Water → HCID 59378895, compound

HRID 2201631Notes

Reaction equation

HRID 2201631 reaction equation
P(O)(O)(O)=O.[F:6][C:7]1[CH:8]=[C:9]([S:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH:10]=[C:11]2[C:16]=1[C@H:15](NC)[CH2:14][CH2:13][CH2:12]2.[NH2:27][C:28]([NH2:30])=[O:29].O.[CH3:32]N1CCCC1=O>>[F:6][C:7]1[CH:8]=[C:9]([S:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH:10]=[C:11]2[C:16]=1[C@H:15]([CH2:32][NH:27][C:28]([NH2:30])=[O:29])[CH2:14][CH2:13][CH2:12]2

Participants

5

Reactant 4

HCID 962WaterHCID 1176UreaHCID 13387N-methyl-2-pyrrolidoneHCID 66755621HCID 66755621, compound

Product 1

HCID 59378895HCID 59378895, compoundYield 93.8%

Conditions

Temperature
70 °C

Procedure

(R)-8-Fluoro-6-(3-fluorophenylsulfanyl)-1,2,3,4-tetrahydronaphthalen-1-yl-methylamine phosphate salt was treated with urea (27.5 g) in anhydrous N-methylpyrrolidinone (140 ml) at 100° C. for 18 hours. The reaction was cooled to 70° C. and water (360 ml) was added dropwise while allowing the temperature to decline to room temperature. The resulting solids were collected and washed with water. The crude filter cake (46 g) was recrystallized from toluene (160 ml) and n-heptane (60 ml) to afford [(R)-8-fluoro-6-(3-fluoro-phenylsulfanyl)-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl]-urea (37.27 g) in 93.8% yield, 99.8% pure by HPLC: MP=130.7-132.4° C.; MS (M+1)=349; H1 NMR (300 MHz): δ (DMSO): 1.49-1.99 (4H, m), 2.57-2.83 (2H, dt/m), 3.99-3.27 (3H, m), 5.43 (2H, bs, NH), 6.20 (1H, bt, J=6.03), 6.96-7.04 (2H, m), 7.1-7.17 (3H, m), 7.37-7.47 (1H, m); [α]D=24.2° (MeOH).

Workup

  1. customto decline to room temperature
  2. customThe resulting solids were collected
  3. washwashed with water
  4. filtrationThe crude filter cake (46 g)
  5. customwas recrystallized from toluene (160 ml) and n-heptane (60 ml)

Sources & evidence

ORD record
ord-2e4c72caaf104df2b91eb5b2242dd5a4
Source dataset
uspto-grants-2016_06
Patent number
US09365494B2

Reaction notes

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