Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:21]C)=[C:11]4[O:12][C@H:13]5[C@@H:14]([OH:20])[CH:15]=[CH:16][C@@H:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.Cl.N1C=CC=CC=1.[OH-].[Na+]>O>[CH:8]1[C:7]2[CH2:19][C@H:18]3[N:2]([CH2:3][CH2:4][C@@:5]45[C@H:17]3[CH:16]=[CH:15][C@H:14]([OH:20])[C@@H:13]4[O:12][C:11]([C:6]=25)=[C:10]([OH:21])[CH:9]=1)[CH3:1]
Reactant: COc1ccc2c3c1O[C@H]1[C@@H](O)C=C[C@H]4[C@@H](C2)N(C)CC[C@@]341
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccncc1
Solvent: O
Product: CN1CC[C@]23c4c5ccc(O)c4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5

Procedure:
Rapoport et al. (J.A.C.S. 5485 and 5900 73 1951) have claimed a 22% yield of morphine from codeine employing pyridine hydrochloride as the cleavage agent. 1.00g codeine was heated with pyridine hydrochloride for six minutes under nitrogen. The reaction mixture was dissolved in 20ccm water, basified with 10ccm 4N NaOH and extracted with chloroform to yield 0.210g morphine.
Reaction SMILES: CS(O[CH2:6][C:7]1[N:12]=[CH:11][C:10]2[N:13]=[CH:14][N:15]([C:16]3[S:17][C:18]([C:34](=[O:36])[NH2:35])=[C:19]([O:21][C@@H:22]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[C:30]([F:33])([F:32])[F:31])[CH3:23])[CH:20]=3)[C:9]=2[CH:8]=1)(=O)=O.[CH2:37]([N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1)[CH:38]([CH3:40])[CH3:39]>ClCCl>[CH2:37]([N:41]1[CH2:46][CH2:45][N:44]([CH2:6][C:7]2[N:12]=[CH:11][C:10]3[N:13]=[CH:14][N:15]([C:16]4[S:17][C:18]([C:34]([NH2:35])=[O:36])=[C:19]([O:21][C@@H:22]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[C:30]([F:33])([F:31])[F:32])[CH3:23])[CH:20]=4)[C:9]=3[CH:8]=2)[CH2:43][CH2:42]1)[CH:38]([CH3:40])[CH3:39]
Reactant: CC(C)CN1CCNCC1
Reactant: C[C@@H](Oc1cc(-n2cnc3cnc(COS(C)(=O)=O)cc32)sc1C(N)=O)c1ccccc1C(F)(F)F
Solvent: ClCCl
Product: CC(C)CN1CCN(Cc2cc3c(cn2)ncn3-c2cc(O[C@H](C)c3ccccc3C(F)(F)F)c(C(N)=O)s2)CC1

Procedure:
In a similar manner as described for example 58, 108 mg of [1-(5-carbamoyl-4-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}-2-thienyl)-1H-imidazo[4,5-c]pyridin-6-yl]methyl methanesulfonate and 142.2 mg of 1-isobutylpiperazine in 2.5 ml dichloromethane give the title compound.
Reaction SMILES: C([O:3][C:4](=[O:40])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][CH:21]([C:24]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[OH:25])[CH2:20][CH2:19]2)=[CH:10][CH:9]=1)=[O:6])C.C(=O)(O)[O-].[Na+].O.C(O)(=O)C>C(O)C>[F:39][C:36]1[CH:37]=[CH:38][C:33]([C:24]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)([OH:25])[CH:21]2[CH2:22][CH2:23][N:18]([CH2:17][CH2:16][CH2:15][O:14][C:11]3[CH:12]=[CH:13][C:8]([NH:7][C:5](=[O:6])[C:4]([OH:40])=[O:3])=[CH:9][CH:10]=3)[CH2:19][CH2:20]2)=[CH:34][CH:35]=1
Reactant: CCOC(=O)C(=O)Nc1ccc(OCCCN2CCC(C(O)(c3ccc(F)cc3)c3ccc(F)cc3)CC2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Solvent: O
Product: O=C(O)C(=O)Nc1ccc(OCCCN2CCC(C(O)(c3ccc(F)cc3)c3ccc(F)cc3)CC2)cc1

Procedure:
A solution of [[4-[3-[4-[Bis(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]propoxy]phenyl]amino]oxoacetic acid ethyl ester in 50 ml of ethanol is treated with 20 ml of a 2N sodium bicarbonate solution and the mixture is heated at reflux overnight. The mixture is cooled and poured into 500 ml of water containing 10 ml of acetic acid. The resulting solution is collected by filtration and dried to give the title compound.
Reaction SMILES: C[O:2][C:3](=[O:16])[CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([SH:14])=[CH:8][C:7]=1[CH3:15].Cl[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)=[CH:21][C:20]=1[CH3:35]>>[CH3:13][O:12][C:10]1[C:9]([S:14][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:32])([F:33])[F:34])=[CH:27][CH:26]=3)=[CH:21][C:20]=2[CH3:35])=[CH:8][C:7]([CH3:15])=[C:6]([CH:11]=1)[O:5][CH2:4][C:3]([OH:2])=[O:16]
Reactant: COC(=O)COc1cc(OC)c(S)cc1C
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)ccc1CCl
Product: COc1cc(OCC(=O)O)c(C)cc1SCc1ccc(-c2ccc(C(F)(F)F)cc2)cc1C

Procedure:
The title compound was prepared in the manner analogous to Example 1F using 1D and 39B. MS m/z 491 (M+1).
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:23])[CH:4](CO)[NH:5][C:6](=[O:20])[C:7]1[C:12]([I:13])=[C:11]([NH2:14])[C:10]([I:15])=[C:9]([C:16]([OH:18])=[O:17])[C:8]=1[I:19].[C:24](Cl)(=[O:26])[CH3:25].[CH3:28]C(N(C)C)=O>>[CH3:1][NH:2][C:3](=[O:23])[CH2:4][N:5]([C:6](=[O:20])[C:7]1[C:12]([I:13])=[C:11]([NH:14][C:24](=[O:26])[CH3:25])[C:10]([I:15])=[C:9]([C:16]([OH:18])=[O:17])[C:8]=1[I:19])[CH3:28]
Reactant: CNC(=O)C(CO)NC(=O)c1c(I)c(N)c(I)c(C(=O)O)c1I
Reactant: CC(=O)Cl
Reactant: CC(=O)N(C)C
Product: CNC(=O)CN(C)C(=O)c1c(I)c(NC(C)=O)c(I)c(C(=O)O)c1I

Procedure:
Analogously to Example 3, 71.5 g. (74.5%) of N-3-carboxy-5-acetamido-2,4,6-triiodobenzoyl)-sarcosine methylamide, m.p. 270°-271° C. (under decomposition) is obtained from 90 g. (0.14 mole) of N-(3-carboxy-5-amino-2,4,6-triiodobenzoyl)-sarcosine methylamide (IV e), m.p. 238°-240° C. (decomposition) in 170 ml. of dimethylacetamide and 27.4 ml. of acetyl chloride.
Reaction SMILES: C([NH:4][C:5]1[CH:6]=[C:7]([CH:32]=[CH:33][CH:34]=1)[C:8]([NH:10][CH:11]([C:13]1[N:18]=[N:17][C:16]([NH:19][C:20]2[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=2)=[N:15][CH:14]=1)[CH3:12])=O)(=O)C.P(Cl)(Cl)(Cl)=O.Cl.[OH-].[Na+]>ClCCCl.CO>[NH2:4][C:5]1[CH:6]=[C:7]([C:8]2[N:18]3[C:13]([CH:14]=[N:15][C:16]([NH:19][C:20]4[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=4)=[N:17]3)=[C:11]([CH3:12])[N:10]=2)[CH:32]=[CH:33][CH:34]=1
Reactant: COc1cc(Nc2ncc(C(C)NC(=O)c3cccc(NC(C)=O)c3)nn2)cc(OC)c1OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CO
Solvent: ClCCCl
Product: COc1cc(Nc2ncc3c(C)nc(-c4cccc(N)c4)n3n2)cc(OC)c1OC
Temperature: 25 °C
Yield: 2.1 %

Procedure:
To a solution of 3-(acetylamino)-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 32) (110 mg, 0.24 mmol) in 1,2-dichloroethane (10 mL) was added phosphorous oxychloride (0.175 mL, 1.9 mmol). The mixture was refluxed for 6 hours, cooled to room temperature and more phosphorous oxychloride (0.10 mL, 1.0 mmol) was added. The reaction was then refluxed for 4 hours. After cooling to room temperature the reaction was diluted with methanol, then poured onto a mixture of ice and concentrated HCl. This mixture was brought to a pH of 8 by addition of concentrated aqueous NaOH. The mixture was then extracted with ethyl acetate, concentrated under vacuum and purified by reverse-phase HPLC to give 7-(3-aminophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (2 mg) as a yellow solid. 1H NMR (CD3OD): δ9.00 (s, 1H), 7.60 (d, J=7.87 Hz, 1H), 7.54 (s, 1H), 7.21 (t, J=7.78 Hz, 1H), 7.09 (s, 2H), 6.79 (dd, J=7.87 and 2.01 Hz, 1H), 3.77 (s, 6H), 3.73 (s, 3H), 2.56 (s, 3H). MS m/z 406 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:23]3[CH2:28]C[CH2:26][CH2:25][CH2:24]3)[CH2:14]OCC3CCCCC3)[C:11]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[OH:35][C:36]1[CH:45]=[CH:44][C:39]([C:40]([O:42][CH3:43])=[O:41])=[CH:38][N:37]=1.[C:46]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:47]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>>[CH3:43][O:42][C:40](=[O:41])[C:39]1[CH:44]=[CH:45][C:36]([O:35][CH2:14][CH:13]([N:12]2[C:11]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:10]=3[N:9]=[C:8]2[C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH:23]2[CH2:24][CH2:25][CH2:26][CH2:47][CH2:46][CH2:28]2)=[N:37][CH:38]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Fc1cc2nc(-c3ccc(Cl)cc3)n(C(COCC3CCCCC3)C3CCCCC3)c2cc1F
Reactant: COC(=O)c1ccc(O)nc1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Product: COC(=O)c1ccc(OCC(C2CCCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)nc1
Yield: 78 %

Procedure:
The title compound was prepared in analogy to Example 4, intermediate, from 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Example 1, intermediate c), methyl 6-hydroxynicotinate (commercially available), triphenylphosphine and di-tert-butyl azodicarboxylate. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30) to give the desired compound as a colorless solid (78%). MS (Turbo Spray): m/z=540.3 [M+H].
Reaction SMILES: C([N:3]([C:31](=O)[C:32]1[CH:37]=[CH:36][C:35](O)=[CH:34]C=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[C@@H:14]1[CH2:23][CH2:22][C:21]2[CH:20]=[C:19]([O:24]C(=O)C(C)(C)C)[CH:18]=[CH:17][C:16]=2[CH2:15]1)C.[N:40]1([C:47](=O)[CH2:48]Cl)[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>>[N:40]1([CH2:47][CH2:48][O:10][C:8]2[CH:7]=[CH:6][C:36]([CH2:37][CH2:32][CH2:31][NH:3][C:4]3[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=3[C@@H:14]3[CH2:23][CH2:22][C:21]4[CH:20]=[C:19]([OH:24])[CH:18]=[CH:17][C:16]=4[CH2:15]3)=[CH:35][CH:34]=2)[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1
Reactant: CCN(C(=O)c1ccc(O)cc1)c1cc(OC)c(OC)cc1[C@@H]1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Reactant: O=C(CCl)N1CCCCCC1
Product: COc1cc(NCCCc2ccc(OCCN3CCCCCC3)cc2)c([C@@H]2CCc3cc(O)ccc3C2)cc1OC
Yield: 89.2 %

Procedure:
Synthesized from pivalic acid (R)-6-{2-[ethyl(4-hydroxybenzoyl)amino]-4,5-dimethoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (16 mg) and 1-azepan-1-yl-2-chloroethanone (9.5 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (7.5 mg) was obtained.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][C:11]1[N:15]=[CH:14][N:13]([C:16]2[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=2)[N:12]=1>C(OC(O)C)C.O.CCOC(C)=O>[CH3:9][O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:20][C:19]2[CH:18]=[CH:17][C:16]([N:13]3[CH:14]=[N:15][C:11]([CH3:10])=[N:12]3)=[CH:22][CH:21]=2)[N:7]=1
Reactant: Cc1ncn(-c2ccc(N)cc2)n1
Reactant: COc1ccnc(Cl)n1
Agent: CCOC(C)O
Solvent: O
Solvent: CCOC(C)=O
Product: COc1ccnc(Nc2ccc(-n3cnc(C)n3)cc2)n1
Temperature: 75 °C

Procedure:
To a solution 2-chloro-4-methoxypyrimidine (2 g, 13.8 mmol) in ethoxyethanol (50 mL) was added 4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (1.7 g, 10.6 mmol). The reaction was warmed to 75° C. for 16 h, cooled, and diluted with water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc (4×). The combined organics were dried (MgSO4), and concentrated to give a near colorless solid which was homogeneous by analytical HPLC analysis and was used without further purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C.[CH3:35][C:36]1([CH3:55])[CH2:45][CH2:44][C:43]([CH3:47])([CH3:46])[C:42]2[CH:41]=[C:40]([C:48]3[N:53]=[C:52]([NH2:54])[CH:51]=[CH:50][CH:49]=3)[CH:39]=[CH:38][C:37]1=2.[OH-].[Na+]>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14](=[O:16])[NH:54][C:52]2[CH:51]=[CH:50][CH:49]=[C:48]([C:40]3[CH:39]=[CH:38][C:37]4[C:36]([CH3:55])([CH3:35])[CH2:45][CH2:44][C:43]([CH3:47])([CH3:46])[C:42]=4[CH:41]=3)[N:53]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCOC(C(=O)O)C1
Reactant: CC1(C)CCC(C)(C)c2cc(-c3cccc(N)n3)ccc21
Agent: CCOC(=O)N1c2ccccc2C=CC1OCC
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCOC(C(=O)Nc2cccc(-c3ccc4c(c3)C(C)(C)CCC4(C)C)n2)C1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
82 mg (0.36 mmol) of morpholine-2,4-dicarboxylic acid 4-tert-butyl ester and 97 mg (0.39 mmol) of ethyl 2-ethoxy-1,2-dihydroquinoline-1-carboxylate (EEDQ) are suspended in 2 ml of THF and stirred at room temperature for 20 min. 100 mg (0.36 mmol) of 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)pyridin-2-ylamine from step a are added to the mixture. The mixture is stirred further overnight, water is added, the mixture is adjusted to pH 9-10 using a 2N NaOH solution and extracted twice with EA. The combined organic phases are dried, filtered and evaporated (191 mg). The residue is purified by means of flash chromatography on silica gel.
Reaction SMILES: C(OC(=O)C1C=CC(N[C:12](=[O:38])[CH:13]([N:20]2[C:24]3[CH:25]=[C:26]([F:30])[C:27]([F:29])=[CH:28][C:23]=3[N:22]=[C:21]2[C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=2)[CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=CC=1)C.Cl[C:41]1C=CC(C2N(C(C3CCCCC3)C(NC[C@H]3CC[C@H](C(O)=O)CC3)=O)C3C=CC(F)=CC=3N=2)=C[CH:42]=1.[NH2:77][C:78]1[CH:83]=[CH:82][C:81]([CH:84]([CH3:88])[C:85]([OH:87])=[O:86])=[CH:80][C:79]=1[F:89]>CN(C)C1C=CN=CC=1>[CH2:41]([O:86][C:85](=[O:87])[CH:84]([C:81]1[CH:82]=[CH:83][C:78]([NH:77][C:12](=[O:38])[CH:13]([N:20]2[C:24]3[CH:25]=[C:26]([F:30])[C:27]([F:29])=[CH:28][C:23]=3[N:22]=[C:21]2[C:31]2[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=2)[CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:79]([F:89])[CH:80]=1)[CH3:88])[CH3:42]
Reactant: CC(C(=O)O)c1ccc(N)c(F)c1
Reactant: O=C(NC[C@H]1CC[C@H](C(=O)O)CC1)C(C1CCCCC1)n1c(-c2ccc(Cl)cc2)nc2cc(F)ccc21
Reactant: CCOC(=O)c1ccc(NC(=O)C(C2CCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)cc1
Agent: CN(C)c1ccncc1
Product: CCOC(=O)C(C)c1ccc(NC(=O)C(C2CCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)c(F)c1

Procedure:
The title compound was synthesized in analogy to example 22, intermediate d, from [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid (example 20, intermediate c), 2-(4-amino-3-fluoro-phenyl)-propionic acid and using 4-(dimethylamino)pyridine as a base.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:17]=[C:18]([C:20]([O:22]CC)=[O:21])[N:19]=2)[C:7]=1[CH2:8][P:9]([O:14]CC)([O:11]CC)=[O:10].[P:25]([CH2:29][C:30]1[C:31]2[N:32]([CH:36]=[C:37]([C:39]([OH:41])=[O:40])[N:38]=2)[CH:33]=[CH:34][CH:35]=1)([OH:28])([OH:27])=[O:26]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:17]=[C:18]([C:20]([OH:22])=[O:21])[N:19]=2)[C:7]=1[CH2:8][P:9]([OH:11])([OH:14])=[O:10].[P:25]([CH2:29][C:30]1[C:31]2[N:32]([CH:36]=[C:37]([C:39]([OH:41])=[O:40])[N:38]=2)[CH:33]=[CH:34][CH:35]=1)([OH:27])([OH:28])=[O:26]
Reactant: CCOC(=O)c1cn2c(CP(=O)(OCC)OCC)c(Cl)ccc2n1
Agent: O=C(O)c1cn2cccc(CP(=O)(O)O)c2n1
Product: O=C(O)c1cn2c(CP(=O)(O)O)c(Cl)ccc2n1

Procedure:
Following the procedure in Example 7, the product from Example 29 was refluxed in 4N. HCl (7 mL) for 7 h. Workup produced the title product HCl salt.
Reaction SMILES: Cl[C:2]1[C:7]([CH2:8][O:9][CH2:10][O:11][CH3:12])=[CH:6][C:5]([F:13])=[CH:4][N:3]=1.[C:14](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1>O1CCOCC1.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>[F:13][C:5]1[CH:6]=[C:7]([CH2:8][O:9][CH2:10][O:11][CH3:12])[C:2]([CH3:14])=[N:3][CH:4]=1
Reactant: COCOCc1cc(F)cnc1Cl
Reactant: O=C([O-])[O-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CB1OB(C)OB(C)O1
Agent: [K+]
Solvent: C1COCCO1
Product: COCOCc1cc(F)cnc1C
Reaction time: 2 h
Yield: 71.1 %

Procedure:
To a solution of 0.10 g of 2-chloro-5-fluoro-3-((methoxymethoxy)methyl)pyridine in 3 mL of dioxane, 0.20 g of potassium carbonate, 68 μL of trimethylboroxin and 56 mg of tetrakis(triphenylphosphine)palladium(0) were added, and the mixture was heated under reflux while stirring for 2 hours under a nitrogen atmosphere. Thereto were added 0.20 g of potassium carbonate, 68 μL of trimethylboroxin and 56 mg of tetrakis(triphenylphosphine)palladium(0), and the mixture was heated under reflux while stirring for 2 hours under a nitrogen atmosphere. Thereto were added 0.20 g of potassium carbonate, 68 μL of trimethylboroxin and 56 mg of tetrakis(triphenylphosphine)palladium(0), and the mixture was heated under reflux while stirring for 1 hour under a nitrogen atmosphere. The insoluble substance was filtered off, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of chloroform:methanol=100:1 to obtain 93 mg of a colorless oily substance. The substance was purified by basic silica gel column chromatography using an eluent of chloroform to obtain 64 mg of 5-fluoro-3-((methoxymethoxy)methyl)-2-methylpyridine as a colorless oily substance.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=2)=[CH:5][CH:4]=1.[CH:18](=O)[CH2:19][CH2:20][CH2:21][CH3:22].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C(Cl)Cl>[CH2:18]([NH:15][C:11]1[CH:10]=[C:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:16])([F:17])[F:1])=[CH:8][CH:7]=2)[CH:14]=[CH:13][CH:12]=1)[CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCC=O
Reactant: Nc1cccc(-c2ccc(C(F)(F)F)cc2)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCCCCNc1cccc(-c2ccc(C(F)(F)F)cc2)c1
Yield: 43.9 %

Procedure:
To a solution of 4′-(trifluoromethyl)-1,1′-biphenyl-3-ylamine (0.3 g, 1.26 mmol) in anhydrous CH2Cl2 (10 mL) under nitrogen at room temperature was added valeraldehyde (0.134 mL, 1.26 mmol), sodium triacetoxyborohydride (0.374 g, 1.76 mmol) and acetic acid (72 μl, 1.26 mmol). The resultant mixture was stirred for 17 h at room temperature. The reaction mixture was quenched with sat. NaHCO3 aq. (15 mL), then extracted with CH2Cl2 (2×20 mL). The organic solution was dried (Na2SO4) and the solvent was removed in vacuo. Purification by SPE (20 g Silica column) eluted with 1:200 EtOAc:cyclohexane afforded the title compound as a colourless oil (0.17 g).
Reaction SMILES: [CH2:1]([NH2:7])[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.[C:8]([NH:15][C@H:16]([C:24](O)=[O:25])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]>>[C:8]([NH:15][C@H:16]([C:24]([NH:7][CH2:1][C:2]1[O:6][CH:5]=[CH:4][CH:3]=1)=[O:25])[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reactant: NCc1ccco1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)NCc1ccco1
Yield: 88.6 %

Procedure:
In substantially the same manner as Working Example 2, furfurylamine (2.91 g) was condensed with Boc-L-phenylalanine (8.75 g) to give N-(Boc-L-phenylalanyl)furfurylamine (9.14 g) (yield 89%). The Boc group of the product was deprotected by using TFA, and 0.43 g of thus-deprotected compound was condensed, in substantially the same manner as Working Example 42, with monoethyl ester of (2S,3S)-N-methylaziridine-2,3-dicarboxylic acid (0.28 g) to give the above-titled compound (Compound 89; 0.23 g) as white crystals (yield 36%).
Reaction SMILES: [C:1]([O-])(=O)C.[Na+].P(Cl)(Cl)(Cl)=O.[CH3:11][C@:12]12[CH2:29][CH2:28][C@H:27]3[C@@H:17]([C:18](=[O:30])[CH:19]=[C:20]4[C@:25]3([CH3:26])[CH2:24][CH2:23][CH2:22][CH2:21]4)[C@@H:16]1[CH2:15][CH2:14][C:13]2=[O:31]>C(Cl)(Cl)Cl.C(OCOCC)C>[CH2:1]=[C:21]1[CH2:22][CH2:23][CH2:24][C@@:25]2([CH3:26])[C:20]1=[CH:19][C:18](=[O:30])[C@@H:17]1[C@@H:27]2[CH2:28][CH2:29][C@@:12]2([CH3:11])[C@H:16]1[CH2:15][CH2:14][C:13]2=[O:31]
Reactant: CC(=O)[O-]
Reactant: C[C@]12CCCCC1=CC(=O)[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCOCOCC
Product: C=C1CCC[C@@]2(C)C1=CC(=O)[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Yield: 80.6 %

Procedure:
A suspension of 1.0 g of sodium acetate in 30 ml of chloroform, 30 ml of formaldehyde diethylacetal, and 3.8 ml of phosphorus oxychloride is combined with 1.0 g of 5-androstene-7,17-dione and refluxed for 61/2 hours. Under agitation, a saturated soda solution is then added dropwise until alkaline reaction occurs in the aqueous phase. The organic phase is separated, washed with water, dried over sodium sulfate, and concentrated under vacuum. The crude product is purified on 200 g of silica gel with a hexane/ethyl acetate gradient (0-50% ethyl acetate), thus isolating 840 mg of 4-methylene-5-androstene-7,17-dione, mp 131.5°-132° C.
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[O:4].[F:13][C:14]1[CH:15]=[C:16]([N:33]2[CH2:37][C@H:36]([CH2:38][N:39]3[CH:43]=[CH:42][N:41]=[N:40]3)[O:35][C:34]2=[O:44])[CH:17]=[CH:18][C:19]=1[C:20]1[CH:21]=[N:22][C:23]([C:26]2[CH2:30][C@@H:29]([CH2:31]O)[O:28][N:27]=2)=[CH:24][CH:25]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:31][C@H:29]1[O:28][N:27]=[C:26]([C:23]2[CH:24]=[CH:25][C:20]([C:19]3[CH:18]=[CH:17][C:16]([N:33]4[CH2:37][C@H:36]([CH2:38][N:39]5[CH:43]=[CH:42][N:41]=[N:40]5)[O:35][C:34]4=[O:44])=[CH:15][C:14]=3[F:13])=[CH:21][N:22]=2)[CH2:30]1)=[O:11])=[O:4]
Reactant: O=C1O[C@@H](Cn2ccnn2)CN1c1ccc(-c2ccc(C3=NO[C@H](CO)C3)nc2)c(F)c1
Reactant: COC(=O)NCCCCC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)NCCCCC(=O)OC[C@@H]1CC(c2ccc(-c3ccc(N4C[C@H](Cn5ccnn5)OC4=O)cc3F)cn2)=NO1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The methyl carbamate prepared as above (0.25 g, 1.43 mmol), (5R)-3-(3-fluoro-4-{6-[(5S) -5-(hydroxymethyl)-4,5-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 1, 0.25 g, 0.57 mmol), 4-dimethylaminopyridine (0.02 g, 0.16 mmol), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.25 g, 1.30 mmol) were combined in DMF (4 ml). The suspension was allowed to stir for one hour at room temperature resulting in a clear solution. The mixture was then diluted with ethyl acetate, washed with water, and dried over magnesium sulfate. The residue obtained upon filtration and evaporation was purified via chromatography (silica gel, 0.5 to 10% methanol in dichloromethane). Evaporation of the product containing fractions and trituration of the resulting solid with diethyl ether yielded the title compound as a white powder (0.33 g), melting point: 90° C.
Reaction SMILES: [C:1]1([CH2:15][OH:16])[C:14]2[C:5](=[CH:6][C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl>[C:1]1([CH:15]=[O:16])[C:14]2[C:5](=[CH:6][C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1
Reactant: OCc1cccc2cc3ccccc3cc12
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=Cc1cccc2cc3ccccc3cc12
Yield: 67.9 %

Procedure:
To a 2 L round bottom flask equipped with condenser and magentic stirring bar was added (1-anthracenyl)methanol (15C, 21.0 g, 0.10 mol), CH2Cl2 (1200 mL) and pyridinium chlorochromate (PCC) (Aldrich, 32.33 g, 0.15 mol). The mixture was then refluxed for 5 h. The reaction was cooled and then filtered through a plug of silica gel (400 g) using PhCH3 as eluting solvent. The first 1 L of solution was collected and concentrated to give 16 g of crude product. This material was further purified by preparative HPLC using PhCH3 as eluting solvent. The solvent was removed and the resulting solid recrystallized (PhCH3 /hexane) to give 14.0 g (67%) of 1-anthracenecarbaldehyde mp 130°-131.5°, (C, H), (lit. mp 126.5°-127.5°, P. H. Gore J. Chem. Soc. 1616 (1959)).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Si:15]([CH3:23])([CH3:22])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:10]=1)C1C=CC=CC=1.O.[H][H]>[Pd].C(O)C>[CH3:22][Si:15]([CH3:23])([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:11]1[CH:10]=[C:9]([OH:8])[CH:14]=[CH:13][CH:12]=1
Reactant: [H][H]
Reactant: CCCCCC[Si](C)(C)c1cccc(OCc2ccccc2)c1
Agent: [Pd]
Solvent: O
Solvent: CCO
Product: CCCCCC[Si](C)(C)c1cccc(O)c1

Procedure:
A mixture of 34.8 g. (0.107 mole) of 1-benzyloxy-3-(dimethyl-hexylsilyl)benzene, 2.0 g. of a 1:1 mixture by weight to volume of 5% by weight palladium on carbon and water, and 100 ml. ethanol was stirred under 1 atm. hydrogen at 25° C. until hydrogen uptake ceased (after an uptake of 2.5 liters). The reaction was filtered through Supercel with ethanol and the filtrate evaporated to a quantitative yield of the title compound as an oil.