Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].[O:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[CH2:8][CH2:7]1>>[N+:1]([C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[O:6][CH2:7][CH2:8][C:9]2=[O:16])([O-:4])=[O:2]
Reactant: O=[N+]([O-])[O-]
Reactant: O=C1CCOc2ccccc21
Agent: [K+]
Product: O=C1CCOc2c1cccc2[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 2 h
Yield: 9.5 %

Procedure:
A solution of KNO3 (2.25 g, 22.3 mmol) in CH2SO4 (10 mL) was added dropwise to a stirred solution of 4-chromanone (225) (3.0 g, 20.2 mmol) in CH2SO4 (50 mL) at 0° C. and the mixture stirred at 0° C. for 2 h. The mixture was poured into ice/water (500 mL), stirred 30 min and the precipitate filtered. The solid was washed with water (3×10 mL) and dried. The solid was purified by chromatography, eluting with 20% EtOAc/pet. ether, to give (i) 8-nitro-2,3-dihydro-4H-chromen-4-one (226) (369 mg, 9%) as a white solid: mp (EtOAc/pet. ether) 120-121° C.; 1H NMR δ 8.17 (dd, J=7.8, 1.8 Hz, 1H, H-7), 8.10 (dd, J=8.0, 1.8 Hz, 1H, H-5), 7.12 (dd, J=8.0, 7.8 Hz, 1H, H-6), 4.73 (dd, J=6.5, 6.4 Hz, 2H, H-2), 2.95 (br t, J=6.5 Hz, 2H, H-3). Anal. calcd for C9H7NO4: C, 56.0; H, 3.7; N, 7.3. Found: C, 56.1; H, 3.7; N, 7.3%; and (ii) 6-nitro-2,3-dihydro-4H-chromen-4-one (227) (3.17 g, 81%) as a white solid: mp (EtOAc/pet. ether) 169-171° C.; 1H NMR δ 8.78 (d, J=2.8 Hz, 1H, H-5), 8.32 (dd, J=9.1, 2.8 Hz, 1H, H-7), 7.11 (d, J=9.1 Hz, 1H, H-8), 4.67 (dd, J=6.6, 6.4 Hz, 2H, H-2), 2.91 (dd, J=6.6, 6.4 Hz, 2H, H-3); 13C NMR δ 189.4, 165.7, 142.1, 130.3, 123.7, 120.8, 119.3, 67.6, 37.1. Anal. calcd for C9H7NO4: C, 56.0; H, 3.7; N, 7.3. Found: C, 56.1; H, 3.7; N, 7.4%.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]2([CH3:16])[NH:14][C:13](=O)[CH2:12][O:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:26]2)=CC=1>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2([CH3:16])[NH:14][C:13](=[S:26])[CH2:12][O:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC1(c2ccc(F)c(Br)c2)COCC(=O)N1
Solvent: C1CCOC1
Product: CC1(c2ccc(F)c(Br)c2)COCC(=S)N1
Temperature: 70 °C
Reaction time: 2.5 h

Procedure:
A solution of the (RS)-5-(3-bromo-4-fluoro-phenyl)-5-methyl-morpholin-3-one (intermediate X-4) (265 mg, 0.9 mmol) in tetrahydrofuran (5.3 ml) was treated with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's reagent) (380 mg, 0.9 mmol). After 2.5 hours stirring at 70° C. the reaction mixture was evaporated at reduced pressure. The crude product was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100/0 to 0/100 as the eluent. The (RS)-5-(3-bromo-4-fluoro-phenyl)-5-methyl-morpholin-3-thione was obtained as a light yellow gum (262 mg, 94% of theory). MS (ISP): m/z=302.2 [M−H]−, 304.1 [M+2−H]−.
Reaction SMILES: [C:1]([C:4]1[C:5]([N:16]=[CH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][C:8]=1[CH3:9])(=[O:3])[CH3:2].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=1>C(O)C.O>[C:1]([C:4]1[C:5]([N:16]=[CH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[CH:26][CH:27]=2)[C:8]=1[CH3:9])(=[O:3])[CH3:2].[C:1]([C:4]1[C:5]([NH2:16])=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[CH:26][CH:27]=2)[C:8]=1[CH3:9])(=[O:3])[CH3:2]
Reactant: CC(=O)c1c(C)[nH]c(-c2ccccc2)c1N=Cc1ccccc1
Reactant: ClCc1ccc(Cl)cc1
Solvent: CCO
Solvent: O
Product: CC(=O)c1c(N)c(-c2ccccc2)n(Cc2ccc(Cl)cc2)c1C
Product: CC(=O)c1c(N=Cc2ccccc2)c(-c2ccccc2)n(Cc2ccc(Cl)cc2)c1C

Procedure:
The 4-acetyl-3-benzylideneamino-1-(p-chlorobenzyl)-5-methyl-2-phenylpyrrole is prepared from the compound of Example 46 and p-chlorobenzyl chloride by procedure (a) of Example 49, m.p. 136°-37° C. (from ethanol/water). This compound is hydrolyzed as in procedure (b) of Example 49. Yield of the title compound: 58%, m.p. 164°-66° C. (from ethanol/water).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5](O)=[O:6].Cl.[CH3:15][N:16](C)CCCN=C=NCC.CN>C(Cl)Cl.CO>[CH3:15][NH:16][C:5](=[O:6])[C:4]1[CH:8]=[CH:9][C:10]([N+:11]([O-:13])=[O:12])=[C:2]([F:1])[CH:3]=1
Reactant: CCN=C=NCCCN(C)C
Reactant: O=C(O)c1ccc([N+](=O)[O-])c(F)c1
Agent: CN
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CNC(=O)c1ccc([N+](=O)[O-])c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
To a solution of 3-fluoro-4-nitrobenzoic acid (4.0 g, 21.6 mmol) and EDC (1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride) (4.36 g, 28.1 mmol) in methylene chloride (100 mL) was added methylamine (11.3 mL of a 2 M solution in MeOH, 22.7 mmol) and the solution was stirred at room temperature overnight. The solution was washed with 1 N HCl, dried over MgSO4 and concentrated to a solid. The solid was triturated with butyl chloride and collected by filtration to give the N-methyl-3-fluoro-4-nitrobenzamide (3.81 g, 96%).
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].C(Cl)(=O)C(Cl)=O.Cl.[NH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].C(N(C(C)C)CC)(C)C>>[C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7]([NH:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:9])(=[O:3])[CH3:2]
Reactant: CC(=O)SCC(Cc1ccccc1)C(=O)O
Reactant: CCOC(=O)CCN
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCNC(=O)C(CSC(C)=O)Cc1ccccc1

Procedure:
2-Acetylthiomethyl-3-phenylpropanoic acid is reacted with oxalyl choride and the resulting acid chloride is then reacted with β-alanine, ethyl ester, hydrochloride in the presence of diisopropylethylamine as more fully described in Example 1 of European Patent Application 136,883 to give (±)-3-[[2-[(acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]propanoic acid, ethyl ester.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11](O)=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[OH:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:26]=[CH:25][C:22](C=O)=[CH:21][CH:20]=1.N1CCCCC1.CC(N(C)C)=O>O>[OH:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:26]=[CH:25][C:22](/[CH:11]=[CH:10]/[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)=[CH:21][CH:20]=1
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])cc1
Reactant: O=Cc1ccc(OCCCO)cc1
Solvent: C1CCNCC1
Solvent: CC(=O)N(C)C
Solvent: O
Product: O=[N+]([O-])c1ccc(/C=C/c2ccc(OCCCO)cc2)cc1
Temperature: 80 °C
Reaction time: 18 h

Procedure:
4-Nitrophenylacetic acid (131.4 g, 0.73 mole), 4-(3-hydroxypropyloxy)benzaldehyde (130.8 g, 0.73 mole, prepared as in U.S. Pat. No. 2,824,084), piperidine (14.2 g, 0.17 mole) and dimethylacetamide were placed in a 1 L round-bottom flask fitted with a mechanical stirrer, a condenser and a thermometer connected to a controller and a heating mantle. The resulting mixture was stirred and warmed to 80° C., at which temperature a brisk evolution of gas was induced. Stirring was continued at 80° C. for 18 h. The mixture was then poured into a beaker and stirred and diluted to 3 L with ice and water. The solid that appeared was collected by filtration, washed with water and dried to give a deep yellow product (142 g). Two crystallizations from aqueous ethanol afforded the analytical sample (76.9 g, 35%).
Reaction SMILES: [CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([CH2:10][OH:11])[CH2:6][CH2:5]1)[C:2]#[CH:3].C(OC1C(OC(=O)C)=C(I)C=CC=1)(=[O:14])C.CC1(C)N([O])C(C)(C)CCC1>C(#N)C.O>[CH2:1]([CH:4]1[CH2:9][CH2:8][CH:7]([C:10]([OH:14])=[O:11])[CH2:6][CH2:5]1)[C:2]#[CH:3]
Reactant: C#CC[C@H]1CC[C@H](CO)CC1
Reactant: CC(=O)Oc1cccc(I)c1OC(C)=O
Agent: CC1(C)CCCC(C)(C)N1[O]
Solvent: O
Solvent: CC#N
Product: C#CCC1CCC(C(=O)O)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 95.1 %

Procedure:
To a suspension of Compound 9 (2.45 g, 16 mmol) in 50% acetonitrile/water (35 mL) cooled to 0° C. was added bis-acetoxy-iodobenzene (BAIB) (11.4 g, 35 mmol) and TEMPO (502 mg, 3.2 mmol). The reaction mixture was stirred at 0° C. for 1 hour, then for 90 minutes at room temperature. The solvents were evaporated, and the residue dissolved in 1/1 CH3CN/H2O (100 mL). Once again the solvents were evaporated, and this procedure repeated to remove iodobenzene as its azeotrope. The resulting Compound 11 (2.53 g, 95%) was obtained as a brown sticky solid that was not further purified but carried forward into the next step. 1H-NMR (600 MHz, CD3OD): 1.13 (dq, 2H), 1.45 (dq, 2H), 1.48 (m, 1H), 1.93 (dd, 2H), 2.03 (dd, 2H), 2.12 (dd, 2H), 2.2-2.3 (m, 2H).
Reaction SMILES: Br[CH2:2][C:3](=O)[CH2:4][CH2:5][C:6]([O:8][CH3:9])=[O:7].O.[C:12](=[S:15])([S-:14])[NH2:13].[NH4+]>C(O)C>[CH3:9][O:8][C:6]([CH2:5][CH2:4][C:3]1[N:13]=[C:12]([SH:15])[S:14][CH:2]=1)=[O:7]
Reactant: NC(=S)[S-]
Reactant: COC(=O)CCC(=O)CBr
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COC(=O)CCc1csc(S)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 51.5 %

Procedure:
To a mixture of methyl 5-bromolevulinate (1.22 g), water (5.2 ml) and ethanol (2.6 ml) was added ammonium dithiocarbamate (642 mg) at room temperature. After stirring at room temperature for 2 hours, the resulting crystal was collected by filtration and washed with a cold mixture of water and ethanol at first and diisopropyl ether (×2) to give 4-(2-methoxycarbonylethyl)-2-mercaptothiazole (0.61 g).
Reaction SMILES: CO.[C:3]([O:7][C:8](=[O:47])[C@@H:9]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:10][CH:11]([O:28][S:29]([C:32]1[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=1)(=[O:31])=[O:30])[C:12](=[O:27])[NH:13][CH2:14][C:15]1[C:20]([O:21][CH3:22])=[CH:19][C:18]([O:23][CH3:24])=[CH:17][C:16]=1[O:25][CH3:26])([CH3:6])([CH3:5])[CH3:4]>CC(O)C>[C:3]([O:7][C:8](=[O:47])[C@@H:9]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:10][C@@H:11]([O:28][S:29]([C:32]1[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=1)(=[O:31])=[O:30])[C:12](=[O:27])[NH:13][CH2:14][C:15]1[C:16]([O:25][CH3:26])=[CH:17][C:18]([O:23][CH3:24])=[CH:19][C:20]=1[O:21][CH3:22])([CH3:6])([CH3:5])[CH3:4]
Reactant: COc1cc(OC)c(CNC(=O)C(C[C@H](NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)OS(=O)(=O)c2ccc(C)cc2)c(OC)c1
Solvent: CC(C)O
Solvent: CO
Product: COc1cc(OC)c(CNC(=O)[C@@H](C[C@H](NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)OS(=O)(=O)c2ccc(C)cc2)c(OC)c1

Procedure:
Following the procedure in the preparation of 11, compound 11′ was prepared from alcohol 10′ (2.010 g, 4.04 mmol) as a pale white foamy solid (2.599 g, 99% yield): [α]26D=−30.5 (c=1.04, MeOH); HPLC of 11′ for purity: 98.0%, [major peak: Rt=15.9 min; minor peaks: 19.0 min and 24.6 min; column: Chiralcel ODH (250×4.6 mm), UV detector, 210 nm, 5% 2-propanol in hexanes; flow rate: 1.0 mL/min]. 1HNMR (200 MHz, CD2Cl2) δ 7.72 (d, 2H, J=8.4 Hz), 7.28 (d, 2H, J=8.2 Hz), 6.73 (br s, 1H), 6.15 (s, 2H), 5.12 (br s, 1H), 4.84 (t, 1H, J=6.0 Hz), 4.39 (dd, 1H, J1=13.9 Hz, J2=5.7 Hz), 4.27 (dd, 1H, J1=13.9 Hz, J2=5.3 Hz), 3.96 (q, 1H, J=7.4 Hz), 3.821 (s, 3H), 3.817 (s, 6H), 2.41 (s, 3H), 2.20 (t, 2H, J=6.4 Hz), 1.43 (s, 9H), 1.42 (s, 9H). 13C NMR (50 MHz, CD2Cl2) δ 170.6, 167.1, 161.2, 159.4, 155.4, 145.5, 132.9, 130.1, 128.1, 106.1, 90.9, 82.1, 79.9, 77.5, 56.0, 55.5, 51.6, 34.8, 32.6, 28.4, 28.1, 21.8. HRMS calcd for C31H45N2O11S (M+H)+: 653.2744. found: 653.2740.
Reaction SMILES: P(Br)(Br)[Br:2].N1C=CC=CC=1.[Cl:11][C:12]1[CH:13]=[C:14]([CH2:21][CH2:22][CH2:23]O)[CH:15]=[C:16]([O:19][CH3:20])[C:17]=1[Cl:18]>C1(C)C=CC=CC=1>[Cl:18][C:17]1[C:12]([Cl:11])=[CH:13][C:14]([CH2:21][CH2:22][CH2:23][Br:2])=[CH:15][C:16]=1[O:19][CH3:20]
Reactant: BrP(Br)Br
Reactant: COc1cc(CCCO)cc(Cl)c1Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: COc1cc(CCCBr)cc(Cl)c1Cl
Temperature: -5 °C
Reaction time: 0.25 h

Procedure:
In a four-necked flask fitted with a stirrer, internal thermometer, dropping funnel and calcium chloride tube is placed freshly distilled phosphorus tribromide (9.6 g., 0.036 mole) and dry toluene (50 ml.). To this is added dry pyridine (1.5 g.). The mixture is stirred for 15 minutes and then cooled to -5° C. A mixture of the product of Step 2 (23.5 g., 0.1 mole) and pyridine (0.5 g.) in toluene (50 ml.) is added dropwise with stirring at -5° C. to -3° C. over a one hour period. The reaction mixture is stirred at -5° C. to -3° C. for an additional hour and then allowed to warm up to 20°-25° C. The mixture is kept for 48 hours and then added to ice water (ca. 500 ml.). The toluene layer is separated and washed with water, dilute hydrochloric acid, sodium bicarbonate solution and again with water. After drying over Na2SO4 and evaporation of the toluene under reduced pressure there is obtained 2,3-dichloro-5-(3-bromopropyl)anisole.
Reaction SMILES: C([O:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15])CCCCCCCCCCC.[CH:23](O[C:27](=[NH:29])[NH2:28])([CH3:25])[CH3:24].[CH:30](O)([CH3:32])[CH3:31]>>[N:28]#[C:27][NH2:29].[CH2:24]([C:22]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:14]([OH:13])(=[O:15])=[O:16])[CH2:23][CH2:25][CH2:31][CH2:30][CH2:32][CH2:21][CH2:22][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCCCCOS(=O)(=O)c1ccccc1
Reactant: CC(C)OC(=N)N
Reactant: CC(C)O
Product: CCCCCCCCCCCCc1ccccc1S(=O)(=O)O
Product: N#CN

Procedure:
Furthermore, in JP-A-62-22751, it is disclosed that O-isopropyl-isourea dodecylbenzene sulfonate is obtained from isopropyl alcohol, cyanamide and dodecylbenzene sulfonic acid at a yield of 97.6%.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH:22]([CH2:43][O:44][C:45]([CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53]/[CH:54]=[CH:55]\[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])=[O:46])[O:23][C:24]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]/[CH:33]=[CH:34]\[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[O:25])=[O:19].C(O)(=O)CCCCCCC/C=C\CCCCCCCC.C(O)(=O)CCCCCCCCCCCCCCCCC.C(O)(=O)CCCCCCCCCCCCCCC>>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH:22]([O:23][C:24]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[O:25])[CH2:43][O:44][C:45]([CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])=[O:46])=[O:19]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(COC(=O)CCCCCCC/C=C\CCCCCCCC)OC(=O)CCCCCCC/C=C\CCCCCCCC
Agent: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCCCC(=O)O
Product: CCCCCCCCCCCCCCCCCC(=O)OCC(COC(=O)CCCCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCCCC

Procedure:
The stearin part of transesterified oil can be obtained by transesterifying a raw oil-and-fat containing 10 to 40% by mass of oleic acid, 10 to 40% by mass of stearic acid and 30 to 70% by mass of palmitic acid, and then fractionating it so as to obtain an olein part, and further fractionating the olein part. It is preferable to use a raw oil-and-fat containing 10 to 35% by mass of oleic acid, 15 to 40% by mass of stearic acid and 35 to 65% by mass of palmitic acid, and it is more preferable to use a raw oil-and-fat containing 10 to 30% by mass of oleic acid, 15 to 35% by mass of stearic acid and 35 to 55% by mass of palmitic acid.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:10]([S:11]([NH2:14])(=[O:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.C[Al](C)C.[CH3:19][O:20][C:21]1[CH:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH:28][C:29](=O)[O:30]C)[N:22]=1.Cl>ClCCCl>[CH3:19][O:20][C:21]1[CH:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH:28][C:29]([NH:14][S:11]([C:10]2[C:4]3[S:3][C:2]([CH3:1])=[N:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)(=[O:13])=[O:12])=[O:30])[N:22]=1
Reactant: Cc1nc2cccc(S(N)(=O)=O)c2s1
Reactant: COC(=O)Nc1nc(C)cc(OC)n1
Agent: C[Al](C)C
Agent: Cl
Solvent: ClCCCl
Product: COc1cc(C)nc(NC(=O)NS(=O)(=O)c2cccc3nc(C)sc23)n1
Temperature: 0 °C
Yield: 17.4 %

Procedure:
A suspension of 1.5 g of the product from Example 9 in 33 mL of 1,2-dichloroethane was cooled to 0° C. under a nitrogen atmosphere and treated with 3.6 mL of trimethylaluminum (2M solution in toluene). The mixture was warmed briefly to 50°-60° C., recooled to room temperature, and treated with 1.4 g of 4-methoxy-6-methylpyrimidin-2-yl-carbamic acid, methyl ester. This reaction mixture was heated at reflux temperature for approximately 48 hours and was then cooled to 0° C. and acidified by the addition of 5% aqueous hydrochloric acid. The resulting precipitate was separated by filtration and washed with water and 1-chlorobutane. The filtrate was dried over magnesium sulfate, treated with carbon, and concentrated in vacuo to give a yellow gum. Crystallization from hot acetonitrile afforded 0.45 g of the title compound as an off-white solid, m.p. 178°-180° C.; NMR (CDCl3): δ 2.5 (3H, s), 2.8 (3 H, s), 3.9 (3H, s), 6.3 (1H, s), 7.5-7.8 (1H, br s), 7.6 (1H, t), 8.2 (2H, br d); IR(KBr): 1710 (carbonyl stretch) cm-1.
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=5)[NH:15][C:14]4=[O:24])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.CC1(C)C(C)(C)OB(/[CH:33]=[CH:34]/[C:35]2[CH:48]=[CH:47][C:38]([CH2:39][CH2:40][N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[CH:37][CH:36]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[CH3:23][O:22][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:24])[C@:13]12[CH2:12][C@H:11]1[C:7]1[CH:6]=[C:5]2[C:10]([C:2]([CH:33]=[CH:34][C:35]3[CH:36]=[CH:37][C:38]([CH2:39][CH2:40][N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)=[CH:47][CH:48]=3)=[N:3][NH:4]2)=[CH:9][CH:8]=1
Reactant: COc1ccc2c(c1)[C@]1(C[C@H]1c1ccc3c(I)n[nH]c3c1)C(=O)N2
Reactant: CC1(C)OB(/C=C/c2ccc(CCN3CCOCC3)cc2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1ccc2c(c1)[C@]1(C[C@H]1c1ccc3c(C=Cc4ccc(CCN5CCOCC5)cc4)n[nH]c3c1)C(=O)N2
Temperature: 25 °C
Yield: 55.2 %

Procedure:
To a mixture of (1R,2S)-2-(3-iodo-1H-indazol-6-yl)-5′-methoxyspiro[cyclopropane-1,3′-indolin]-2′-one (172 mg, 0.4 mmol) and (E)-4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)phenethyl)morpholine (138 mg, 0.4 mmol) in PhCH3/EtOH (8 mL/4 mL) in a 20 mL microwave vial was added 1 M Na2CO3 (0.8 mL, 0.8 mmol), followed by Pd(PPh3)4 (23 mg, 0.02 mmol, 5 mol %). The resulting mixture was purged with argon, then microwaved for 2 h at 125° C. After cooling to rt, the mixture was diluted with H2O (20 mL), extracted with EtOAc (30 mL×2) and dried (Na2SO4). After removal of solvents, the residue was redissolved in DMF (4 mL) and purified by preparatory HPLC to give the title compound (TFA salt, 115 mg, 45%) as a pale yellow solid. 1H NMR (400 MHz, CD3OD) δ 7.90 (d, J=8.4 Hz, 1H), 7.53 (d, J=7.2 Hz, 2H), 7.43 (s, 1H), 7.37 (d, J=6.4 Hz, 2H), 7.28 (d, J=7.2 Hz, 2H), 6.95 (d, J=7.6 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H), 6.57 (d, J=7.6 Hz, 1H), 5.57 (s, 1H), 4.06 (d, J=11.2 Hz, 2H), 3.80 (t, J=11.2 Hz, 2H), 3.56 (d, J=11.2 Hz, 2H), 3.38 (t, J=7.6 Hz, 2H), 3.27-3.12 (m, 5H), 3.07 (t, 2H), 2.20-2.10 (m, 2H); MS ESI 521.4 [M+H]+, calcd for [C32H32N4O3+H]+ 521.2.
Reaction SMILES: [BH4-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=[O:20])[C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[NH:18][CH3:19].O>O1CCCC1>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([OH:20])[C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[NH:18][CH3:19]
Reactant: CNc1ccc(Cl)cc1C(=O)c1ccccc1Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CNc1ccc(Cl)cc1C(O)c1ccccc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.1 %

Procedure:
To a suspension of sodium borohydride (1.2 g) in tetrahydrofuran (10 ml), a solution of 2',5-dichloro-2-methylaminobenzophenone (3.12 g) in tetrahydrofuran (20 ml) is added dropwise. The resultant mixture is mixed with water (5 ml) and stirred at room temperature overnight. The reaction mixture is mixed with a small amount of water and evaporated under reduced pressure to remove the solvent. The residue is made to pH 8-9 with dilute hydrochloric acid and shaken with chloroform. The organic layer is dried and evaporated to give 2',5-dichloro-2-methylaminobenzhydrol (3.05 g). This substance is recrystallized from ether/n-hexane to give crystals melting at 105.5° to 106.5° C. The yield is 97.1%.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[CH3:9][O:10][C:11](=[O:27])[CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][C:20]([OH:26])=[CH:21][CH:22]=2)[CH:17]=1>ClC(Cl)C>[CH3:9][O:10][C:11](=[O:27])[CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[C:19]([C:1](=[O:3])[CH3:2])[C:20]([OH:26])=[CH:21][CH:22]=2)[CH:17]=1
Reactant: CC(=O)Cl
Reactant: COC(=O)CCCOc1ccc2ccc(O)cc2c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: COC(=O)CCCOc1ccc2ccc(O)c(C(C)=O)c2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 29 %

Procedure:
Under argon, 2.8 ml of acetyl chloride was added to a suspension of 5.15 g of aluminum chloride in 120 ml of dichloroethane and then 8 g of 4-[(7-hydroxy-2-naphthalenyl)oxy] butanoic acid methyl ester was added. The resulting mixture was stirred at room temperature for 30 minutes and at reflux for 16 hours. The solution was filtered and the dark residue was broken up with 3N hydrochloric acid and extracted with methylene chloride. The filtrate was combined with the methylene chloride extract, washed and dried to give a black oil which was purified by high pressure liquid chromatography, eluting with 2% ethyl acetate/toluene to yield 2.72 g, (29%) of 4-[(8-acetyl-7-hydroxy-2-naphthalenyl)oxy] butanoic acid methyl ester as an oil.
Reaction SMILES: Br[C:2]1[CH:7]=[N:6][C:5]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][N:3]=1.Cl.[NH2:17][CH2:18][CH2:19][C:20]([CH3:23])([OH:22])[CH3:21].C(N(CC)CC)C>N1C=CC=CC=1>[CH3:21][C:20]([OH:22])([CH2:19][CH2:18][NH:17][C:2]1[CH:7]=[N:6][C:5]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][N:3]=1)[CH3:23]
Reactant: Brc1cnc(C#Cc2ccccc2)cn1
Reactant: CC(C)(O)CCN
Agent: Cl
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: CC(C)(O)CCNc1cnc(C#Cc2ccccc2)cn1
Yield: 509.8 %

Procedure:
A solution of 2-bromo-5-(phenylethynyl)pyrazine (Example 168, step 1) (158 mg, 0.061 mmol) and 4-amino-2-methylbutan-2-ol hydrochloride (255 mg, 1.83 mmol, 30 equiv.) and triethylamine (185 mg, 255 μl, 1.83 mmol, 30 equiv.) in 3 ml pyridine was stirred overnight at 85° C. The reaction mixture was concentrated in vaccuo. After workup with dichloromethane/water/brine, and drying over magnesium sulfate, the organic phases were concentrated in vacuo. The crude product was chromatographed over a prepacked 20 g silica column eluting with a 25% to 100% ethyl acetate in heptane gradient which yielded the title compound (87.5 mg, 51% yield) as an off-white solid, MS: m/e=282.2 (M+H+).
Reaction SMILES: [CH3:1][N:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([NH2:5])=O.C(N(CC)CC)C.O>C(Cl)(Cl)Cl.[OH-].[Na+]>[CH3:1][N:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]#[N:5]
Reactant: CN(Cc1ccccc1)C(N)=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Solvent: O
Product: CN(C#N)Cc1ccccc1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 82.1 %

Procedure:
To N-methyl-N-benzylurea (1.64 g, 0.01 mol) in chloroform (24 ml) and 50% aqueous sodium hydroxide solution (5.4 ml) was added triethylamine (0.1 g, 0.001 mol) and the mixture was vigorously stirred at room temperature for 3.5 h. After addition of water and chloroform, the mixture was stirred, then extracted with chloroform. The extracts were washed with water, dried with anhydrous sodium sulfate, and evaporated under reduced pressure to a residue, which was chromatographed to afford N-methyl-N-benzylcyanamide (1.2 g, 82% yield) as oily substance: NMR(CDCl3)δ 2.77(s, 3H), 4.14(s, 2H), 7.25-7.50(m, 5H); IR(neat) 2220, 1495, 1455, 1365, 730 cm-1.