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

HRID 1891461Notes

Reaction equation

HRID 1891461 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][CH: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>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.COCCOC.O>[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][CH: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 583671525-(5-Bromothiazol-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 58367229(S)-tert-butyl (4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamateYield 83%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

Prepared using General Procedure 4. A solution of 5-(5-bromothiazol-2-yl)-2-fluorobenzonitrile THZ INT-2 (2.0 g, 7.0 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 (2.5 g, 7.0 mmol), potassium carbonate (2.9 g, 21 mmol) and a 3:1 mixture of DME/H2O (30 mL) was degassed with N2 for 10 min before the addition of Pd(PPh3)4 (0.57 g, 0.005 mmol). The mixture was degassed with N2 for an additional 2 min and the suspension was heated under nitrogen at 80° C. for 12 h. Upon cooling, the reaction mixture was diluted with EA (20 mL) and washed with brine (20 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel flash chromatography (30% EA/hexanes) to produce 3.0 g (83%) of (S)-tert-butyl(4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamate as a white solid. LCMS-ESI (m/z) calculated for C24H22FN3O2S: 435.5; found 436.1 [M+H]+, tR=4.14 min. 1H NMR (400 MHz, CDCl3) δ 8.20 (m, 2H), 7.93 (s, 1H), 7.44 (d, J=7.5 Hz, 1H), 7.32 (m, 3H), 5.26 (m, 1H), 4.76 (d, J=8.4 Hz, 1H), 3.09 (m, 2H), 2.65 (ddd, J=12.5, 8.3, 4.6 Hz, 1H), 1.84 (dq, J=12.9, 8.5 Hz, 1H), 1.48 (s, 9H).

Workup

  1. customPrepared
  2. customThe mixture was degassed with N2 for an additional 2 min
  3. temperatureUpon cooling
  4. additionthe reaction mixture was diluted with EA (20 mL)
  5. washwashed with brine (20 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel flash chromatography (30% EA/hexanes)

Sources & evidence

ORD record
ord-77ec342c72174f8e907eff1d9acfa669
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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