Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH:13]=[C:12]([C:14]2[N:15]=[C:16]3[C:22]([C:23]([OH:25])=O)=[CH:21][N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:17]3=[N:18][CH:19]=2)[N:11]=[CH:10]1.[NH2:34][C@H:35]([CH:44]1[CH2:46][CH2:45]1)[C:36]([N:38]1[CH2:41][CH:40]([C:42]#[N:43])[CH2:39]1)=[O:37].C(Cl)CCl>CN(C1C=CN=CC=1)C.ClCCl>[C:42]([CH:40]1[CH2:41][N:38]([C:36](=[O:37])[C@H:35]([NH:34][C:23]([C:22]2[C:16]3[C:17](=[N:18][CH:19]=[C:14]([C:12]4[N:11]=[CH:10][N:9]([C:3]5[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=5[F:1])[CH:13]=4)[N:15]=3)[N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[CH:21]=2)=[O:25])[CH:44]2[CH2:45][CH2:46]2)[CH2:39]1)#[N:43]
Reactant: C[Si](C)(C)CCOCn1cc(C(=O)O)c2nc(-c3cn(-c4cc(F)ccc4F)cn3)cnc21
Reactant: N#CC1CN(C(=O)[C@H](N)C2CC2)C1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: ClCCCl
Product: C[Si](C)(C)CCOCn1cc(C(=O)N[C@@H](C(=O)N2CC(C#N)C2)C2CC2)c2nc(-c3cn(-c4cc(F)ccc4F)cn3)cnc21
Yield: 49.7 %

Procedure:
A solution of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.067 g, 0.14 mmol), (R)-1-(2-amino-2-cyclopropylacetyl)azetidine-3-carbonitrile (0.038 g, 0.21 mmol), DMAP (0.021 g, 0.17 mmol) and EDC (0.036 g, 0.19 mmol) in 2 mL dichloromethane was stirred for 13.5 h. Dichloromethane (10 mL) was added, and the solution was sequentially washed with 10 mL of a 1 M citric acid solution, 10 mL of water, and 10 mL of a sat. aq. NaCl solution then dried over Na2SO4, filtered and concentrated. The residue was purified using column chromatography (80% EtOAc/hexanes) to afford 0.044 g (48%) of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a foamy pale yellow solid. MS: (M+Na)+=655.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]([CH3:29])([O:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][C:14]=1[N:22]1[C:26](=[O:27])[N:25]([CH3:28])[N:24]=[N:23]1)[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCO.CC1C=C2N=C3C(=NC(NC3=O)=O)N(C[C@H](O)[C@H](O)[C@H](O)CO)C2=CC=1C>O.[Pd]>[NH2:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][C:10]([CH3:29])([CH3:11])[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[C:14]([N:22]2[C:26](=[O:27])[N:25]([CH3:28])[N:24]=[N:23]2)[CH:15]=1
Reactant: Cn1nnn(-c2cc([N+](=O)[O-])ccc2OC(C)(C)CO[Si](C)(C)C(C)(C)C)c1=O
Agent: [Pd]
Agent: Cc1cc2nc3c(=O)[nH]c(=O)nc-3n(C[C@H](O)[C@H](O)[C@H](O)CO)c2cc1C
Solvent: O
Solvent: CCO
Product: Cn1nnn(-c2cc(N)ccc2OC(C)(C)CO[Si](C)(C)C(C)(C)C)c1=O
Reaction time: 4 h
Yield: 95.7 %

Procedure:
A round-bottom flask was charged with 1-(2-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yloxy)-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (2.54 g, 6.00 mmol), EtOH (60 mL), and 10% Pd/C (50% in water, Degussa type E101; 510 mg, 20 wt % by weight of the starting nitro compound). The flask was sealed with a rubber septum, degassed, and back-filled with H2 (3×) from a balloon filled with H2. The reaction was stirred for 4 h using a H2 filled balloon. The reaction mixture was filtered through a pad of celite, and the pad of celite was rinsed with EtOAc/MeOH. The filtrate was evaporated to dryness to provide 1-(5-amino-2-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yloxy)phenyl)-4-methyl-1H-tetrazol-5(4H)-one (2.26 g, 96%) as a light brown solid that was used without further purification.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[Cl:22])[CH2:14][O:13][C:12]3=[O:23])=[N:7][C:6]=12.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[F:66][C:67]1[CH:72]=[C:71](B2OC(C)(C)C(C)(C)O2)[CH:70]=[CH:69][C:68]=1[C:82]1[N:86]=[CH:85][N:84]([CH2:87][O:88][CH2:89][CH2:90][Si:91]([CH3:94])([CH3:93])[CH3:92])[N:83]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CCOC(C)=O.O1CCOCC1>[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:15]1[CH2:14][O:13][C:12](=[O:23])[N:11]1[C:8]1[CH:9]=[CH:10][N:5]2[N:4]=[CH:3][C:2]([C:71]3[CH:70]=[CH:69][C:68]([C:82]4[N:86]=[CH:85][N:84]([CH2:87][O:88][CH2:89][CH2:90][Si:91]([CH3:93])([CH3:92])[CH3:94])[N:83]=4)=[C:67]([F:66])[CH:72]=3)=[C:6]2[N:7]=1
Reactant: CC1(C)OB(c2ccc(-c3ncn(COCC[Si](C)(C)C)n3)c(F)c2)OC1(C)C
Reactant: O=C1OC[C@H](c2ccccc2Cl)N1c1ccn2ncc(Br)c2n1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: C[Si](C)(C)CCOCn1cnc(-c2ccc(-c3cnn4ccc(N5C(=O)OC[C@@H]5c5ccccc5Cl)nc34)cc2F)n1
Temperature: 80 °C
Reaction time: 2 h
Yield: 30.5 %

Procedure:
To (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-chlorophenyl) oxazolidin-2-one (50 mg, 0.13 mmol) were added Pd2 dba3 (5.8 mg, 0.0064 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.3 mg, 0.013 mmol), 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (69 mg, 0.17 mmol), dioxane (1.2 mL) and 2M Na2CO3 (0.2 mL). The reaction was stirred for 2 hours at 80° C. in a sealed tube. After cooling, EtOAc and water were added. The organic phase was washed with brine and dried over MgSO4. The residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes) to yield (S)-4-(2-chlorophenyl)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (24 mg, 31% yield) as a pale yellow solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([S:16]([CH3:19])(=[O:18])=[O:17])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-])=O.N>CO.[Pd]>[CH3:19][S:16]([N:13]1[CH2:12][CH2:11][N:10]([C:7]2[CH:8]=[CH:9][C:4]([NH2:1])=[CH:5][CH:6]=2)[CH2:15][CH2:14]1)(=[O:17])=[O:18]
Reactant: CS(=O)(=O)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Agent: [Pd]
Agent: N
Solvent: CO
Product: CS(=O)(=O)N1CCN(c2ccc(N)cc2)CC1
Reaction time: 3 h
Yield: 27.5 %

Procedure:
4-(4-Nitrophenyl)-1-methylsulfonylpiperazine (3.83 g, 13.4 mmol), as prepared in Reference Example 12a above, was mixed in methanol (100 ml) and 2 M ammonia in methanol (50 ml) and 10% palladium on carbon (400 mg) was added. The mixture was hydrogenated on a Paar apparatus (50 psi) for 3 h. The reaction was allowed to cool, the catalyst was filtered, washed with methanol then washed with chloroform. The chloroform portion contained a minor amount of the desired but looked purer. The chloroform portion was concentrated in vacuo and was recrystallized ethyl acetate to give 4-[4-(methylsulfonyl)-1-piperazinyl]benzenamine as a shiny brown solid (0.94 g, 27% yield, mp 192–193° C.). GC/MS (EI, M+) m/z=255.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:25]([OH:27])=O)[CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[CH2:17][O:16][C:15]2=[O:24])[CH2:10][CH2:9]1.Cl.[NH2:29][C@H:30]([C:35]([NH2:37])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33]>>[NH2:37][C:35]([C@@H:30]([NH:29][C:25]([C:4]1[CH:5]=[N:6][C:7]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][O:16][C:15]3=[O:24])[CH2:10][CH2:9]2)=[C:2]([Cl:1])[CH:3]=1)=[O:27])[CH2:31][CH:32]([CH3:34])[CH3:33])=[O:36]
Reactant: O=C(O)c1cnc(N2CCC(N3C(=O)OCc4ccccc43)CC2)c(Cl)c1
Reactant: CC(C)C[C@H](N)C(N)=O
Agent: Cl
Product: CC(C)C[C@H](NC(=O)c1cnc(N2CCC(N3C(=O)OCc4ccccc43)CC2)c(Cl)c1)C(N)=O

Procedure:
The title compound was prepared from the product of example 148 step (i) (0.15 g) and (S)-leucinamide hydrochloride (0.07 g) according to the method of example 115, step (i). Yield 0.04 g as a solid.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[CH:18][C:19](CC(NCC4C=CC=CC=4)=O)=[N:20][CH:21]=3)=[CH:12][CH:11]=2)[CH2:3][CH2:2]1.BrC1C=CC(OCCN2CCOCC2)=CC=1.B(O)(O)C1C=CC([F:56])=NC=1>>[F:56][C:19]1[N:20]=[CH:21][C:16]([C:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[CH:11][CH:12]=2)=[CH:17][CH:18]=1
Reactant: OB(O)c1ccc(F)nc1
Reactant: O=C(Cc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1)NCc1ccccc1
Agent: Brc1ccc(OCCN2CCOCC2)cc1
Product: Fc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1

Procedure:
In another aspect, the invention relates to the process for preparing 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide comprising the steps of coupling 4-(2-(4-bromophenoxy)ethyl)morpholine with 6-fluoropyridin-3-yl-3-boronic acid to yield 4-(2-(4-(6-fluoropyridin-3-yl)phenoxy)ethyl)morpholine; reacting 4-(2-(4-(6-fluoropyridin-3-yl)phenoxy)ethyl)morpholine with acetonitrile to yield 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetonitrile; converting 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetonitrile to methyl 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetate; and reacting methyl 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetate with benzylamine to yield 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][C@H:18]3[CH3:30])=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.Cl.O1CCOCC1>CO>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C@H:18]3[CH3:30])=[CH:15][N:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
Reactant: C[C@@H]1CN(C(=O)OC(C)(C)C)CCN1c1ccc(Nc2cc(Br)cn(C)c2=O)nc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: C[C@@H]1CNCCN1c1ccc(Nc2cc(Br)cn(C)c2=O)nc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 94.4 %

Procedure:
To a mixture of 151c (600 mg, 1.26 mmol) in methanol (20 mL) was added HCl/dioxane (4M, 4 mL). The reaction mixture was stirred at room temperature for 4 h. It was then concentrated under reduced pressure. The residue was basified with aqueous 1M NaOH and extracted with dichloromethane (3×30 mL). The combined organic layer was washed with brine and concentrated under reduced pressure to afford 151d (450 mg, 95%) as yellow solid. MS-ESI: [M+H]+ 378.
Reaction SMILES: BrCCCCCCC(OCC)=O.[CH3:13][CH:14]([CH2:20][CH2:21][CH2:22][CH2:23]I)[CH2:15][C:16]([O:18]C)=[O:17].COC(CC(C)CCCCC(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=O.C(OC(CCCCC)CCCC(CCCCC(C)CC(OC)=O)(C([O-])=O)C(OC(C)(C)C)=O)(=O)C.C(C(CCCC(OC(=O)C)CCCCC)CCCCC(C)CC(OC)=O)(O)=O.[C:114]([CH:117]([CH2:129][CH2:130][CH2:131][C@@H:132]([O:138]C(=O)C)[CH2:133][CH2:134][CH2:135][CH2:136][CH3:137])CCCCCCC(OCC)=O)(=[O:116])[NH2:115].C(C(CCCCCC(C(=O)N)CCC[C@@H](O)CCCCC)C(O)=O)C>>[C:114]([CH:117]([CH2:129][CH2:130][CH2:131][CH:132]([OH:138])[CH2:133][CH2:134][CH2:135][CH2:136][CH3:137])[CH2:23][CH2:22][CH2:21][CH2:20][CH:14]([CH3:13])[CH2:15][C:16]([OH:18])=[O:17])(=[O:116])[NH2:115]
Reactant: COC(=O)CC(C)CCCCI
Reactant: CCCCC[C@@H](CCCC(CCCCCCC(=O)OCC)C(N)=O)OC(C)=O
Agent: CCCCCC(CCCC(CCCCC(C)CC(=O)OC)(C(=O)[O-])C(=O)OC(C)(C)C)OC(C)=O
Agent: CCCCCC(CCCC(CCCCC(C)CC(=O)OC)C(=O)O)OC(C)=O
Agent: CCCCC[C@H](O)CCCC(CCCCCC(CC)C(=O)O)C(N)=O
Product: CCCCCC(O)CCCC(CCCCC(C)CC(=O)O)C(N)=O

Procedure:
The synthesis of this compound is carried out as described in Example 1 except that, in Step A, the ethyl 7-bromoheptanoate is replaced by an equimolar amount of methyl 3-methyl-7-iodoheptanoate. The product of Step A is thus: di-tert.-butyl (6-methoxycarbonyl-5-methylhexyl)malonate. Subsequent steps yield: di.-tert.-butyl 2-(4-acetoxynonyl)-2-(6-methoxycarbonyl-5-methylhexyl)malonate (D); methyl 8carboxy-12-acetoxy-3-methylheptadecanoate (V); methyl 8-chlorocarbonyl-12-acetoxy-3-methylheptadecanoate (D); methyl 8-carbamoyl-12-acetoxy-3-methylheptadecanote (E); and 8carbamoyl-12-acetoxy-3-methylheptadecanoic acid (F).
Reaction SMILES: C([SiH](CC)CC)C.O[CH:9]([C:20]1[S:34][C:23]2[C:24]([CH2:30][CH:31]([CH3:33])[CH3:32])=[N:25][N:26]([CH3:29])[C:27](=[O:28])[C:22]=2[CH:21]=1)[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1.FC(F)(F)C(O)=O>ClCCl>[CH3:29][N:26]1[C:27](=[O:28])[C:22]2[CH:21]=[C:20]([CH2:9][C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:13]=[CH:12][CH:11]=3)[S:34][C:23]=2[C:24]([CH2:30][CH:31]([CH3:33])[CH3:32])=[N:25]1
Reactant: CC(C)Cc1nn(C)c(=O)c2cc(C(O)c3cccc4ccccc34)sc12
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)Cc1nn(C)c(=O)c2cc(Cc3cccc4ccccc34)sc12
Reaction time: 0.5 h
Yield: 87 %

Procedure:
Triethylsilane (0.3 ml) was added to a solution of 2-[1-hydroxy-1-(1-naphthalenyl)methyl]-5-methyl-7-(2-methylpropyl)thieno[2,3-d]pyridazin-4(5H)-one (0.3 g) prepared as described in Example 6 above and trifluoroacetic acid (2 ml) in dichloromethane (10 ml). After 30 minutes, the reaction mixture was evaporated and the residue remaining was dissolved in ethyl acetate. The ethyl acetate solution was washed twice with saturated sodium hydrogen carbonate solution and once with brine, and then dried and evaporated. Purification by chromatography eluting with iso-hexane/ethyl acetate (4:1 to 2:1), and subsequent HPLC eluting with isohexane:ethyl acetate (2:1) gave the title compound (0.25 g).
Reaction SMILES: [CH3:1][CH:2]1[CH2:17][CH2:16][O:15][C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[CH3:18][CH:19]1CCOC(=O)CCCCCCOCC1>>[CH3:1][CH:2]1[CH2:17][CH2:16][O:15][C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:19][CH2:18][O:5][CH2:4][CH2:3]1
Reactant: CC1CCOCCCCCCCC(=O)OCC1
Reactant: CC1CCOCCCCCCC(=O)OCC1
Product: CC1CCOCCCCCCCCCC(=O)OCC1

Procedure:
Odor: Animalic, musk, sweet, erogenous, warm-powdery.--IR (film): ν=1735 cm-1 (νC=O), 1117/1151 cm-1 (νasO--C--C), 1254 cm-1 (νasC--C(=O)--O), 1361 cm-1 (δCH3), 1060 cm-1 (νasC--O--C).--1H-NMR (CDCl3): δ=0.92 (d, J=6.8 Hz, 3H, 14-Me), 1.29-1.56 (m, 14H, 4-H2 -9-H2, 13-H2), 1.61-1.67 (m, 3-H2, 15-Hb), 1.79 (ddt, 14.0, 8.4 and 5.2 Hz, 1H, 15-Ha), 1.87 (mc, 1H, 14-H), 2.33 (dd, J=6.8 and 6.0 Hz, 2H, 2-H), 3.34-3.50 (m, 4H, 10-,12-H2), 4.15 (ddd J=11.2, 6.0 and 5.2 Hz, 1H, 16-Hb), 4.18 (ddd, J=11.2, 8.4 and 4.4 Hz, 1H, 16Ha). --13C-NMR (CDCl3): δ=18.54 (q, 14-Me), 24.80/26.15 (t, C-3,-8), 26.17 (d, C-14), 27.31/27.66/27.791/28.22 (t, C-4-C-7), 29.15 (t, C-9), 34.02 (t, C-2), 35.57 (t, C-15), 37.00 (t, C-13), 62.14 (t, C-16), 68.05/70.77 (t, C-10,-12), 174.14 (s, C-1). --MS (EI): m/z (%)=55 (100) [C4H7⊕ ], 83 (71) [C6H11⊕ ], 99 (33) [C6H11O⊕ ]113 (13) [M⊕ --C10H21O]153 (15) [M⊕ --C6H13O2 ], 169 (16) [M⊕ --C6H13O]171 (9) [C10H19O2⊕ ], 227 (1) [M⊕ --C2H3O], 241 (2) [M⊕ --CHO], 270 (1) [M⊕].--C16H30O3 (270.41): calculated C 71.07, H 11.18; found C 71.37, H 11.13.
Reaction SMILES: [CH:1]([C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[C:7]([CH:19]=[CH:20][CH2:21][CH2:22][CH3:23])=[C:6]([CH:24]([CH3:26])[CH3:25])[N:5]=1)([CH3:3])[CH3:2]>C(OCC)(=O)C.CCCCCC>[CH:1]([C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:12]2[CH:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[C:7]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[C:6]([CH:24]([CH3:25])[CH3:26])[N:5]=1)([CH3:3])[CH3:2]
Reactant: CCCC=Cc1c(C(C)C)nc(C(C)C)c(CO)c1-c1ccc(C)cc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CCCCCc1c(C(C)C)nc(C(C)C)c(CO)c1-c1ccc(C)cc1

Procedure:
The title compound was prepared from 2,6-diisopropyl-3-hydroxymethyl-4-(4-methylphenyl)-5-(pent-1-enyl)pyridine (Example 129) by the procedure described in Example 126. 1H NMR (300 MHz, CDCl3): δ 0.77 (t, J=7.0 Hz, 3 H), 1.10-1.40 (m, 19 H), 2.27 (m, 2 H), 2.42 (s, 3 H), 3.22 (m, 1 H), 3.41 (m, 1 H), 4.34 (d, J=6.0 Hz, 2 H), 7.10 (d, J=8.0 Hz, 2 H), 7.20 (d, J=8.0 Hz, 2 H). FAB-MS: calculated for C24H35NO 354; found 354 (M+H, 100%). Rf=0.38 (10% ethyl acetate/n-hexane). mp 92-94° C.
Reaction SMILES: OS(O)(=O)=O.O=S(=O)=O.[N+:10]([O-:13])(O)=[O:11].[OH:14][C:15]1[CH:20]=[C:19]([CH2:21][CH3:22])[N:18]=[CH:17][N:16]=1>>[OH:14][C:15]1[C:20]([N+:10]([O-:13])=[O:11])=[C:19]([CH2:21][CH3:22])[N:18]=[CH:17][N:16]=1
Reactant: CCc1cc(O)ncn1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Product: CCc1ncnc(O)c1[N+](=O)[O-]
Reaction time: 8 h

Procedure:
8 ml of 25% oleum are added dropwise with cooling at a maximum of 10° C. to 8 ml of 100% nitric acid. 12.4 g (0.10 mol) of 4-hydroxy-6-ethylpyrimidine are then introduced in portions at a maximum of 35° C. The temperature is kept at 40° C. overnight. For the purpose of reacting further any starting material that remains, a further 13 ml of 25% oleum and 11 ml of 100% nitric acid are added dropwise at a maximum of 40° C. The mixture is left for 12 hours at 40° C. to complete the reaction and is then poured carefully onto ice and extracted completely with ethyl acetate, and the extracts are washed with sodium hydrogen carbonate solution. The extract is concentrated using a rotary evaporator, whereupon 11.8 g (69.7% of the theoretical yield) of pure substance crystallise out; m.p. 181°-183° C.
Reaction SMILES: C(Cl)CCl.[NH2:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]([OH:16])=O)=[CH:8][CH:7]=1.[CH3:17][N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([CH2:27][NH:28][CH3:29])=[CH:19]1.C1C=CC2N(O)N=NC=2C=1.O.C(N(C(C)C)CC)(C)C>CN(C=O)C>[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([N:28]([CH3:29])[CH2:27][C:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:18]([CH3:17])[CH:19]=2)=[O:16])=[CH:8][CH:7]=1
Reactant: CNCc1cn(C)c2ccccc12
Reactant: Nc1ccc(C=CC(=O)O)cn1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CN(Cc1cn(C)c2ccccc12)C(=O)/C=C/c1ccc(N)nc1
Reaction time: 8 h
Yield: 54.4 %

Procedure:
EDC (0.35 g, 1.89 mmole) was added to a solution of 3-(6-aminopyridin-3-yl)acrylic acid (0.31 g, 1.89 mmole), 1-methyl-3-(methylaminomethyl)-1H-indole (0.30 g, 1.72 mmole), HOBt H2O (0.24 g, 1.89 mmole) and diisopropylethylamine (0.60 mL, 3.44 mmole) in DMF (20 mL) at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine and dried over Na2SO4. Flash chromatography on silica gel (5% MeOH/CHCl3) gave the title compound (0.30 g, 55%) as a light yellow solid: MS (ES) m/e 321 (M+H)+.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14]2[CH:15]=[C:16]([C:21]3[CH:33]=[CH:32][C:24]4[N:25]=[C:26]([NH:28][C:29](=[O:31])[CH3:30])[S:27][C:23]=4[CH:22]=3)[CH:17]=[N:18][C:19]=2[Cl:20])(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>C1COCC1.CO.O.CS(C)=O>[Cl:20][C:19]1[N:18]=[CH:17][C:16]([C:21]2[CH:33]=[CH:32][C:24]3[N:25]=[C:26]([NH:28][C:29](=[O:31])[CH3:30])[S:27][C:23]=3[CH:22]=2)=[CH:15][C:14]=1[NH:13][S:10]([C:7]1[CH:6]=[CH:5][C:4]([CH:1]([OH:3])[CH3:2])=[CH:9][CH:8]=1)(=[O:12])=[O:11]
Reactant: CC(=O)Nc1nc2ccc(-c3cnc(Cl)c(NS(=O)(=O)c4ccc(C(C)=O)cc4)c3)cc2s1
Agent: [BH4-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CO
Solvent: O
Product: CC(=O)Nc1nc2ccc(-c3cnc(Cl)c(NS(=O)(=O)c4ccc(C(C)O)cc4)c3)cc2s1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.6 %

Procedure:
To a solution of N-(6-(5-(4-acetylphenylsulfonamido)-6-chloropyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (0.050 g, 0.10 mmol) in THF (5 mL) and MeOH (5 mL) was added sodium borohydride (0.009 mL, 0.3 mmol) at RT. The resultant was stirred at RT for 1 h, and then diluted with 3 mL of water and 1 mL of DMSO. The resultant was filtered. The filterate was subjected to reverse phase HPLC (5-60% CH3CN in water) purification to give a white solid (30 mg, 60%). MS (ESI pos. ion) Found m/z: 541, (M+K)+.
Reaction SMILES: [CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:38])[C@@H:19]([NH:27]C(=O)OCC2C=CC=CC=2)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]>COCCOC.O>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:38])[C@@H:19]([NH2:27])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]
Reactant: C=CCO[C@@H]1C[C@H](NC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)OCc2ccccc2)c2cc(OC)ccc21
Solvent: COCCOC
Solvent: O
Product: C=CCO[C@@H]1C[C@H](NC[C@@H](O)[C@@H](N)Cc2ccccc2)c2cc(OC)ccc21
Temperature: 110 °C
Reaction time: 16 h
Yield: 49 %

Procedure:
Step V (2): A mixture of benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate (700 mg, 1.36 mmol, from step N(1)), Ba(OH)2.H2O (1.46 g, 7.72 mmol), and DME/H2O (18 mL/12 mL) was heated at 110° C. in a sealed tube. After 16 h, cooled to rt, filtered of solid. Rinsed the vessel and filtercake with fresh DME and concentrated the filtrate in vacuo. The crude product was purified by silica-gel column chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform, linear gradient) to provide 255 mg (49% yield) of the title compound. LC-MS (M+H)=383.0; HRMS (M+H)+=383.2332; [α]D +29.84 (c=6.43 mg/mL, methanol); 1H NMR (500 MHz, CDCl3) δ ppm 1.67 (d, 4H) 1.97 (d, J=13.43 Hz, 1H) 2.43-2.54 (m, 1H) 2.60-2.71 (m, 1H) 2.81 (dd, J=11.90, 8.55 Hz, 1H) 2.90-3.05 (m, 2H) 3.10-3.18 (m, 1H) 3.47 (s, 1H) 3.57 (s, 1H) 3.81 (s, 3H) 4.02-4.16 (m, 2H) 4.77 (dd, J=6.10, 3.97 Hz, 1H) 5.18 (dd, J=10.38, 1.53 Hz, 1H) 5.31 (dd, J=17.24, 1.68 Hz, 1H) 5.96 (dd, 1H) 6.85 (dd, J=8.24, 2.44 Hz, 1H) 6.95 (d, J=2.14 Hz, 1H) 7.15-7.35 (m, 6H).
Reaction SMILES: [OH:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[OH:17])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[CH:2]1([C:11]2[CH:10]=[CH:9][C:8]3[CH2:7][C:6]4[C:15](=[C:2]([OH:1])[CH:3]=[CH:4][CH:5]=4)[C:14](=[O:16])[C:13]=3[C:12]=2[OH:17])[CH2:15][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: O=C1c2c(O)cccc2Cc2cccc(O)c21
Solvent: Cc1ccccc1
Product: O=C1c2c(O)cccc2Cc2ccc(C3CCCCC3)c(O)c21

Procedure:
Mixture of 2-dodecyl- and 4-dodecyl-1,8-dihydroxy-9-(10H)anthracenone, Rf -value: 0.59 (Merck prepared TLC-plates 60F-254; mobile phase: toluene without chamber saturation). For comparison: Rf -value of 1,8-dihydroxy-9-(10H)anthracenone=0.53 (same conditions).