Pyridine → HCID 59161244, compound

HRID 545519Notes

Reaction equation

HRID 545519 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:17]2[CH2:16][CH2:15][CH:14]([NH:18][C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[CH2:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[C:9]([C:24]#[N:25])[CH:10]=2.[CH3:30][S:31](Cl)(=[O:33])=[O:32].N1C=CC=CC=1.CN(C=O)C>ClCCl>[C:24]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]([CH2:4][C:3]1[CH:26]=[CH:27][CH:28]=[CH:29][C:2]=1[NH:1][S:31]([CH3:30])(=[O:33])=[O:32])[C:17]1[CH2:16][CH2:15][CH:14]([NH:18][C:19](=[O:23])[CH:20]([CH3:21])[CH3:22])[CH2:13][C:12]2=1)#[N:25]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 6228DimethylformamideHCID 31297Methanesulfonyl chloride2×HCID 57431649HCID 57431649, compound

Product 1

HCID 59161244HCID 59161244, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Suspend N-[9-(2-amino-benzyl)-6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (Example 109) (116 mg, 0.3 mmol) in anhydrous dichloromethane (3 mL) under nitrogen. Add methanesulfonyl chloride (0.028 mL, 0.36 mmol) and pyridine (0.032 mL, 0.39 mmol), followed by anhydrous DMF (2 mL) to effect solution. Stir 5.5 h at room temperature. Add additional methanesulfonyl chloride (0.010 mL, 0.13 mmol) and pyridine (0.010 mL, 0.12 mmol) and stir 18 h at room temperature. Dilute with dichloromethane and wash with 1N hydrochloric acid. Backwash the aqueous portion with dichloromethane. Combine the organic portions and wash with brine, dry (MgSO4), filter, and concentrate in vacuo to provide 74 mg of a yellow oil. Absorb the oil on silica with THF and a small amount of methanol and purify by flash chromatography. Elute with a step gradient of 10% ethyl acetate/dichloromethane, 25% ethyl acetate/dichloromethane, and 50% ethyl acetate/dichloromethane to obtain 19 mg (14%) of a light yellow solid. MS (ES): m/z 465 (M+1), 463 (M−1); 1H NMR(DMSO-d6): δ 9.43 (s, 1H), 8.02 (s, 1H), 7.88 (d, 1H, J=7.5 Hz), 7.43-7.36 (m, 3H), 7.31 (dt, 1H, J=7.6, 1.0 Hz), 7.12 (dt, 1H, J=7.5, 0.9 Hz), 6.21 (d, 1H, J=7.5 Hz), 5.54 (s, 2H), 4.06 (m, 1H), 3.12 (s, 3H), 3.04 (dd, 1H, J=15.4, 5.3 Hz), 2.70 (m, 2H), 2.59 (dd, 1H, J=15.4, 8.4 Hz), 2.41 (m, 1H), 1.97 (m, 1H), 1.85 (m, 1H), 1.02 (m, 6H).

Workup

  1. stirringstir 18 h at room temperature
  2. washwash with 1N hydrochloric acid
  3. washwash with brine
  4. dry with materialdry (MgSO4)
  5. filtrationfilter
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-46567b8edefc479388732b33f71a7dc2
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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