Diisopropylethylamine → 3-cyano-N-[(2S)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide

HRID 749411Notes

Reaction equation

HRID 749411 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:28][CH2:29][N:30]2[CH2:33][CH:32]([N:34]3[CH2:39][CH2:38]C(F)C[CH2:35]3)[CH2:31]2)[CH2:9][N:10]([CH3:27])[C:11](=[O:26])[C:12]2[CH:17]=[C:16]([C:18](F)(F)F)[CH:15]=[C:14]([C:22](F)(F)F)[CH:13]=2)=[CH:4][CH:3]=1.Cl.Cl.N1[CH2:46][CH:45](N2CCOCC2)[CH2:44]1.CC[N:55](C(C)C)C(C)C.C(O[BH-](O[C:72](=[O:74])C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:22]([C:14]1[CH:13]=[C:12]([C:11]([N:10]([CH2:9][C@H:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:28][CH2:29][N:30]2[CH2:33][CH:32]([N:34]3[CH2:39][CH2:38][O:74][CH2:72][CH2:35]3)[CH2:31]2)[CH3:27])=[O:26])[C:17]2[CH2:44][CH2:45][CH2:46][CH2:18][C:16]=2[CH:15]=1)#[N:55]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 11157448N-{(2S)-2-(4-Fluorophenyl)-4-[3-(4-fluoropiperidin-1-yl)azetidin-1-yl]butyl}-N-methyl-3,5-bis(trifluoromethyl)benzamideHCID 220613264-(Azetidin-3-yl)morpholine dihydrochloride

Product 1

HCID 112029223-cyano-N-[(2S)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Cyano-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide (see Method 19; 2.38 g, 6.3 mmol) and 4-azetidin-3-ylmorpholine dihydrochloride (see WO 00/63168; 1.49 g, 6.9 mmol) were mixed together with CH2Cl2 (120 mL) and DIPEA (1.63 g, 12.6 mmol). The mixture was stirred until all the chemicals were dissolved. Sodium triacetoxyborohydride (1.87 g, 8.8 mmol) was added and the solution was stirred at room temperature overnight. The solvent was removed and the residue was partitioned between ethyl acetate and saturated NaHCO3 (aq). The phases were separated and the aqueous solution was extracted with ethyl acetate. The combined organic solutions were dried over MgSO4 and the solvent was removed by evaporation. The residue was diluted with a small amount of acetonitrile and the solution was kept in a freezer overnight. The crystals were collected by filtration and more material was then obtained from the mother liquor by an additional crystallisation from acetonitrile. There was obtained 1.43 g (45%) in total of the title compound as an off-white solid. 1H NMR (500 MHz, CD3OD): 1.4-4.2 (cm, 31H), 7.0-7.6 (cm, 6H); LCMS: m/z 505 (M+1)+.

Workup

  1. dissolutionwere dissolved
  2. stirringthe solution was stirred at room temperature overnight
  3. customThe solvent was removed
  4. customthe residue was partitioned between ethyl acetate and saturated NaHCO3 (aq)
  5. customThe phases were separated
  6. extractionthe aqueous solution was extracted with ethyl acetate
  7. dry with materialThe combined organic solutions were dried over MgSO4
  8. customthe solvent was removed by evaporation
  9. additionThe residue was diluted with a small amount of acetonitrile
  10. filtrationThe crystals were collected by filtration and more material
  11. customwas then obtained from the mother liquor by an additional crystallisation from acetonitrile

Sources & evidence

ORD record
ord-6d74529e125a4861bef194cde5872dd7
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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