Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:12][C:11](=[O:13])[NH:10][N:9]=2)=[C:4]([NH:14][CH:15]([CH3:17])[CH3:16])[CH:3]=1.[Si:18]([O:25][CH2:26][CH2:27][CH2:28][NH2:29])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C(O)C>[Si:18]([O:25][CH2:26][CH2:27][CH2:28][NH:29][C:11]([NH:10][NH:9][C:8](=[O:12])[C:5]1[C:4]([NH:14][CH:15]([CH3:17])[CH3:16])=[CH:3][C:2]([Cl:1])=[N:7][CH:6]=1)=[O:13])([C:21]([CH3:23])([CH3:24])[CH3:22])([CH3:20])[CH3:19]
Reactant: CC(C)Nc1cc(Cl)ncc1-c1n[nH]c(=O)o1
Reactant: CC(C)(C)[Si](C)(C)OCCCN
Solvent: CCO
Product: CC(C)Nc1cc(Cl)ncc1C(=O)NNC(=O)NCCCO[Si](C)(C)C(C)(C)C
Temperature: 90 °C

Procedure:
5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2(3H)-one (49) (1.2 g, 4 mmol) and 3-((tert-butyldimethylsilyl)oxy)propan-1-amine (48) (7 mmol, 1.5 equiv.) were dissolved in ethanol (5 mL). Refluxed the reaction mixture at 90° C., overnight. The reaction mass was concentrated under reduced pressure to remove excess of solvent. The crude material obtained was taken to next step as such, without purification. LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 1.02 min; LCMS (ES-API), m/z 444.9 (M+H).
Reaction SMILES: [H-].[Na+].[CH3:3][CH:4]([SH:6])[CH3:5].[Br:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[C:10](F)[CH:9]=1.O>CS(C)=O>[Br:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[C:10]([S:6][CH:4]([CH3:5])[CH3:3])[CH:9]=1
Reactant: O=C(O)c1ccc(Br)cc1F
Reactant: CC(C)S
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)Sc1cc(Br)ccc1C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of sodium hydride (32.87 g) in dimethyl sulfoxide (600 ml) was added 2-propanethiol (41.73 ml) at ° C. under nitrogen atmosphere and stirred at room temperature for 1 hour. The reaction mixture was cooled with ice bath and added 4-bromo-2-fluorobenzoic acid (60 g). The reaction mixture was stirred at 70° C. for 1.5 hours and then cooled to room temperature. The mixture was poured into water (3 l) and washed with hexane (600 ml). The water layer was acidified with concentrated hydrochloric acid and then the resulting white solid was collected by filtration. The white solid was dried at 60° C. to give 4-bromo-2-(isopropylthio)benzoic acid (75.49 g).
Reaction SMILES: Cl[C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)=[C:10]([Cl:24])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:25]([C:37]3[N:41]([CH3:42])[CH:40]=[N:39][CH:38]=3)([C:27]3[CH:28]=[N:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=3)[OH:26])[CH:8]=2)[N:3]=1.Cl.[CH3:44][O:45][CH:46]1[CH2:49][NH:48][CH2:47]1.CN(C=O)C>CCOC(C)=O>[Cl:24][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:25]([C:37]3[N:41]([CH3:42])[CH:40]=[N:39][CH:38]=3)([C:27]3[CH:28]=[N:29][C:30]([C:33]([F:35])([F:36])[F:34])=[CH:31][CH:32]=3)[OH:26])[CH:8]=2)[N:3]=[C:2]([N:48]2[CH2:49][CH:46]([O:45][CH3:44])[CH2:47]2)[C:11]=1[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH:23]=[CH:22][CH:21]=[N:20]2)=[CH:17][CH:18]=1
Reactant: COC1CNC1
Reactant: Cn1cncc1C(O)(c1ccc(C(F)(F)F)nc1)c1ccc2nc(Cl)c(Cc3ccc(-n4cccn4)cc3)c(Cl)c2c1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC1CN(c2nc3ccc(C(O)(c4ccc(C(F)(F)F)nc4)c4cncn4C)cc3c(Cl)c2Cc2ccc(-n3cccn3)cc2)C1
Temperature: 100 °C

Procedure:
{2,4-Dichloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)pyrimidin-2-ylmethanol (200 mg, 0.328 mmol, Intermediate 65), 3-methoxyazetidine hydrochloride (427 mg, 3.28 mmol), and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature overnight. The reaction vessel was then cooled to room temperature and the contents were transferred to a separatory funnel with EtOAc dilution, and extracted once with saturated, aqueous NH4Cl solution, then extracted three times with deionized water. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to provide the title compound. MS (ESI): mass calcd. for C34H29ClF3N7O2, 659.2. m/z found, 660.3 [M+H]+. 1H NMR (600 MHz, CD3OD) δ ppm 8.78 (d, J=2.1 Hz, 1H), 8.11 (dd, J=2.5, 0.4 Hz, 1H), 8.07 (d, J=2.1 Hz, 1H), 8.01 (dd, J=8.2, 2.1 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 7.77-7.73 (m, 2H), 7.67 (d, J=1.4 Hz, 1H), 7.62-7.59 (m, 2H), 7.59-7.56 (m, 1H), 7.17 (d, J=8.7 Hz, 2H), 6.49-6.46 (m, 1H), 6.37 (s, 1H), 4.34-4.29 (m, 4H), 4.19-4.13 (m, 1H), 4.02-3.97 (m, 2H), 3.48 (s, 3H), 3.22 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:21]([NH:23][C:24]([CH3:43])([CH2:34][O:35][Si](C)(C)C(C)(C)C)[CH2:25][O:26][Si](C)(C)C(C)(C)C)=[O:22])=[CH:19][NH:20][C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1>Cl.O1CCOCC1>[OH:26][CH2:25][C:24]([NH:23][C:21]([C:18]1[C:16]2=[N:17][C:12]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH3:11])[N:7]=3)=[CH:13][N:14]=[C:15]2[NH:20][CH:19]=1)=[O:22])([CH3:43])[CH2:34][OH:35]
Reactant: Cn1nc(-c2cnc3[nH]cc(C(=O)NC(C)(CO[Si](C)(C)C(C)(C)C)CO[Si](C)(C)C(C)(C)C)c3n2)c2ccc(F)cc21
Agent: Cl
Solvent: C1COCCO1
Product: Cn1nc(-c2cnc3[nH]cc(C(=O)NC(C)(CO)CO)c3n2)c2ccc(F)cc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 67.6 %

Procedure:
2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-N-(2,2,3,3,6,9,9,10,10-nonamethyl-4,8-dioxa-3,9-disilaundecan-6-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (65 mg, 0.104 mmol) was dissolved in a saturated solution of HCl (g) in dioxane (10 mL). The mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure. The residue was triturated with MeOH then decanted and dried to give N-(1,3-dihydroxy-2-methylpropan-2-yl)-2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (28 mg, 68%).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[CH3:9]C(C)([O-])C.[K+].CS(C)=O.[C:19]([C:21]1[C:22]([NH:38][C:39]2[CH:40]=[C:41]([CH:46]=[CH:47][C:48]=2[CH3:49])[C:42]([NH:44][CH3:45])=[O:43])=N[C:24](S(C)(=O)=O)=[N:25][C:26]=1[N:27]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:28])#[N:20]>C(OCC)(=O)C>[C:19]([C:21]1[C:26]([N:27]([CH2:29][C:30]([CH3:31])([CH3:32])[CH3:33])[CH3:28])=[N:25][C:24]([O:8][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:9][C:22]=1[NH:38][C:39]1[CH:40]=[C:41]([CH:46]=[CH:47][C:48]=1[CH3:49])[C:42]([NH:44][CH3:45])=[O:43])#[N:20]
Reactant: CC(C)(C)[O-]
Reactant: CNC(=O)c1ccc(C)c(Nc2nc(S(C)(=O)=O)nc(N(C)CC(C)(C)C)c2C#N)c1
Reactant: CN1CCC(O)CC1
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CNC(=O)c1ccc(C)c(Nc2cc(OC3CCN(C)CC3)nc(N(C)CC(C)(C)C)c2C#N)c1
Temperature: 60 °C

Procedure:
To a portion of 576 mg of 1-methylpiperidine-4-ol (576 mg; 5 mmol) is added 616 mg of potassium tert.-butoxide (5.5 mmol) followed by 4.0 mL of DMSO. After stirring this mixture at r.t. for 1 h a portion of 1.0 mL of this mixture is added at r.t. to 19 mg of 3-{5-cyano-6-[(2,2-dimethyl-propyl)-methyl-amino]-2-methanesulfonyl-pyrimidin-4-ylamino}-4,N-dimethyl-benzamide (0.043 mmol) on 0.2 mL of DMSO. The mixture was heated at 60° C. for 3 h. At r.t. 5 mL of ethyl acetate is added and the organic layer is washed with brine (1×4 mL). The organic layer is dried (MgSO4), volatiles are removed in vacuo and the product is purified via reversed phase prep. HPLC. (Yield: 18.6 mg; 0.026 mmol; 56%). MS (m/z): 480 (M+H).
Reaction SMILES: C12N(C3C=NC4C(=CC=CC=4)N=3)CC1CCNC2.[C:19]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]([N:27]1[CH2:33][CH:32]2[CH:29]([CH2:30][NH:31]2)[CH2:28]1)=[O:26].Cl[C:41]1[N:46]=[C:45]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:44]=[CH:43][N:42]=1>>[C:19]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]([N:27]1[CH2:33][CH:32]2[CH:29]([CH2:30][N:31]2[C:41]2[N:46]=[C:45]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH:44]=[CH:43][N:42]=2)[CH2:28]1)=[O:26]
Reactant: Clc1nccc(-c2ccccc2)n1
Reactant: O=C(c1ccccc1-c1ccccc1)N1CC2CNC2C1
Agent: c1ccc2nc(N3CC4CCNCC43)cnc2c1
Product: O=C(c1ccccc1-c1ccccc1)N1CC2CN(c3nccc(-c4ccccc4)n3)C2C1

Procedure:
The title compound was prepared in a manner analogous to Intermediate 2, Step A, using Intermediate 19 and 2-chloro-4-phenyl-pyrimidine. MS (ESI) mass calcd. for C28H24N4O, 432.53; m/z found, 433.3 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[N:7]([CH2:21][CH3:22])[CH2:8][CH:9]([OH:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pd]>[C:1]([O:5][C:6](=[O:23])[N:7]([CH2:8][CH:9]([OH:20])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=1)[CH2:21][CH3:22])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCN(CC(O)Cc1ccc([N+](=O)[O-])cc1)C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CCO
Product: CCN(CC(O)Cc1ccc(N)cc1)C(=O)OC(C)(C)C

Procedure:
The [3-(4-amino-phenyl)-2-hydroxy-propyl]-ethyl-carbamic acid tert-butyl ester was prepared by the following procedure: To a stirred solution of 1-allyl4-nitrobenzene (2.85 g, 17.47 mmol; prepared by the procedure of EP 1013636 A, 1999) in dichloromethane (100 mL) at room temperature was added 3-chlorperoxybenzoic acid (6.03 g, 57-86%, Aldrich) and the mixture stirred overnight. The solution was washed with excess aqueous sodium thiosulfate, then with aqueous sodium bicarbonate solution and the organic solution was dried (magnesium sulfate), evaporated, and chromatographed on silica gel giving 1.94 g (62%) of 24-nitorbenzyloxirane as a yellow oil. This oil (0.92 g 5.13 mmol) in methanol was stirred overnight at room temperature with aqueous ethylamine (2 mL, 70% in water, Aldrich). The methanol was removed by evaporation and the residue was dissolved in 1N aqueous hydrochloric acid. The aqueous solution was washed with ether and the aqueous layer was made basic with 4N aqueous sodium hydroxide. Tetrahydrofuran was added to dissolve the solids and di-tert-butyl dicarbonate (1.35 g, 6.16 mmol, Aldrich) was added and the mixture stirred at room temperature for 2 hours. The reaction was extracted with dichloromethane, dried (magnesium sulfate), evaporated and chromatographed on silica gel to give ethyl-[2-hydroxy-3-(4-nitro-phenyl)-propyl]carbamic acid tert-butyl ester as a yellow oil, 1.23 g, 74%. MS(ES) (M+H)+=325. This nitro compound (1.06 g, 3.26 mmol) in ethanol (4 mL) and 10% Palladium on Carbon was hydrogenated at 35 psi for 1.5 hours. The mixture was filtered and evaporated to give [3-(4-amino-phenyl)-2-hydroxy-propyl]-ethyl-carbamic acid tert-butyl ester as a yellow gum, 0.94 g (98%) MS(ES) (M+H)+=295.
Reaction SMILES: C([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[C:18]4[N:19]([N:28]=[CH:29][N:30]=4)[C:20]([C:23]4[CH:24]=[N:25][NH:26][CH:27]=4)=[CH:21][N:22]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)(C)C.Br[CH2:32][C:33]([NH2:35])=[O:34]>>[NH:26]1[CH:27]=[C:23]([C:20]2[N:19]3[N:28]=[CH:29][N:30]=[C:18]3[C:17]([NH:16][C:13]3[CH:12]=[CH:11][C:10]([CH:7]4[CH2:8][CH2:9][N:4]([CH2:32][C:33]([NH2:35])=[O:34])[CH2:5][CH2:6]4)=[CH:15][CH:14]=3)=[N:22][CH:21]=2)[CH:24]=[N:25]1
Reactant: CC(C)N1CCC(c2ccc(Nc3ncc(-c4cn[nH]c4)n4ncnc34)cc2)CC1
Reactant: NC(=O)CBr
Product: NC(=O)CN1CCC(c2ccc(Nc3ncc(-c4cn[nH]c4)n4ncnc34)cc2)CC1

Procedure:
This compound may be prepared using methods as described for Compound 84, using 2-bromoacetamide in step 1. LCMS: Rt=0.81 min (100%), m/z (ESI) 418 (M+H)+.
Reaction SMILES: BrC1C=C2C(=CC=1)N(S(C1C=CC=CC=1)(=O)=O)C(C(OCC)=O)=C2S(Cl)(=O)=O.Cl[S:30]([C:33]1[C:41]2[C:36](=[C:37]([N+:42]([O-:44])=[O:43])[CH:38]=[CH:39][CH:40]=2)[N:35](S(C2C=CC=CC=2)(=O)=O)[C:34]=1[C:54]([O:56]CC)=[O:55])(=[O:32])=[O:31].[O:59]([CH2:66][C@H:67]1[O:72][CH2:71][CH2:70][NH:69][CH2:68]1)[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1>>[N+:42]([C:37]1[CH:38]=[CH:39][CH:40]=[C:41]2[C:36]=1[NH:35][C:34]([C:54]([OH:56])=[O:55])=[C:33]2[S:30]([N:69]1[CH2:70][CH2:71][O:72][C@H:67]([CH2:66][O:59][C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH2:68]1)(=[O:31])=[O:32])([O-:44])=[O:43]
Reactant: CCOC(=O)c1c(S(=O)(=O)Cl)c2cccc([N+](=O)[O-])c2n1S(=O)(=O)c1ccccc1
Reactant: c1ccc(OC[C@@H]2CNCCO2)cc1
Agent: CCOC(=O)c1c(S(=O)(=O)Cl)c2cc(Br)ccc2n1S(=O)(=O)c1ccccc1
Product: O=C(O)c1[nH]c2c([N+](=O)[O-])cccc2c1S(=O)(=O)N1CCO[C@H](COc2ccccc2)C1

Procedure:
Following the procedure described in Steps B and C of Example 2, replacing in Step B ethyl 5-bromo-3-(chlorosulfonyl)-1-(phenylsulfonyl)-1H-indole-2-carboxylate with ethyl 3-(chlorosulfonyl)-7-nitro-1-(phenylsulfonyl)-1H-indole-2-carboxylate and replacing morpholine with (S)-2-(phenoxymethyl)morpholine from Step A of Example 23, the title compound was obtained. ESI+MS: 461.9 [M+H]+.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[CH2:13]([N:20]1[C:24]2([CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[NH:23][CH:22]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:21]1=[O:37])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[CH2:13]([N:20]1[C:24]2([CH2:25][CH2:26][N:27]([S:9]([CH3:8])(=[O:11])=[O:10])[CH2:28][CH2:29]2)[NH:23][CH:22]([CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:21]1=[O:37])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C1C(Cc2ccccc2)NC2(CCNCC2)N1Cc1ccccc1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCC2(CC1)NC(Cc1ccccc1)C(=O)N2Cc1ccccc1

Procedure:
Triethylamine (0.15 ml, 1.78 mmol) and subsequently methanesulfonyl chloride (0.14 ml, 1.78 mmol) were added to a solution of 1,3-dibenzyl-1,4,8-triazaspiro-[4,5]decan-2-one (300 mg, 0.89 mmol) in CH2Cl2 (8.1 ml) with stirring using nitrogen as an inert gas at RT. The reaction mixture was stirred overnight. The organic phase was rendered alkaline using aqueous sodium carbonate solution (20 ml) and the aqueous phase was extracted with CH2Cl2 (15 ml). The combined organic phases were dried over Na2SO4. After filtration, removal of the solvent, and column chromatography, the desired product 1,3-dibenzyl-8-methanesulfonyl-1,4,8-triazaspiro[4,5]decan-2-one was obtained in a yield of 287 mg (77% of theory).
Reaction SMILES: [C:1]1([C:7]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4([NH:36]C(=O)OC(C)(C)C)[CH2:35][CH2:34][CH2:33]4)=[CH:28][CH:27]=3)=[N:24][C:10]3[O:11][CH2:12][C:13]4[N:14]([C:15]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=5)=[N:16][N:17]=4)[C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(C(F)(F)F)=O>ClCCl>[C:1]1([C:7]2[C:25]([C:26]3[CH:27]=[CH:28][C:29]([C:32]4([NH2:36])[CH2:35][CH2:34][CH2:33]4)=[CH:30][CH:31]=3)=[N:24][C:10]3[O:11][CH2:12][C:13]4[N:14]([C:15]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=5)=[N:16][N:17]=4)[C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)-n3c(nnc3-c3ccccn3)CO4)cc2)CCC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)-n3c(nnc3-c3ccccn3)CO4)cc2)CCC1
Reaction time: 0.01 h
Yield: 65.1 %

Procedure:
Tert-butyl (1-(4-(8-phenyl-1-(pyridin-2-yl)-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazin-7-yl)phenyl)cyclobutyl)carbamate (15 mg, 0.026 mmol) was dissolved in dichloromethane (1 ml); TFA (0.5 ml) was added at room temperature and the resulting mixture was stirred for 30 seconds. The solution was immediately concentrated to dryness under reduced pressure. The residue was dissolved in diethyl ether (˜2 ml) and concentrated to dryness under reduced pressure. This was repeated three times. The residue was then slurred in diethyl ether (2 ml) and after settling the supernatant solvent was removed by pipette. This was repeated three times. The residue was then slurred in n-hexane (2 ml) and after settling the supernatant solvent was removed by pipette. This was repeated three times. The remaining solvent was removed under reduced pressure. The resulting residue was purified via preparative HPLC to give the desired product as a white solid (8 mg, 64% yield). LCMS (Method D) RT=0.825 min, M+H+=474. 1H NMR (500 MHz, d6-DMSO): 8.79 (1H, d), 8.44 (1H, bs), 8.13 (1H, s), 8.11-8.05 (1H, m), 7.62-7.59 (1H, m), 7.41 (2H, s), 7.42-7.38 (2H, d), 7.25-7.27 (3H, m), 7.10 (2H, m), 5.71 (2H, s), 2.60-2.51 (4H, m), 2.27-2.19 (1H, m), 1.88-1.76 (1H, m).
Reaction SMILES: I[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[C:4](C(OC)=O)[C:3]=1[O:16][CH3:17].[H-].[Na+].COS([O:25][CH3:26])(=O)=O.O.CN([CH:31]=[O:32])C>CCOCC>[CH3:17][O:16][C:3]1[CH:4]=[C:5]([C:31]([O:25][CH3:26])=[O:32])[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=2[CH:2]=1
Reactant: COS(=O)(=O)OC
Reactant: COC(=O)c1cc2c(c(I)c1OC)CCCC2
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: COC(=O)c1cc(OC)cc2c1CCCC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 61 %

Procedure:
To a solution of methyl 3-hydroxy-5,6,7,8-tetrahydro-1-naphthalenecarboxylate (Example 6 subpart (c)) (1.38 g, 6.69 mmol) in DMF (30 mL) was added NaH (0.32 g, 8.0 mmol). After stirring at room temperature for 1 h, dimethylsulfate (0.76 mL, 8.0 mmol) was added, the mixture stirred at room temperature for 1 h and water and Et2O was added. The separated organic layer was washed with brine, water, dried (MgSO4), filtered and concentrated. Following flash chromatography methyl 3-methoxy-5,6,7,8-tetrahydro-1-naphthalenecarboxylate was obtained as a colorless oil (900 mg, 61%). 1H NMR (CDCl3) δ 7.21 (d, 1H), 6.78 (d, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 2.97 (s, 2H), 2.79 (s, 2H), 1.76 (m, 4H); MS m/z 221.1 (M+H).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O-:11].[Na+].C1C2C(=CC=CC=2)C=CC=1O.[C:24](=[O:26])=[O:25]>O>[OH:11][C:2]1[C:3]([C:24]([OH:26])=[O:25])=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1
Reactant: [O-]c1ccc2ccccc2c1
Reactant: O=C=O
Agent: Oc1ccc2ccccc2c1
Agent: [Na+]
Solvent: O
Product: O=C(O)c1cc2ccccc2cc1O
Reaction time: 3 h

Procedure:
A finishing treatment was carried out continuously, while employing the facilities as shown in the drawing. On an hourly basis, 83 kg of sodium 2-naphtholate, 42 kg of 2-naphthol and 166 kg of a mixture of hydrogenated triphenyls were fed to a stirring tank 1, followed by stirring and suspension. The resulting suspension mixture was supplied at a rate of 291 kg/hr to a reaction vessel 2 maintained at a carbon dioxide pressure of 6 kg/cm2 (G), and a reaction was allowed to proceed at 260° C., with the residence time being kept at 3 hours. The reaction mixture flowing out of the reaction vessel 2 was cooled with a heat exchanger 3, and mixed with water fed at a rate of 420 1/hr in a stirring tank 4, and the resulting mixture was regulated at a temperature of 85° C. and transferred to a separating tank 5, followed by separation into the reaction medium layer and the water layer at 85° C. From the upper reaction medium layer, the 2-naphthol was recovered as sodium naphtholate with use of a recovery apparatus (not shown in the drawing). The lower water layer was adjusted in a pH adjusting tank 6 to a pH 5.5 with dilute sulfuric acid and transferred to an extractor 7, where the 2-naphthol and tar were extracted with 2000 liters of xylene. From the xylene layer, there were recovered the xylene and 2-naphthol by use of a vacuum distillation apparatus (not shown in the drawing). The water layer flowing out of the extactor 7 was transferred to an acid precipitation tank 8, and adjusted to a pH 2.0 with dilute sulfuric acid at 85° C. to perform acid precipitation, whereby there was produced 2-hydroxynaphthalene-3-carboxylic acid at a rate of 44.8 kg/hr. The yield based on sodium 2-naphtholate was 47.7%, and 2-naphthol was recovered at a rate of 37.3 kg/hr, with the selectivity being 99.4%.
Reaction SMILES: [K].[S:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][NH:11][C:12](=[S:15])SC)([OH:5])(=[O:4])=[O:3].[N-:16]=[N+:17]=[N-:18].[Na+]>>[S:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[C:12]([SH:15])=[N:18][N:17]=[N:16]1)([OH:5])(=[O:4])=[O:3]
Reactant: CSC(=S)NCCCCCS(=O)(=O)O
Reactant: [N-]=[N+]=[N-]
Agent: [K]
Agent: [Na+]
Product: O=S(=O)(O)CCCCCn1nnnc1S

Procedure:
Reaction of methyl 5-sulfopentyldithiocarbamate potassium salt with sodium azide as described in Example 7 gave 1-(5-sulfopentyl)tetrazole-5-thiol.
Reaction SMILES: [C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[Br:7][C:8]1[CH:9]=[C:10]2[C:16](N)=[N:15][NH:14][C:11]2=[N:12][CH:13]=1.[N:18]1C=CC=CC=1>>[Br:7][C:8]1[CH:9]=[C:10]2[C:16]([CH:2]([CH2:3][CH3:4])[C:1]([NH2:18])=[O:5])=[N:15][NH:14][C:11]2=[N:12][CH:13]=1
Reactant: Nc1n[nH]c2ncc(Br)cc12
Reactant: CCCC(=O)Cl
Reactant: c1ccncc1
Product: CCC(C(N)=O)c1n[nH]c2ncc(Br)cc12

Procedure:
Butyryl chloride (2.1 ml, 20.7 mmol) was added to a stirred solution of 5-bromo-1H-pyrazolo[3,4-b]pyridin-3-ylamine (4.0 g, 18.8 mmol) in pyridine (50 ml). The solution was heated at reflux for 12 hours then concentrated in vacuo. Addition of water afforded a solid which was filtered and dried to afford the title compound.
Reaction SMILES: [H-].[Na+].CN(C)C=O.[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[NH:14][CH:13]=[CH:12]2.[F:20][CH:21]([F:24])[CH2:22]I>O>[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:22][CH:21]([F:24])[F:20])[CH:13]=[CH:12]2
Reactant: FC(F)CI
Reactant: O=c1[nH]ccc2cc(Br)ccc12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1c2ccc(Br)cc2ccn1CC(F)F
Reaction time: 0.5 h
Yield: 65.1 %

Procedure:
Under nitrogen atmosphere, 44 mg of 60% sodium hydride was added at room temperature to 2 ml solution of dimethylformamide with 49 mg of 6-bromo-2H-isoquinoline-1-one and the mixture was stirred for 30 min. Then, 169 mg of 2,2-difluoroethyliodide was added and stirred at room temperature for 6 hours. Cold water was added to the reaction solution, the products were extracted with chloroform. Chloroform layer was washed with saturated saline solution and dried with anhydrous sodium sulfate. The solvents were distilled outunder reduced pressure, and the residues were separated and purified by thin-layer chromatography (chloroform/methyl alcohol=10/1) to obtain 41 mg of the above compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH2:7][OH:8].N1C=CN=C1.[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH2:7][O:8][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]
Reactant: COc1ccc(Br)cc1CO
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COc1ccc(Br)cc1CO[Si](C)(C)C(C)(C)C
Reaction time: 4 h
Yield: 95.8 %

Procedure:
To a solution of 5-bromo-2-methoxybenzyl alcohol (1.0 g, 4.6 mmol) and imidazole (470 mg, 7.01 mmol) in DMF (15 ml) was added tert-butyldimethylsilyl chloride (1.04 g, 6.91 mmol). The mixture was allowed to stir for 4 h, poured onto water (100 ml) and extracted with ether (3×30 ml). The combined organic phases were washed with water (50 ml), brine (50 ml), dried over sodium sulfate and evaporated under reduced pressure to leave a pale yellow oil. This was purified by chromatography (SiO2, 5% ether/petrol), to give the title compound (1.46 g, 96%) as a colourless oil.