Nitrogen → (S)-tert-butyl (4-(5-(3-cyano-4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

HRID 1891460Notes

Reaction equation

HRID 1891460 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=2)[C:12]#[N:13])=[N:4][N:3]=1.[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C:31]2[C:26](=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1)([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[K+].[K+].N#N>COCCOC.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>[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C:31]2[C:26](=[C:27]([C:2]3[S:6][C:5]([C:7]4[CH:8]=[CH:9][C:10]([F:15])=[C:11]([C:12]#[N:13])[CH:14]=4)=[N:4][N:3]=3)[CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1)([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 583672495-(5-Bromo-1,3,4-thiadiazol-2-yl)-2-fluorobenzonitrileHCID 58367258tert-Butyl (S)-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

Product 1

HCID 58367252(S)-tert-butyl (4-(5-(3-cyano-4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamateYield 100%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Prepared using General Procedure 4. A suspension of 5-(5-bromo-1,3,4-thiadiazol-2-yl)-2-fluorobenzonitrile TDZ INT-3 (1.5 g, 5.3 mmol), (S)-tert-butyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate IND INT-17 (1.9 g, 5.3 mmol) and potassium carbonate (2.2 g, 16 mmol) in DME:H2O (3:1, 70 mL) was degassed with N2 for 20 min before the addition of Pd(PPh3)4 (0.43 g, 0.3 mmol). The mixture was degassed with N2 for an additional 5 min and the suspension was heated under N2 at 85° C. for 12 h. Upon cooling, the reaction mixture was diluted with water (150 mL) and the mixture stirred for 30 min. The resulting solid was filtered, washed with water, and dried under high vacuum to afford 2.3 g (100%) of crude (S)-tert-butyl(4-(5-(3-cyano-4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate as light brown solid which was used in the next experiment without purification. LCMS-ESI (m/z) calculated for C23H21FN4O2S: 436.1; found 459.1 [M+Na]+, tR=4.19 min.

Workup

  1. customPrepared
  2. customThe mixture was degassed with N2 for an additional 5 min
  3. temperatureUpon cooling
  4. additionthe reaction mixture was diluted with water (150 mL)
  5. filtrationThe resulting solid was filtered
  6. washwashed with water
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-1ced1cc1b151420786ac13dc29946438
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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