Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[N:9]=[C:8]1[NH:16][CH:17]1[CH2:22][CH2:21][N:20](C(OCC)=O)[CH2:19][CH2:18]1.[OH-].[K+]>O.CC(O)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[N:9]=[C:8]1[NH:16][CH:17]1[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]1
Reactant: CCOC(=O)N1CCC(Nc2nc3cccnc3n2Cc2ccco2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: c1coc(Cn2c(NC3CCNCC3)nc3cccnc32)c1
Yield: 85 %

Procedure:
A mixture of 50 parts of ethyl 4-[[3-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino]-1-piperidinecarboxylate, 50 parts of potassium hydroxide, 400 parts of 2-propanol and 20 drops of water was stirred and refluxed for about 5 hours. The reaction mixture was evaporated and water was added to the residue. The product was extracted twice with 4-methyl-2-pentanone. The combined extracts were dried, filtered and evaporated. The solid residue was stirred in 1,1'-oxybisethane. The product was filtered off and dried, yielding 34 parts (85%) of 3-(2-furanylmethyl)-N-(4-piperidinyl)-3H-imidazo[4,5-b]pyridin-2-amine; mp. 159.0° C. (intermediate 68).
Reaction SMILES: C(C1C=CC(C(NC2C=CC(C3C=C4C(CN([C@@H](C(C)C)C(O)=O)C4=O)=CC=3)=NC=2)=O)=CC=1)(C)(C)C.[C:37]([C:41]1[CH:74]=[CH:73][C:44]([C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([C:54]3[CH:62]=[C:61]4[C:57]([CH2:58][N:59]([C@@H:64]([CH:69]([CH3:71])[CH3:70])[C:65]([O:67]C)=[O:66])[C:60]4=[O:63])=[CH:56][CH:55]=3)=[CH:50][C:49]=2[F:72])=[O:46])=[CH:43][CH:42]=1)([CH3:40])([CH3:39])[CH3:38]>>[C:37]([C:41]1[CH:74]=[CH:73][C:44]([C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([C:54]3[CH:62]=[C:61]4[C:57]([CH2:58][N:59]([C@@H:64]([CH:69]([CH3:70])[CH3:71])[C:65]([OH:67])=[O:66])[C:60]4=[O:63])=[CH:56][CH:55]=3)=[CH:50][C:49]=2[F:72])=[O:46])=[CH:43][CH:42]=1)([CH3:38])([CH3:40])[CH3:39]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccc(C(C)(C)C)cc4)c(F)c3)cc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccc(C(C)(C)C)cc4)cn3)cc2C1=O
Product: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccc(C(C)(C)C)cc4)c(F)c3)cc2C1=O
Yield: 86 %

Procedure:
The compound of example 444 was prepared analogous to the compound of example 404 by hydrolysis of the compound of example 443.
Reaction SMILES: C1CCN(CCOC(C2C=CC(Cl)=CC=2)C2C=CC=CC=2)CC1.Cl.[C:25]([O:29][C:30]([NH:32][C:33]1[S:34][CH:35]=[C:36](/[C:38](=[N:59]/[O:60][C:61]([CH3:70])([CH3:69])[C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])/[C:39]([NH:41][C@@H:42]2[C:45](=[O:46])[NH:44][C@@H:43]2[CH2:47][NH:48][CH2:49][CH2:50][O:51][Si](C(C)(C)C)(C)C)=[O:40])[N:37]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].F.[F-].[NH4+]>CN(C=O)C.CN1C(=O)CCC1.O>[C:25]([O:29][C:30]([NH:32][C:33]1[S:34][CH:35]=[C:36](/[C:38](=[N:59]/[O:60][C:61]([CH3:70])([CH3:69])[C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])/[C:39]([NH:41][C@@H:42]2[C:45](=[O:46])[NH:44][C@@H:43]2[CH2:47][NH:48][CH2:49][CH2:50][OH:51])=[O:40])[N:37]=1)=[O:31])([CH3:27])([CH3:28])[CH3:26]
Reactant: CC(C)(C)OC(=O)Nc1nc(/C(=N/OC(C)(C)C(=O)OC(C)(C)C)C(=O)N[C@@H]2C(=O)N[C@@H]2CNCCO[Si](C)(C)C(C)(C)C)cs1
Agent: Cl
Agent: Clc1ccc(C(OCCN2CCCCC2)c2ccccc2)cc1
Agent: F
Solvent: CN(C)C=O
Solvent: CN1CCCC1=O
Solvent: O
Product: CC(C)(C)OC(=O)Nc1nc(/C(=N/OC(C)(C)C(=O)OC(C)(C)C)C(=O)N[C@@H]2C(=O)N[C@@H]2CNCCO)cs1
Reaction time: 65 h
Yield: 99.5 %

Procedure:
Prepared according to Seki et al. Synlett 1995, 609-611. To a solution of tert-butyl 2-(((Z)-(1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-(((2R,3S)-2-(((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)methyl)-4-oxoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoate (111 mg, 0.162 mmol) in DMF:NMP (2.7:1, 1.62 mL) was added ammonium fluoride hydrofluoride (37.0 mg, 0.648 mmol). After stirring for 65 h, the solution was diluted with water and extracted with EtOAc. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford crude title compound (92 mg, 99%). The crude material was used directly in step 3. LCMS: R=0.76 min, m/z 571.3 (M+1) Method 2m_acidic.
Reaction SMILES: [Br:1][C:2]1[NH:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([O:13]C)=[C:9]([Cl:15])[CH:8]=2)=[N:4][C:3]=1C(F)(F)F.[OH-].[Na+].Br>CC(O)=O>[Br:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[C:9]([Cl:15])[CH:8]=2)[NH:4][CH:3]=1
Reactant: COc1ccc(-c2nc(C(F)(F)F)c(Br)[nH]2)cc1Cl
Agent: Br
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: Oc1ccc(-c2nc(Br)c[nH]2)cc1Cl
Reaction time: 4 h
Yield: 52.2 %

Procedure:
A mixture of 56 (7.4 g, 0.021 mol) and 10% NaOH (200 ml) was heated at reflux with stirring. After 4 hours, the solution was cooled, extracted with CH2Cl2 (2×), acidified with concentrated HCl, cooled and filtered to yield 100% of crude acid. The crude acid (6.9 g, 0.021 mol), AcOH (40 ml) and 48% HBr (160 ml) were heated at reflux with stirring. After 15 hours, the solution was concentrated to dryness and the residue treated with NaHCO3. The mixture was concentrated to dryness and the residue combined with silica gel and chromatographed on silica gel and the product eluted with 5% CH3OH--CHCl3 to yield 3.0 g (53%) of 57, m.p. 225°-27° C. (CH3CN).
Reaction SMILES: [CH2:1]([CH:8]([C:14](OCC)=O)[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].IC[CH2:21][CH2:22][CH2:23][CH2:24][C:25]([F:31])([F:30])[C:26]([F:29])([F:28])[F:27]>>[F:30][C:25]([F:31])([C:26]([F:27])([F:28])[F:29])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:14][CH:8]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7])[C:9]([O:11][CH2:12][CH3:13])=[O:10]
Reactant: FC(F)(F)C(F)(F)CCCCCI
Reactant: C=CCCCCCC(C(=O)OCC)C(=O)OCC
Product: C=CCCCCCC(CCCCCC(F)(F)C(F)(F)F)C(=O)OCC

Procedure:
Starting with the diethyl 2-(6-heptenyl)malonate prepared in Example 9 and the 1-iodo-6,6,7,7,7-pentafluoro-heptane prepared in Example 3, the same procedure as shown in Example 5 was repeated to give ethyl 2-(6,6,7,7,7-pentafluoroheptyl)-8-nonenoate.
Reaction SMILES: [CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][C:18](OCC)=[O:19])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O>CCOCC>[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][OH:19])[CH2:11][CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCCN1CCC(OCc2ccccc2)CC1
Solvent: CCOCC
Solvent: O
Product: OCCCCN1CCC(OCc2ccccc2)CC1
Yield: 83.1 %

Procedure:
The compound obtained from step 1 (4.8 g) was dissolved in ether, and cooled in an ice bath. LialH4 (0.1 g) was added slowly to the solution. The resulting mixture was reacted at room temperature for 1 hr. before adding water to end the reaction. The resulting solution was then extracted by using water and ester. An organic solution layer was dehydrated over magnesium sulfate, filtered, and concentrated under reduced pressure. The column chromatography was performed thereon, thereby obtaining crude yellowish liquid product (3.44 g, 83% yield) of the title.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:13])([CH3:12])[C:4](=[O:14])[C:3]=1C(OCC)=O.Cl>O1CCOCC1.C(OCC)(=O)C.O>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:12])([CH3:13])[C:4](=[O:14])[CH:3]=1
Reactant: CCOC(=O)C1=C(O)c2ccccc2C(C)(C)C1=O
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: CC1(C)C(=O)C=C(O)c2ccccc21
Temperature: 25 °C

Procedure:
A solution of the product of Example 9E (2.25 g, 8.65 mmol) in dioxane (50 mL) was treated with 1 N HCl solution (60 mL) and the mixture was stirred at reflux for 6 hours, cooled to 25° C., diluted with ethyl acetate and water. The organic layer was washed with water (2×) and saturated sodium chloride solution (1×), dried(Na2SO4), filtered and concentrated in vacuo. The residue was triturated with ether and filtered.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:15])=[O:4].Br[CH:17]([CH3:19])[CH3:18].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[N:7]([CH:17]([CH3:19])[CH3:18])[C:6]=1[CH3:15])=[O:4]
Reactant: CC(C)Br
Reactant: COC(=O)c1c(C)[nH]c2cc(Cl)ccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1c(C)n(C(C)C)c2cc(Cl)ccc12
Temperature: 100 °C
Yield: 60.9 %

Procedure:
A mixture of 6-chloro-2-methyl-1H-indole-3-carboxylic acid methyl ester (300 mg, 1.34 mmol), 2-bromopropane (1.75 mL, 18.6 mmol), potassium carbonate (743 mg, 5.37 mmol) and DMF (3.5 mL) is heated to 100° C. for 14 h. The mixture is diluted with water and extracted with ether. The ether layers are washed with water and brine and dried over MgSO4. The residue is purified via flash chromatography eluting with 80% CH2Cl2-heptane to give the title compound (217 mg, 61%) as a white solid. ES/MS m/e 266.0 (M+1).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][C:10]#[N:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+:12]([O-])([OH:14])=[O:13]>>[N+:12]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH2:7][CH2:8][CH2:9][C:10]#[N:11])([O-:14])=[O:13]
Reactant: N#CCCCc1ccccc1
Reactant: O=[N+]([O-])O
Product: N#CCCCc1ccccc1[N+](=O)[O-]
Reaction time: 2 h

Procedure:
4-Phenylbutyronitrile (12.7 g) was added dropwise to stirred concentrated nitric acid (55 ml) at 5°-10° C. and the mixture was stirred for 2 hours at 20°-25° C. The deep yellow solution was poured onto ice and extracted with dichloromethane. The extract was dried and evaporated and the residue was chromatographed on silica in ethyl acetate-hexane (1:4) to isolate the minor product.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:16]1CC[CH2:18][CH2:17]1.C(N(CC)CC)C.C(Cl)(=O)C>O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:17](=[O:16])[CH3:18])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1ccc(OCc2ccccc2)cc1
Reactant: C1CCOC1
Solvent: CC(=O)Cl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)Oc1ccc(OCc2ccccc2)cc1
Reaction time: 24 h

Procedure:
To 35.0 g (175.0 mmol) of 4-(benzyloxy)phenol were added 100 ml of dried tetrahydrofuran and 17.7 g (175.2 mmol) of triethylamine, and the mixture was homogeneously dissolved. Next, 13.75 g (175.2 mmol) of acetyl chloride was added to the resultant mixture with cooling with ice. The reaction was conducted at a room temperature for 24 hours. The reaction mixture was poured into 500 ml of an iced water and a solid was formed by stirring. The resultant solid was collected by filtration, dried, and recrystallized from a mixed solvent of hexane/toluene to give 40.3 g (166.5 mmol) of benzyl-(4-acetoxyphenyl)ether.
Reaction SMILES: CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[NH2:17][CH2:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:36])[F:35])[CH2:23][CH2:22]1)=[O:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[C:61]1([C:67]2[O:71][C:70]([C:72](O)=[O:73])=[CH:69][CH:68]=2)[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>CN(C=O)C.O>[O:20]=[C:19]([N:21]1[CH2:22][CH2:23][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:35])[F:36])[CH2:25][CH2:26]1)[CH2:18][NH:17][C:72]([C:70]1[O:71][C:67]([C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)=[CH:68][CH:69]=1)=[O:73]
Reactant: O=C(O)c1ccc(-c2ccccc2)o1
Reactant: NCC(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1)c1ccc(-c2ccccc2)o1
Temperature: 25 °C
Reaction time: 8 h
Yield: 44.1 %

Procedure:
DIPEA (82 mg, 0.109 mL, 0.64 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt, (109 mg, 0.26 mmol) in DMF (1 mL). HOBT (34 mg, 0.26 mmol) and EDCI.HCl (49 mg, 0.26 mmol) were added at room temperature. After 2 minutes 5-phenyl furoic acid (40 mg, 0.21 mmol) was added. The resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford 45 mg (40% yield) of 5-phenyl-furan-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity %: 84.97, HPLC Purity: 92.51%, 1H NMR (DMSO-d6): δ 8.6 (t, 1H), 8.0-7.9 (d, 2H) 7.9-7.6 (m, 3H), 7.6-7.5 (bt, 1H), 7.5 (t, 2H), 7.4-7.3 (m, 1H), 7.2 (m, 1H), 7.1 (d, 1H), 4.2-4.1 (m, 2H), 3.8-3.5 (m, 4H), 3.4 (m, 2H), 3.2-3.1 (m, 2H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:2]1.[CH3:16][N:17]([CH3:31])[C:18]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.C(O)(=O)C>ClCCCl>[NH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([CH:3]2[CH2:4][CH2:5][CH2:6][N:1]([CH:21]3[CH2:20][CH2:19][C:18]([N:17]([CH3:31])[CH3:16])([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:23][CH2:22]3)[CH2:2]2)=[CH:8]1
Reactant: CN(C)C1(c2ccccc2)CCC(=O)CC1
Reactant: c1ccc2c(C3CCCNC3)c[nH]c2c1
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CN(C)C1(c2ccccc2)CCC(N2CCCC(c3c[nH]c4ccccc34)C2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
3-piperidine-3-yl-1H-indole (233 mg, 1.16 mmole) and 4-dimethylamino-4-phenylcyclohexanone (253 mg, 1.16 mmole) were dissolved in dry 1,2-dichloroethane (20 ml). Glacial acetic acid (1.16 mmole) and sodium triacetoxy boron hydride (350 mg, 1.63 mmole) were added to this mixture. The mixture was then stirred for 24 hours at RT. The reaction mixture was worked up by distilling off the 1,2-dichloroethane and diluting with water (20 ml). The reaction mixture was adjusted to pH 11 with 5M NaOH and extracted with EE (3×20 ml). The organic phase was dried with Na2SO4 and concentrated by evaporation. The product was a mixture of two diastereoisomeric compounds, which were separated by chromatography with methanol. The non-polar diastereoisomer was obtained as a colourless oil in a yield of 208 mg (45%) and the polar diastereoisomer was obtained as a colourless oil in a yield of 50 mg (11%).
Reaction SMILES: Br[C:2]1[N:19]([CH2:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]2)[C:5]2[C:6]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1.[NH:28]1[CH2:35][CH2:34][CH2:33][C@H:29]1[C:30]([OH:32])=[O:31]>>[Cl:18][C:16]1[CH:17]=[C:12]([C:6]2[C:5]3[N:19]([CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]4)[C:2]([N:28]4[CH2:35][CH2:34][CH2:33][C@H:29]4[C:30]([OH:32])=[O:31])=[N:3][C:4]=3[CH:9]=[C:8]([C:10]#[N:11])[N:7]=2)[CH:13]=[N:14][CH:15]=1
Reactant: O=C(O)[C@@H]1CCCN1
Reactant: C[C@H]1CC[C@H](Cn2c(Br)nc3cc(C#N)nc(-c4cncc(Cl)c4)c32)CC1
Product: C[C@H]1CC[C@H](Cn2c(N3CCC[C@H]3C(=O)O)nc3cc(C#N)nc(-c4cncc(Cl)c4)c32)CC1

Procedure:
(S)-1-(4-(5-chloropyridin-3-yl)-6-cyano-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-2-yl)pyrrolidine-2-carboxylic acid was prepared using a procedure analogous to that described in Example 3.94 (Step 1) using 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1) and L-proline. MS ESI calc'd. for C25H27ClN6O2 [M+H]+ 479. found 479.
Reaction SMILES: [C:1]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:27])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24]O)[CH3:19])[CH2:12][CH2:11]1.[NH2:34][C:35]1[CH:47]=[CH:46][C:38]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[CH:37][CH:36]=1>>[C:42]([O:41][C:39](=[O:40])[C:38]1[CH:46]=[CH:47][C:35]([NH:34][CH2:24][CH2:23][CH2:22][CH2:21][C:20]([N:18]([CH2:17][CH2:16][N:13]2[CH2:12][CH2:11][CH:10]([O:9][C:8](=[O:27])[NH:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:15][CH2:14]2)[CH3:19])=[O:26])=[CH:36][CH:37]=1)([CH3:43])([CH3:44])[CH3:45]
Reactant: CC(C)(C)OC(=O)c1ccc(N)cc1
Reactant: CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)CCCCO
Product: CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)CCCCNc1ccc(C(=O)OC(C)(C)C)cc1
Yield: 77.3 %

Procedure:
The compound (242 mg, 0.534 mmol) obtained in Example 31a was used to give a crude aldehyde compound (252 mg) according to the method described in Example 4g. The resulting crude aldehyde compound and tert-butyl 4-aminobenzoate (92 mg, 0.475 mmol) were used to give the title compound (231 mg; yield, 69%) as a white solid according to the method described in Example 18b.
Reaction SMILES: Cl.[NH:2]1[CH2:5][CH:4]([C:6]2[C:11]([Cl:12])=[N:10][CH:9]=[CH:8][N:7]=2)[CH2:3]1.Cl[C:14]1[N:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[Cl:12][C:11]1[C:6]([CH:4]2[CH2:5][N:2]([C:14]3[N:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]=3)[CH2:3]2)=[N:7][CH:8]=[CH:9][N:10]=1
Reactant: Clc1nccnc1C1CNC1
Reactant: Clc1ncc2ccccc2n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Clc1nccnc1C1CN(c2ncc3ccccc3n2)C1
Temperature: 110 °C
Reaction time: 17 h
Yield: 47.1 %

Procedure:
2-(Azetidin-3-yl)-3-chloropyrazine hydrochloride (1.50 g, 7.28 mmol), 2-chloroquinazoline (1.20 g, 7.28 mmol, Parkway Scientific), and cesium carbonate (5.22 g, 16.0 mmol, Fluka) were mixed in DMF (30 mL) in a round bottom flask under a nitrogen atmosphere. The mixture was stirred at 110° C. for 17 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude mixture was purified via silica gel flash column chromatography eluting with 0% to 100% EtOAc in hexanes to give 1.02 g (47%) of a yellow amorphous solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.41-4.50 (m, 1H) 4.58-4.63 (m, 2H) 4.65-4.72 (m, 2H) 7.22-7.28 (m, 1H) 7.61-7.72 (m, 3H) 8.28 (d, J=2.35 Hz, 1H) 8.51 (d, J=2.35 Hz, 1H) 9.04 (s, 1H). m/z=298 (M+1).
Reaction SMILES: [C:1]1(=[O:8])[O:7][CH2:6][CH2:5][CH2:4]CC1.[CH3:9][C@@H:10]1[O:17][C:15](=[O:16])[C@H:14]([CH3:18])[O:13][C:11]1=[O:12]>>[CH3:9][C@@H:10]1[O:17][C:15](=[O:16])[C@H:14]([CH3:18])[O:13][C:11]1=[O:12].[C:1]1(=[O:8])[O:7][CH2:6][CH2:5][CH2:4][O:12]1
Reactant: O=C1CCCCCO1
Agent: C[C@@H]1OC(=O)[C@H](C)OC1=O
Product: O=C1OCCCO1

Procedure:
The copolymer is prepared as in Example 15, except substituting trimethylene carbonate for ε-caprolactone, while maintaining an identical l-lactide mole fraction in the initial charge. The anticipated inherent viscosity is about 1.51 dl/g.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH:7]([CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)[CH2:6]2.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28]([OH:31])(=[O:30])=[O:29])=[CH:24][CH:23]=1>O=[Pt]=O.CO>[C:22]1([CH3:32])[CH:23]=[CH:24][C:25]([S:28]([OH:31])(=[O:29])=[O:30])=[CH:26][CH:27]=1.[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH:7]([CH2:15][CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)[CH2:6]2
Reactant: COc1cc2c(cc1OC)C(=O)C(Cc1ccncc1)C2
Agent: O=[Pt]=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Product: COc1cc2c(cc1OC)C(=O)C(CC1CCNCC1)C2
Temperature: 25 °C
Yield: 108.8 %

Procedure:
0.60 g of 2,3-dihydro-5,6-dimethoxy-2-((pyridin-4-yl)methyl)inden-1-one, and 0.36 g p-toluenesulfonic acid salt were added to 30 mL of anhydrous methanol. 60 milligrams of PtO2 were added. The reaction mixture was stirred at room temperature, with H2 being added at 1 atmosphere for 6 hours. Solids were filtered off. The filtrate was concentrated and dried in vacuo to afford 1.05 g of foam with 100% yield. Liquid chromatography analysis of this product showed 97% purity.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]1=[O:11].[N+:12]([O-])([OH:14])=[O:13]>S(=O)(=O)(O)O>[N+:12]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[NH:1][C:2](=[O:11])[CH2:3][CH2:4]2)([O-:14])=[O:13]
Reactant: O=C1CCc2ccccc2N1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: O=C1CCc2cc([N+](=O)[O-])ccc2N1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 3,4-dihydroquinolin-2-(1H)-one (1.50 g) in 78% sulfuric acid (300 mL) at RT, a mixture of 69% nitric acid (0.84 mL) in 78% sulfuric acid (60 mL) was added. The reacting mixture was stirred at RT for 15 min, poured into ice-water, and extracted with methylene chloride (3×200 mL). The organic extracts were combined, washed with brine (4×), dried over anhydrous magnesium sulfate, filtered and concentrated onto silica gel. The residue was loaded onto a column of silica gel, and eluted with 3% methanol in chloroform. Collection and concentration of appropriate fractions provided the nitroquinolinone 11-2.
Reaction SMILES: [CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[NH:12][CH:11]([CH3:19])[CH2:10][C:9]1=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]1(=[O:35])[N:25]([CH2:26][C:27](Cl)=[O:28])[C:24](=[O:30])[C:23]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:22]12>C(OCC)C>[CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([C:27](=[O:28])[CH2:26][N:25]2[C:24](=[O:30])[C:23]3=[CH:31][CH:32]=[CH:33][CH:34]=[C:22]3[C:21]2=[O:35])[CH:11]([CH3:19])[CH2:10][C:9]1=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cl)CN1C(=O)c2ccccc2C1=O
Reactant: CC1CC(=O)N(Cc2ccccc2)c2ccccc2N1
Solvent: CCOCC
Product: CC1CC(=O)N(Cc2ccccc2)c2ccccc2N1C(=O)CN1C(=O)c2ccccc2C1=O
Yield: 61 %

Procedure:
The titled compound was synthesized from 1-benzyl-4-methyl-1,3,4,5-tetrahydro-1,5-benzodiazepin-2(2H)-one and phthalimidoacetyl chloride in substantially the same manner as in Working Example 46. Yield 61%. m.p. 248°-250° C. (diethyl ether).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[N+:11]([C:14]1[CH:19]=[CH:18][C:17](O)=[CH:16][CH:15]=1)([O-:13])=[O:12]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([O:10][C:17]2[CH:18]=[CH:19][C:14]([N+:11]([O-:13])=[O:12])=[CH:15][CH:16]=2)[CH3:9])[CH:3]=1
Reactant: CC(O)c1cccc(F)c1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Product: CC(Oc1ccc([N+](=O)[O-])cc1)c1cccc(F)c1
Yield: 77 %

Procedure:
Prepared in analogy to example 16a) from 1-(3-fluoro-phenyl)-ethanol (Balasubramanian et al., Synth. Commun., 1994, 24 (8), 1049) and 4-nitrophenol. Yellow oil. Yield=77%. MS: m/e=261.2 (M+).
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[N:11]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3([C:24]#N)[CH2:23][CH2:22]3)=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.C([OH:29])(C)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N:11]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3([CH:24]=[O:29])[CH2:23][CH2:22]3)=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: N#CC1(c2ccc3ncccc3c2)CC1
Reactant: CC(C)O
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: O=CC1(c2ccc3ncccc3c2)CC1
Temperature: -2.5 °C
Reaction time: 3 h

Procedure:
Diisobutylaluminum hydride (1M in THF, 96 mL, 96 mmol) was added to a solution of 1-quinolin-6-ylcyclopropanecarbonitrile (12.4 g, 63.9 mmol) in toluene (120 mL) at −78° C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to −5 to 0° C., and stirred at that temperature for 3 h. The reaction mixture was cooled to −60° C. Isopropyl alcohol (10 mL) was carefully added dropwise. After stirring for 30 min, the reaction mixture was warmed to −5 to 0° C. The reaction mixture was diluted with ethyl acetate, quenched with water and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered through a pad of silica gel eluting with 40% ethyl acetate in hexanes. The filtrate was concentrated to yield the desired product. (12 g, 95.1%).