(1S,2R)-(-)-1-Amino-2-indanol → (R)-N-[(1R)-1-(7-bromoquinolin-2-yl)ethyl]-2-methylpropane-2-sulfinamide

HRID 2285411Notes

Reaction equation

HRID 2285411 reaction equation
C1C2C(=CC=CC=2)[C@H](N)[C@@H]1O.[Br:12][C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][C:19](/[C:23](=[N:25]/[S@@:26]([C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])/[CH3:24])=[N:20]2)=[CH:15][CH:14]=1.CC(C)([O-])C.[K+]>CC(O)C.C([C@@H]1NC(=O)[C@H](C)[C@H](OCC(F)(F)F)CCC=CC2=CC(=CC=C2)[C@@H](C)NC(=O)[C@H]2NN(CCC2)C(=O)[C@H](C)NC1=O)(C)C>[Br:12][C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][C:19]([C@H:23]([NH:25][S@@:26]([C:28]([CH3:29])([CH3:31])[CH3:30])=[O:27])[CH3:24])=[N:20]2)=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 9866743(1S,2R)-(-)-1-Amino-2-indanolHCID 23665647Potassium tert-butoxideHCID 89949697(NE,R)-N-[1-(7-bromoquinolin-2-yl)ethylidene]-2-methylpropane-2-sulfinamide

Product 1

HCID 89945408(R)-N-[(1R)-1-(7-bromoquinolin-2-yl)ethyl]-2-methylpropane-2-sulfinamideYield 64%

Reagents, catalysts & solvents 2

HCID 89945140(E)-(2R,5S,11 S,14S,17R,18R)-14-Isopropyl-2,11,17-trimethyl-18-(2,2,2-trifluoro-ethoxy)-3,9,12,15,28-pentaaza-tricyclo[21.3.1.1*5,9*]octacosa-1(26),21,23(27),24-tetraene-4,10,13,16-tetraoneCatalystHCID 3776IsopropanolSolvent3×

Conditions

Temperature
90 °C

Procedure

A mixture of (1S,2R)-(−)-cis-1-amino-2-indanol (19 mg, 0.13 mmol), [Ru (p-cymen) Cl2]2 (39 mg, 0.064 mmol) and powdered 4 Å Molecular Sieves (0.7 g) was suspended in anhydrous 2-propanol (3 mL) and stirred under nitrogen. The suspension was heated at 90° C. for 30 minutes. The reaction mixture was cooled to 40° C. and a solution of (R)-2-methyl-propane-2-sulfinic acid [1-(7-bromo-quinolin-2-yl)-eth-(E)-ylidene]-amide (448 mg, 1.27 mmol) in 2-propanol (9 mL) was added followed by a solution of potassium tert-butoxide (36 mg, 0.32 mmol) in 2-propanol (3 mL). The reaction mixture was stirred for 2 hours at 40° C. and then allowed to cool. The mixture was poured directly onto a silica gel cartridge and eluted with ethyl acetate. After concentration the residue was further purified by silica gel chromatography using a gradient of iso-hexane/ethyl acetate 1:1 to 0:1 to give the title compound (287 mg, 64%) as a brown gum. 1H NMR (300 MHz, CDCl3) δ 1.33 (s, 9H), 1.60 (d, J=6.7 Hz, 3H), 4.80 (m, 1H), 5.42 (br d, J=4.2 Hz, 1H), 7.42 (d, J=8.5 Hz, 1H), 7.62 (dd, J=8.5, 1.2 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 8.12 (d, J=8.7 Hz, 1H), 8.25 (s, 1H). LCMS (m/z) 354.9/356.8 [M+H], Tr 2.49 min

Workup

  1. temperatureThe reaction mixture was cooled to 40° C.
  2. stirringThe reaction mixture was stirred for 2 hours at 40° C.
  3. temperatureto cool
  4. additionThe mixture was poured directly onto a silica gel cartridge
  5. washeluted with ethyl acetate
  6. concentrationAfter concentration the residue
  7. customwas further purified by silica gel chromatography

Sources & evidence

ORD record
ord-6dc891bf084b4731a5d3dd1505f500b8
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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