of 3,4-dihydro-1-phenyl-4,4-dimethyl-6-acetylnaphthalene (Compound 100H) and 65.0 mg (0.43 mmol) of 4-formyl-benzoic acid in 5.0 ml EtOH and 1.0 ml THF, was added 120.0 mg (3.00 mmol; 3.0 ml of a 1M aqueous solution) of NaOH. The resulting yellow solution was stirred at room temperature for 12 hours. The solution was acidified with 6% aqueous HCl and extracted with EtOAc. The combined organic layers were dried (MgSO4), concentrated under reduced pressure, and the title compounds was isolated by column chromatography (50% EtOAc--hexanes) as a pale yellow solid. 1H NMR (CDCl3): δ 8.13 (2H, d, J=7.7 Hz), 8.04 (1H, s), 7.81 (1H, d, J=15.5 Hz), 7.75 (3H, m), 7.60 (1H, d, J=15.5 Hz), 7.35 (5H, m), 7.14 (1H, d, J=8.1 Hz), 6.15 (1H, t, J=4.2 Hz), 2.41 (2H, d, J=4.2 Hz), 1.41 (6H, s).
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[C:6]([CH3:8])([CH3:7])[O:5][BH:4][O:3]1.Br[C:11]1[CH:16]=[CH:15][C:14]([CH:17]([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:13][CH:12]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(N(CC)CC)C>O1CCOCC1.CC#N.CC#N.Cl[Pd]Cl>[CH3:1][C:2]1([CH3:9])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:13][CH:12]=2)[O:3]1
Reactant: CC1(C)OBOC1(C)C
Reactant: CCOC(=O)C(C)c1ccc(Br)cc1
Agent: Cl[Pd]Cl
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: C1COCCO1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCOC(=O)C(C)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Temperature: 110 °C

Procedure:
4,4,5,5-Tetramethyl-1,3,2-dioxaborolane (1.3 mL, 9.0 mmol) was added to a mixture of ethyl 2-(4-bromophenyl)propanoate (1.3 g, 5.0 mmol), bis(acetonitrile)palladium(II) chloride (26 mg, 0.10 mmol), 2-(dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl (160 mg, 0.40 mmol) and triethylamine (2.1 mL, 15 mmol) in 1,4-dioxane (3.0 mL) and then the mixture was evacuated under reduced pressure and then refilled with nitrogen thrice. The reaction was then heated at 110° C. for 4 h. The mixture was cooled to r.t. and filtered through a short pad of silical gel and then washed with ethyl acetate. The solvent was removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexane (0-10%) to afford the desired product.
Reaction SMILES: Br[C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:11]([Sn](CCCC)(CCCC)C=C)[CH2:12]CC.CN(C)C=O.[F-].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[N+:8]([C:3]1[C:2]([CH:11]=[CH2:12])=[CH:7][CH:6]=[CH:5][N:4]=1)([O-:10])=[O:9]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: O=[N+]([O-])c1ncccc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [F-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=Cc1cccnc1[N+](=O)[O-]
Temperature: 80 °C
Reaction time: 3 h

Procedure:
The mixture of 327 mg of 3-bromo-2-nitropyridine, 256.5 mg of dichlorobis(triphenylphosphine)palladium (II), 518 μL of tributyl(vinyl)tin, and 6 mL of N,N-dimethylformamide, was stirred at 80° C. for 3 hours. The reaction mixture was cooled back to room temperature, then 500 mg of potassium fluoride and 1.5 mL of water were added thereto, and stirred at room temperature for 30 minutes. The insolubles were filtered through celite, a saturated aqueous solution of sodium hydrogen carbonate was added, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The insolubles were filtered, the filtrate was concentrated under reduced pressure, and then the thus obtained residue was purified by silica gel column chromatography, to obtain 236 mg of 2-nitro-3-vinylpyridine [120-1] as a pale red solid.
Reaction SMILES: [OH:1][OH:2].[OH-:3].[Na+].[C:5]1([CH3:20])[CH:10]=[CH:9][C:8]([O:11][C:12]([CH2:14][CH2:15][CH2:16][C:17](Cl)=[O:18])=[O:13])=[CH:7][CH:6]=1.O=O>CCOCC>[C:5]1([CH3:20])[CH:10]=[CH:9][C:8]([O:11][C:12]([CH2:14][CH2:15][CH2:16][C:17]([O:1][O:2][C:17](=[O:18])[CH2:16][CH2:15][CH2:14][C:12]([O:11][C:8]2[CH:7]=[CH:6][C:5]([CH3:20])=[CH:10][CH:9]=2)=[O:3])=[O:18])=[O:13])=[CH:7][CH:6]=1
Reactant: [OH-]
Reactant: OO
Reactant: Cc1ccc(OC(=O)CCCC(=O)Cl)cc1
Agent: O=O
Agent: [Na+]
Solvent: CCOCC
Product: Cc1ccc(OC(=O)CCCC(=O)OOC(=O)CCCC(=O)Oc2ccc(C)cc2)cc1
Reaction time: 3 h
Yield: 61.2 %

Procedure:
To a vigorously stirred solution of 1.7 g. (0.025 mole) of 50% hydrogen peroxide and 22.7 g. (0.057 mole) of aqueous 10% sodium hydroxide at 10°-14° C. was slowly added a solution of 4-(p-tolyloxycarbonyl)-butyryl chloride in 50 ml. of ether. The resulting reaction mixture was stirred for an additional three hours. After a work-up similar to that in Example I 7.5 g. (theory, 10.0 g.) of liquid was obtained. The assay according to "active oxygen" content was 81.5% and the corrected yield was 61.2%. After being stored at 0° C. for several days the product solidifed and had a melting point of 24°-30° C.