Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:10][C:9]([C:11]([OH:13])=O)=[CH:8][C:7]=1[CH3:14])=[O:5])[CH3:2].CC[N:17](C(C)C)[CH:18]([CH3:20])[CH3:19].C(N)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:14][C:7]1[CH:8]=[C:9]([C:11]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:13])[NH:10][C:6]=1[C:4]([O:3][CH2:1][CH3:2])=[O:5]
Reactant: CCOC(=O)c1[nH]c(C(=O)O)cc1C
Reactant: CCN(C(C)C)C(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CC(C)N
Product: CCOC(=O)c1[nH]c(C(=O)NC(C)C)cc1C
Yield: 5.3 %

Procedure:
To a solution of 5-[(ethyloxy)carbonyl]-4-methyl-1H-pyrrole-2-carboxylic acid (0.160 g, 0.812 mmol) in DMF (4 ml) was added DIPEA (0.140 mL, 0.790 mmol). The reaction mixture was stirred and the solution was divided into four equal portions, one of which was added to a glass vial with a stir bar. To the vial was added isopropylamine (0.017 mL, 0.2 mmol) and HATU (0.075 g, 0.197 mmol) and the reaction mixture stirred overnight. Purification was accomplished by RPHPLC (water:acetonitrile with 0.1% TFA). The desired fractions were collected and lypholized to afford ethyl 3-methyl-5-{[(1-methylethyl)amino]carbonyl}-1H-pyrrole-2-carboxylate (0.010 g, 47%) as an oil. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.58 (br. s., 1H) 8.07 (s, 1H) 6.60 (s, 1H) 4.26 (q, 2H) 3.97-4.12 (m, 1H) 2.24 (s, 3H) 1.30 (t, 3H) 1.14 (d, 6H). MS: m/z 239.4 (M+1).
Reaction SMILES: [F:1][CH:2]([F:29])[C@@:3]1([C:10]2[CH:15]=[C:14]([NH:16][C:17]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([N+:25]([O-])=O)=[CH:19][N:18]=3)[CH:13]=[CH:12][C:11]=2[F:28])[CH2:8][O:7][CH2:6][C:5]([NH2:9])=[N:4]1>CCO.[Pd]>[NH2:9][C:5]1[CH2:6][O:7][CH2:8][C@:3]([C:10]2[CH:15]=[C:14]([NH:16][C:17]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([NH2:25])=[CH:19][N:18]=3)[CH:13]=[CH:12][C:11]=2[F:28])([CH:2]([F:1])[F:29])[N:4]=1
Reactant: COc1cc([N+](=O)[O-])cnc1Nc1ccc(F)c([C@]2(C(F)F)COCC(N)=N2)c1
Agent: [Pd]
Solvent: CCO
Product: COc1cc(N)cnc1Nc1ccc(F)c([C@]2(C(F)F)COCC(N)=N2)c1
Reaction time: 1 h

Procedure:
To a solution of (R)-5-difluoromethyl-5-[2-fluoro-5-(3-methoxy-5-nitro-pyridin-2-ylamino)-phenyl]-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (80 mg, 0.179 mmol) in EtOH (10 ml) was added Pd—C (10%, 50 mg) the mixture was set under an atmosphere of hydrogen and stirred for 1 h. The catalyst was filtered off, the mixture diluted with DCM (20 ml) aq. sat. Na2CO3 (5 ml) was added and stirred for 5 min. The layers were separated, the aq. phase extracted with DCM (20 ml), the combined organic layers were washed with aq. sat. Na2CO3 (5 ml), dried with MgSO4 and the solvent removed under reduced pressure. The residue was purified by prep. TLC on silica gel (DCM/MeOH 9:1) to afford the title compound as purple semi-solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH3:7])=[CH:3][CH:2]=1.[CH2:8]([Br:30])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>>[CH2:8]([Br:30])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].[NH+:1]1[CH:6]=[CH:5][C:4]([CH3:7])=[CH:3][CH:2]=1
Reactant: Cc1ccncc1
Agent: CCCCCCCCCCCCCCCCCCCCCCBr
Product: Cc1cc[nH+]cc1

Procedure:
Referring to FIG. 1, γ-picoline (VI) has quaternised with docosyl bromide (n-C22H45Br) at 125° C. to produce γ-picolinium docosyl bromide (VII). This compound was then condensed with N,N-dimethyl-p-amino-benzaldehyde in refluxing methanol in the presence of piperidine for 16 hours. This reaction produced the intermediate alcohol IX presumably via an intermediate VIII. The intermediate alcohol IX eliminated water to give the stilbazolium dye X, which crystallised out on cooling the reaction mixture. Dye X was filtered off and purified by repeated recrystalisation from methanol (yield 47%).
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([OH:23])[N:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[C:24]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])(=[O:28])[C@@H:25]([CH3:27])O.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.C(Cl)Cl.CO>[C:30]([O:29][C:24](=[O:28])[C@@H:25]([O:23][C:21]1[N:20]=[CH:19][C:16]2[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]=2[CH:22]=1)[CH:10]=[C:9]([C:8]1[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][N:7]=1)[N:18]=3)[CH3:27])([CH3:33])([CH3:32])[CH3:31]
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1cnc(O)cc1OCC2
Reactant: C[C@@H](O)C(=O)OC(C)(C)C
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)n1ncnc1-c1cn2c(n1)-c1cnc(O[C@@H](C)C(=O)OC(C)(C)C)cc1OCC2

Procedure:
2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-ol from Example 93, (+)-tert-butyl d-lactate, diisopropylazodicarboxylate (DIAD), and triphenylphosphine were reacted in THF. The crude product was subjected to flash chromatography (SiO2, gradient 0-5% methanol in DCM) to give (S)-2-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-yloxy]-propionic acid tert-butyl ester as a yellow oil contaminated with triphenylphosphine oxide, no further purification was undertaken (206 mg, 49% based on NMR quantification of PPh3O). LCMS: RT=3.74 min, [M+H]+=441
Reaction SMILES: C(O)(C(F)(F)F)=O.[CH2:8]([C@@H:15]([CH2:38][CH2:39][C@H:40]([CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C:41]([NH:43][C@@H:44]1[C:50](=[O:51])[N:49]2[C@H:52]([C:56]([O:58]C(C)(C)C)=[O:57])[CH2:53][CH2:54][CH2:55][N:48]2[CH2:47][CH2:46][CH2:45]1)=[O:42])[C:16]([NH:18][C@@H:19]1[C:25](=[O:26])[N:24]2[C@H:27]([C:31]([O:33]C(C)(C)C)=[O:32])[CH2:28][CH2:29][CH2:30][N:23]2[CH2:22][CH2:21][CH2:20]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH2:8]([C@@H:15]([CH2:38][CH2:39][C@H:40]([CH2:63][C:64]1[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=1)[C:41]([NH:43][C@@H:44]1[C:50](=[O:51])[N:49]2[C@H:52]([C:56]([OH:58])=[O:57])[CH2:53][CH2:54][CH2:55][N:48]2[CH2:47][CH2:46][CH2:45]1)=[O:42])[C:16]([NH:18][C@@H:19]1[C:25](=[O:26])[N:24]2[C@H:27]([C:31]([OH:33])=[O:32])[CH2:28][CH2:29][CH2:30][N:23]2[CH2:22][CH2:21][CH2:20]1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCN2CCC[C@H](NC(=O)[C@H](CC[C@H](Cc3ccccc3)C(=O)N[C@H]3CCCN4CCC[C@@H](C(=O)OC(C)(C)C)N4C3=O)Cc3ccccc3)C(=O)N12
Solvent: O=C(O)C(F)(F)F
Product: O=C(N[C@H]1CCCN2CCC[C@@H](C(=O)O)N2C1=O)[C@H](CC[C@H](Cc1ccccc1)C(=O)N[C@H]1CCCN2CCC[C@@H](C(=O)O)N2C1=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 101 %

Procedure:
TFA (0.075 mL) was added to a solution of di-tert-butyl (1S,9S,1′S,9′S)-9,9′-(((2R,5R)-2,5-dibenzyl-1,6-dioxo-1,6-hexanediyl)diimino)bis(10-oxooctahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate) (28 mg, 0.033 in DCM, 0.25 mL). The reaction mixture was stirred overnight at rt. The reaction mixture was concentrated and placed under vacuum to give (1S,9S,1′S,9′S)-9,9′-(((2R,5R)-2,5-dibenzyl-1,6-dioxo-1,6-hexanediyl)diimino)bis(10-oxooctahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid) (25 mg, 0.033 mmol, 100% yield). Anal. Calcd. for C40H52N6O8 m/z 744.8. found: 745.6 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11]Br)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:13]([NH:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][N:25]2[CH2:26][CH2:27][CH:22]([NH:21][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:23][CH2:24]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=C(NC1CCNCC1)c1ccccc1
Reactant: O=[N+]([O-])c1ccc(CCBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Product: O=C(NC1CCN(CCc2ccc([N+](=O)[O-])cc2)CC1)c1ccccc1

Procedure:
p-Nitrophenylethyl bromide (1.15 g.) was refluxed for 20 hours in isopropyl alcohol (75 ml.) with 4-benzamidopiperidine (1.032 g.) and anhydrous potassium carbonate (1.037 g.). The mixture was filtered hot, refrigerated and product was filtered off (547 mg.), washed with cold isopropyl alcohol and ether. The filtrate was evaporated to yield more product (1.4 g.). Recrystallisation from a mixture of benzene and petroleum ether (b.p. 40°-60° C.) gave the title compound, m.p. 209°-216° C. (Found: C, 68.2; H, 6.7; N, 11.8. C20H23N3O3 requires C, 68.0; H, 6.6; N, 11.9%).
Reaction SMILES: [C:1]([C@H:4]([OH:34])[CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:24][CH2:23][CH:22]([N:25](C)[C:26](=O)OC(C)(C)C)[CH2:21][CH2:20]4)[C:8]=3[C:7]1=2)(=[O:3])[NH2:2].Cl>ClCCl>[OH:34][C@H:4]([CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:20][CH2:21][CH:22]([NH:25][CH3:26])[CH2:23][CH2:24]4)[C:8]=3[C:7]1=2)[C:1]([NH2:2])=[O:3]
Reactant: CN(C(=O)OC(C)(C)C)C1CCC(Oc2ncnc3sc4c(c23)[C@@H](C[C@@H](O)C(N)=O)CC4)CC1
Agent: Cl
Solvent: ClCCl
Product: CNC1CCC(Oc2ncnc3sc4c(c23)[C@@H](C[C@@H](O)C(N)=O)CC4)CC1
Temperature: 0 °C
Reaction time: 5 h
Yield: 88.3 %

Procedure:
Into a 10-mL round-bottom flask was placed a solution of tert-butyl N-(4-[[(3R)-3-[(2R)-2-carbamoyl-2-hydroxyethyl]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (0.7 g, 1.16 mmol, 1.00 equiv) in dichloromethane (10 mL) at 0° C. under nitrogen. Then hydrochloric acid (12 M, 2.0 mL) was added and the resulting solution was stirred for 5 h at 0° C. After completion of the reaction, the solvents were evaporated under reduced pressure. The residue was neutralized with 2 M aqueous sodium bicarbonate and extracted with 3×60 mL of dichloromethane. The organic layers were combined and washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 400 mg (crude) of (2R)-2-hydroxy-3-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide as a yellow oil. 1H NMR (300 MHz, CD3OD): δ 8.46 (s, 1H), 5.30 (m, 1H), 4.08 (m, 1H), 3.66 (m, 1H), 3.19-3.12 (m, 1H), 3.02-2.96 (m, 1H), 2.74-2.25 (m, 9H), 2.13-2.10 (m, 2H), 1.82-1.68 (m, 3H), 1.45-1.25 (m, 2H). MS: m/z 391 (M+H)+.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][CH2:15][C:16]2[CH:25]=[C:24]3[C:19]([CH2:20][CH2:21][O:22][C:23]3([CH3:30])[C:26]([F:29])([F:28])[F:27])=[CH:18][C:17]=2[O:31][CH3:32])[C@@H:9]1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=O)(C)(C)C.[ClH:39]>C(OCC)(=O)C>[ClH:39].[ClH:39].[CH3:32][O:31][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:16]=1[CH2:15][NH:14][C@H:10]1[CH2:11][CH2:12][CH2:13][NH:8][C@H:9]1[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:23]([CH3:30])([C:26]([F:29])([F:27])[F:28])[O:22][CH2:21][CH2:20]2
Reactant: COc1cc2c(cc1CN[C@H]1CCCN(C(=O)OC(C)(C)C)[C@H]1c1ccccc1)C(C)(C(F)(F)F)OCC2
Agent: Cl
Solvent: CCOC(C)=O
Product: COc1cc2c(cc1CN[C@H]1CCCN[C@H]1c1ccccc1)C(C)(C(F)(F)F)OCC2
Yield: 28.4 %

Procedure:
To a stirred solution of 1-tert-butoxycarbonyl-(2S,3S)-3-(6-methoxy-1-methyl-1-trifluoromethylisochroman-7-yl)methylamino-2-phenylpiperidine (325 mg, 0.61 mmol) in ethyl acetate (5 ml) was added a methanolic HCl solution dropwise under nitrogen at room temperature for 8 hours. The solvent was removed, and recrystallized from ethanol to give the title compound (88 mg, 28.4%). mp: 193-201° C. 1H-NMR (major isomer, free amine, CDCl3): 7.33-7.20 (m, 5H), 6.95 (s, 1H), 6.43 (s, 1 H), 4.13-4.09 (m, 1H), 3.92-3.84 (m, 2H), 3.62 (d, J=13.9 Hz, 1H), 3.51 (s, 3H), 3.33 (d, J=13.9 Hz, 1H), 3.31-3.24 (m, 1H), 2.84-2.74 (m, 4H), 2.12-2.07 (m, 1H), 1.94-1.82 (m, 1H), 1.67-1.62 (m, 1H), 1.59 (s, 3H), 1.43-1.38 (m, 1H)
Reaction SMILES: C(OC([NH:8][C:9]1([C@@H:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[CH2:11][CH2:10]1)=O)(C)(C)C.C(N(CC)CC)C.CS(C)=O.F[C:29]1[CH:38]=[C:37]2[C:32]([C:33](=[O:46])[C:34]([C:43]([OH:45])=[O:44])=[CH:35][N:36]2[C@@H:39]2[CH2:41][C@@H:40]2[F:42])=[CH:31][CH:30]=1>O>[NH2:8][C:9]1([C@@H:12]2[CH2:16][CH2:15][N:14]([C:29]3[CH:38]=[C:37]4[C:32]([C:33](=[O:46])[C:34]([C:43]([OH:45])=[O:44])=[CH:35][N:36]4[C@@H:39]4[CH2:41][C@@H:40]4[F:42])=[CH:31][CH:30]=3)[CH2:13]2)[CH2:10][CH2:11]1
Reactant: O=C(O)c1cn([C@@H]2C[C@@H]2F)c2cc(F)ccc2c1=O
Reactant: CC(C)(C)OC(=O)NC1([C@@H]2CCNC2)CC1
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: O
Product: NC1([C@@H]2CCN(c3ccc4c(=O)c(C(=O)O)cn([C@@H]5C[C@@H]5F)c4c3)C2)CC1
Reaction time: 0.5 h
Yield: 73.6 %

Procedure:
After adding 3-(R)-[1-[N-(tert-butoxycarbonyl)amino]cyclopropyl]pyrrolidine (203 mg, 817 μmol) and triethylamine (0.5 ml) to dried dimethyl sulfoxide (1 ml), 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (197 mg, 743 μmol) was added thereto and the mixture was heated reflux for 15 hours under a nitrogen atmosphere. After letting the reaction solution cool, water (30 ml) was added to the reaction solution while cooling with ice, and the precipitated crystals were filtered out and washed well with water. After adding concentrated hydrochloric acid (5 ml) to the obtained crystals while cooling with ice, stirring at the same temperature was performed for 30 minutes. 1 mol/l hydrochloric acid (10 ml) was then added to the reaction solution, and after washing the yellow acidic aqueous solution with chloroform (50 ml×2), the pH was adjusted to 12.0 with an aqueous sodium hydroxide solution. After adjusting the pH of the basic aqueous solution to 7.4 with 1 mol/l hydrochloric acid, extractions into chloroform (100 ml×3) and a 95:5 mixture of chloroform:methanol (100 ml×2) were performed. The organic layers were then combined, and after drying the organic layer over anhydrous sodium sulfate, the solvent was evapolated under a reduced pressure. The residue obtained was purified by recrystallization in ethanol and then dried under a reduced pressure. 203 mg (74%) of the title compound was thereby obtained in the form of yellow crystals.
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:27]([F:30])([F:29])[F:28])[CH:25]=3)[N:20]=[CH:19][CH:18]=2)[CH:9]=1)=[O:7]>O1CCCC1.O>[C:6]([C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:27]([F:30])([F:28])[F:29])[CH:25]=3)[N:20]=[CH:19][CH:18]=2)[CH:9]=1)([OH:7])=[O:5]
Reactant: COC(=O)c1cn(-c2ccnc3ccc(C(F)(F)F)cc23)c2ccccc12
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cn(-c2ccnc3ccc(C(F)(F)F)cc23)c2ccccc12

Procedure:
0.32 g (7.63 mmol) of lithium hydroxide monohydrate and 8 cm3 of water are added to 0.94 g (2.54 mmol) of 3-methoxycarbonyl-1-(6-(trifluoromethyl)quinol-4-yl)-1H-indole dissolved in 8 cm3 of tetrahydrofuran. After stirring at reflux for 15 hours, the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is taken up in 20 cm3 of water (pH=10). The resulting aqueous solution is washed with 30 cm3 of ethyl acetate, adjusted to pH 6 with N hydrochloric acid and extracted with 50 cm3 of ethyl acetate. The organic phase is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is triturated in 20 cm3 of isopropyl ether and filtered off, resulting in 0.73 g of 3-carboxy-1-(6-(trifluoromethyl)quinol-4-yl)-1H-indole in the form of a white powder. Mass spectrum: m/e 356 (M+•).
Reaction SMILES: C(O)(=[O:19])CCCCCCC/C=C\CCCCCCCC.C(O)(=O)CCCCCCC/C=C\CCCCCC.[Cl-].[Al+3].[Cl-].[Cl-].C1(O)C=CC=CC=1.[C:50]1([CH:56]([CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[C:57]([OH:59])=[O:58])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>C1C=CC=CC=1>[C:50]1([CH:56]([CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[C:57]([OH:59])=[O:58])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.[OH:19][C:56]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[C:57]([OH:59])=[O:58]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: CCCCCC/C=C\CCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCCC(C(=O)O)c1ccccc1
Agent: [Al+3]
Solvent: Oc1ccccc1
Solvent: c1ccccc1
Product: CCCCCCCCCCCCCCCCC(O)(C(=O)O)c1ccccc1

Procedure:
Phenylstearic acid and hydroxyphenylstearic acid were prepared from commercial grade oleic acid which contained a few percent of palmitoleic acid by a Friedel-Crafts reaction using aluminum chloride as the catalyst, and benzene and phenol; respectively, as the arylating agents. Thereafter, phenyloctadecylnitrile was prepared on a continuous nitrile unit over bauxite catalyst at 280°-300°C from 1127 grams phenylstearic acid. A crude yield of 833.5 grams of phenyloctadecylnitrile was obtained. The product was a mixture of isomers, predominately the C8 to C14 and the C17 isomers with lesser proportions of other isomers. Similarly, hydroxyphenyloctadecylnitrile was obtained in 62 percent crude yield from the crude acid.
Reaction SMILES: [Cl-].[Cl:2][CH2:3][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[NH2-].[Na+].[Cl:25][C:26]1[C:31]2[C:32](=[O:44])[N:33]3[CH2:43][CH2:42][C@H:34]3[C:35]3[N:36]([CH:37]=[N:38][C:39]=3[CH:40]=O)[C:30]=2[CH:29]=[CH:28][CH:27]=1.N>O1CCCC1>[Cl:25][C:26]1[C:31]2[C:32](=[O:44])[N:33]3[CH2:43][CH2:42][C@H:34]3[C:35]3[N:36]([CH:37]=[N:38][C:39]=3/[CH:40]=[CH:3]\[Cl:2])[C:30]=2[CH:29]=[CH:28][CH:27]=1
Reactant: O=Cc1ncn2c1[C@@H]1CCN1C(=O)c1c(Cl)cccc1-2
Reactant: ClC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: N
Agent: [Cl-]
Agent: [NH2-]
Solvent: C1CCOC1
Product: O=C1c2c(Cl)cccc2-n2cnc(/C=C\Cl)c2[C@@H]2CCN12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
17.5 g of an equimolar mixture of chloromethyltriphenylphosphonium chloride and sodium amide was stirred for 15 minutes in 100 ml of tetrahydrofuran, whereby the temperature rose to 33°. 11.1 g (38.58 mmol) of (S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxaldehyde was then added portionwise thereto, whereby the temperature rose to 45° with the evolution of ammonia. The mixture was stirred at room temperature for a further 1 hour, filtered and the filtrate was evaporated. After chromatography on silica gel while eluting with cyclohexane/ether/isopropanol (3:3:1) and subsequent recrystallization from ethyl acetate there was obtained (S)-8-chloro-1-[(Z)-2-chlorovinyl]-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of melting point 189°-191°.
Reaction SMILES: [NH2:1][C@H:2]([C:11]([O:13][CH3:14])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[NH:15]([C:23]([O:25][C:26]([C:29]1[CH:38]=[C:35]([O:36][CH3:37])[CH:34]=[C:31]([O:32][CH3:33])[CH:30]=1)([CH3:28])[CH3:27])=[O:24])[C@H:16]([C:20](O)=[O:21])[CH:17]([CH3:19])[CH3:18].C1C=C2C(N(O)N=NC2=CC=1)=O>CN(C=O)C>[NH:15]([C:23]([O:25][C:26]([C:29]1[CH:30]=[C:31]([O:32][CH3:33])[CH:34]=[C:35]([O:36][CH3:37])[CH:38]=1)([CH3:28])[CH3:27])=[O:24])[C@@H:16]([C:20]([NH:1][C@H:2]([C:11]([O:13][CH3:14])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=[O:21])[CH:17]([CH3:18])[CH3:19]
Reactant: COc1cc(OC)cc(C(C)(C)OC(=O)N[C@H](C(=O)O)C(C)C)c1
Reactant: COC(=O)[C@@H](N)Cc1ccc(O)cc1
Agent: O=c1c2ccccc2nnn1O
Solvent: CN(C)C=O
Product: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](NC(=O)OC(C)(C)c1cc(OC)cc(OC)c1)C(C)C

Procedure:
Solution Phase Couplings with Ddz-Xxx-Pfp and Ddz-Xxx-ODhbt. The efficiency of acylation of ODhbt esters, in terms of both coupling and racemization, was examined through the acylation of a simple amino acid alkyl ester, i.e., the acylation of H-Tyr-OMe with Ddz-L-Val-Dhbt and Ddz-D-Val-ODhbt in DMF at 0.1M. The dipeptides Ddz-L-Val-Tyr-OMe and Ddz-D-Val-Tyr-OMe were obtained in high yield (>90%) after a simple extractive workup and the Ddz-L-Val-Tyr-OMe gave a clean, single peak HPLC trace. Ddz-D-Val-ODhbt was not obtained as a solid, as it was contaminated with 5% of the azidobenzoate impurity, as mentioned by Atherton, et al.,54 which showed up in the HPLC trace. Both dipeptides gave clean 1H-NMR spectra. The attempted separation of the diastereomeric dipeptides by HPLC was unsuccessful over a wide range of isocratic gradients. In the 1H-NMR spectra, however, there is a slight difference in shift of the Val α-CH between the two dipeptides, hence there is no evidence in either spectra of any measurable amount of racemization.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:5]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH3:17].Cl[CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:6][C:5]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH3:17]
Reactant: COCCCCOc1cc(O)ccc1C(=O)OC
Reactant: ClCCN1CCOCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: COCCCCOc1cc(OCCN2CCOCC2)ccc1C(=O)OC
Yield: 102.4 %

Procedure:
A suspension of 4-hydroxy-2-(4-methoxybutoxy)-benzoic acid methyl ester (2.0 g), 2-chloroethylmorpholine (11.8 g) and caesium carbonate (12.8 g) in acetone (30 ml) is stirred under reflux for 2 hours. Filtration and purification by FC (80 g of silica gel, eluant F and ethyl acetate-conc. ammonia 10:0.1) yield 2-(4-methoxy butoxy)-4-(2-morpholin-4-ylethoxy)-benzoic acid methyl ester (2.96 g), Rf (N)=0.73, in the form of a pale-yellow oil.