Methylamine → HCID 11548539, compound

HRID 504156Notes

Reaction equation

HRID 504156 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:16][C:17]([C@@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][N:20]2[S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=2)(=[O:27])=[O:26])=[O:18])[C:13](O)=[O:14])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C1C[N:41]([P+](Br)(N2CCCC2)N2CCCC2)[CH2:40]C1.F[P-](F)(F)(F)(F)F.CN.C1COCC1>C(Cl)Cl>[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C@H:12]([NH:16][C:17]([C@@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][N:20]2[S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:35])([F:37])[F:36])[CH:29]=2)(=[O:26])=[O:27])=[O:18])[C:13](=[O:14])[NH:41][CH3:40])=[CH:9][CH:10]=1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 2733179PyBroPHCID 59428652HCID 59428652, compound

Product 1

HCID 11548539HCID 11548539, compoundYield 60.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a room temperature solution of (S)-3-(4-isopropoxy-phenyl)-2-{[(S)-1-(3-trifluoromethyl-benzenesulfonyl)-piperidine-2-carbonyl]-amino}-propionic acid (319 mg, 0.588 mmol) (prepared according to the method described for the preparation of compound 17e), PyBroP (301 mg, 0.645 mmol), and methylene chloride (8 mL) was added methylamine (3.0 mL of a 2M THF solution) in one portion. The reaction mixture was shaken at room temperature in a sealed vessel for 2.5 h. The reaction mixture was then diluted with methylene chloride, washed with 0.5 N HCl and water successively, dried over MgSO4, filtered, and evaporated. The residue was chromatographed on silica gel eluting with ethyl acetate. Homogenous fractions with Rf=0.32 (silica gel, ethyl acetate) material were combined and concentrated to afford 197 mg (60%) of the title compound as a white foam. LC/MS: RT 3.38 min, Area % 100, m/e 556 (M+H). 1H NMR (400 MHz, d6-DMSO) δ8.01 d (J=8 Hz; Tyr NH), 7.99 brd (J=7.5 Hz; H-6 of ArSO2), 7.94 brs (H-2 of ArSO2), 7.84 q (J=4.5 Hz; CONHMe), 7.72 brd (J=8 Hz; H-4 of ArSO2), 7.59 dd (J=8, 7.5 Hz; H-5 of ArSO2), 7.11 m (2H, AA′-part of AA′MM′; H-2/H-6 of C6H4), 6.82 m (2H, MM′-part of AA′MM′; H-3/H-5 of C6H4), 4.56 brd (J=5 Hz; Pip H-2), 4.53 qq (J=6 Hz, 6; OiPr), 4.21 ddd (J=9, 8, 5.5 Hz; Tyr Ha), 3.65 dm (J=12.5; Pip H-6 eq), 3.17 ddd (J=13, 12.5, 3; Pip H-6ax), 2.84 dd (J=13.5, 5.5; Tyr Hb), 2.66 dd (J=13.5, 9; Tyr H′b), 2.53 d (3H, J=4.5; CONHMe), 1.95 brd (J=13.5; Pip H-3 eq), 1.49 dm (J=12.5 Hz; Pip H-Seq), 1.40 m (Pip H-4 eq), 1.36 m (Pip H-3ax), 1.21 d (3H, J=6 Hz; OiPr), 1.19 d (3H, J=6 Hz; OiPr), 1.16 m (Pip H-5ax), 1.06 m (Pip H-4ax).

Workup

  1. washwashed with 0.5 N HCl and water successively
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was chromatographed on silica gel eluting with ethyl acetate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ee13bb68e8894b6f949e7d093c14b664
Source dataset
uspto-grants-2010_08
Patent number
US07777042B2

Reaction notes

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