Diisopropylethylamine → methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester

HRID 470720

Reaction equation

HRID 470720 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:20])[CH2:9][C:10]#[C:11][C:12]1[S:13][CH:14]=[C:15]([C:17]([OH:19])=O)[N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[CH3:63][NH:64][C@H:65]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[CH2:68][CH2:67][CH2:66]1>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:20])[CH2:9][C:10]#[C:11][C:12]1[S:13][CH:14]=[C:15]([C:17](=[O:19])[N:64]([CH3:63])[C@H:65]2[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[CH2:68][CH2:67][CH2:66]2)[N:16]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7128544(R)-N-Methyl-1,2,3,4-tetrahydronaphthalen-1-amineHCID 672524842-[3-(Tert-butoxycarbonyl-methyl-amino)-prop-1-ynyl]-thiazole-4-carboxylic acidHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

Product 1

HCID 67252656methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl esterYield 61.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[3-(tert-butoxycarbonyl-methyl-amino)-prop-1-ynyl]-thiazole-4-carboxylic acid (1.11 g, 3.75 mmol) in DMF (20 mL) was added diisopropylethylamine (1.93 mL, 11.3 mmol), followed by 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1.57 g, 4.13 mmol). After stirring 15 min at RT, (1R)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (0.60 g, 3.75 mmol) was added to the reaction mixture. After stirring overnight at RT, solvent was evaporated and the resulting brown oil was dissolved in ethylacetate (30 mL), washed with saturated aqueous sodium bicarbonate solution (50 mL), 1M HCl solution (50 mL), and brine (50 mL). The organic layer was dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 2:8 to 3:7) to give methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydronaphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester (1.01 g, 61%). 1H-NMR (400 MHz, CDCl3): δ=7.75 (s, 1H (conformers)), 7.03-6.92 (m, 4H), 5.58-5.46 (m, 1H (conformers)), 4.18-4.09 (br, 2H), 2.75 (s, 3H (conformers)), 2.61 (s, 3H), 2.11-1.63 (m, 6H), 1.33 (s, 9H (conformers)). MS: m/z=462 (M+23).

Workup

  1. stirringAfter stirring overnight at RT
  2. customsolvent was evaporated
  3. dissolutionthe resulting brown oil was dissolved in ethylacetate (30 mL)
  4. washwashed with saturated aqueous sodium bicarbonate solution (50 mL), 1M HCl solution (50 mL), and brine (50 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 2:8 to 3:7)

Sources & evidence

ORD record
ord-27e4ff0ae52a4ff49b80ae095ed459b5
Source dataset
uspto-grants-2014_01
Patent number
US08629286B2

Linked notes

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