Potassium Carbonate → 5-[3-({[(1S)-1,2-Dimethylpropyl]amino}methyl)phenyl]-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

HRID 656096

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]1.[CH:22]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)=O.C([O-])([O-])=O.[K+].[K+].[BH3-]C#N.[Na+].[CH3:43][CH:44]([CH3:48])[C@@H:45]([NH2:47])[CH3:46]>O1CCOCC1.O.CS(C)=O.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.[Cl-].[Zn+2].[Cl-]>[CH3:46][C@H:45]([NH:47][CH2:22][C:24]1[CH:25]=[C:26]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:14]2[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]2)[CH:27]=[CH:28][CH:29]=1)[CH:44]([CH3:48])[CH3:43]

Participants

Conditions

Temperature: 100 °C

Procedure

To 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (80 mg, 0.216 mmol) in dioxane and water (4 mL/1 mL) was added (3-formylphenyl)boronic acid (45 mg), Pd(PPh3)4 (25 mg) and K2CO3 (104 mg). The reaction mixture was redissolved in DMSO (2 mL). To the resultant mixture zinc chloride (30 mg), NaCNBH3 (30 mg) and (2s)-3-methyl-2-butanamine (50 mg) were added. The mixture was heated to 100° C. for 30 minutes by microwave irradiation and purified by HPLC with TFA to afford the title compound (16 mg).

Workup

custompurified by HPLC with TFA

Sources & evidence

ORD record: ord-1cd909fa55e74deea38760edf410ee6c
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071584B2

Linked notes

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