Triethylamine → HCID 86663704, compound

HRID 2044077Notes

Reaction equation

HRID 2044077 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:20][CH:19]=3)[C:11]([C:12]([NH2:14])=[O:13])=[C:10]([O:32][CH2:33][CH2:34][CH3:35])[N:9]=2)[CH2:3]1.[CH3:36][C:37]1[S:41][C:40]([NH:42][C:43](=O)[O:44]C2C=CC=CC=2)=[N:39][CH:38]=1.CCN(CC)CC>C1COCC1.C(Cl)Cl.CO>[CH3:36][C:37]1[S:41][C:40]([NH:42][C:43](=[O:44])[NH:1][C@@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]3[CH:16]=[C:15]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)=[O:25])=[CH:20][CH:19]=4)[C:11]([C:12]([NH2:14])=[O:13])=[C:10]([O:32][CH2:33][CH2:34][CH3:35])[N:9]=3)[CH2:3]2)=[N:39][CH:38]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 57469779HCID 57469779, compoundHCID 66832598HCID 66832598, compound

Product 1

HCID 86663704HCID 86663704, compoundYield 61.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (R)-6-(3-aminopiperidin-1-yl)-4-(4-(morpholine-4-carbonyl)phenylamino)-2-propoxynicotinamide (50 mg, 0.104 mmol), phenyl 5-methylthiazol-2-ylcarbamate (29.1 mg, 0.124 mmol), and Et3N (0.014 mL, 0.104 mmol) in THF (3 mL) in a scintillation vial was stirred at 60° C. for 2 hrs, during which time a white precipitate forms. Left standing overnight at rt. The solid were dissolved in a mixture of CH2Cl2 and MeOH and crude mixture was chromatographed (loaded onto an ISCO Companion 40 g silica gel column and eluted with (90:9:1 CH2Cl2:MeOH: NH4OH)/CH2Cl2 gradient (20-100%) to give 40 mg (R)-6-(3-(3-(5-methylthiazol-2-yl)ureido)piperidin-1-yl)-4-(4-(morpholine-4-carbonyl)phenylamino)-2-propoxynicotinamide as a white solid. LCMS: (M+H)+=623.37. 1H NMR (400 MHz, CDCl3) δ ppm 11.51 (1H, s), 7.93 (1H, br. s.), 7.38 (2H, d, J=8.57 Hz), 7.24 (2H, d, J=8.57 Hz), 6.80 (1H, s), 6.03 (1H, s), 5.94 (1H, br. s.), 4.23-4.37 (2H, m), 3.85-4.05 (2H, m), 3.55-3.82 (8H, m), 3.25-3.53 (4H, m), 2.32 (3H, s), 1.65-1.90 (5 H, m), 0.97 (3H, t, J=7.47 Hz).

Workup

  1. waitLeft
  2. waitstanding overnight at rt
  3. customwas chromatographed (
  4. washeluted with (90:9:1 CH2Cl2:MeOH: NH4OH)/CH2Cl2 gradient (20-100%)

Sources & evidence

ORD record
ord-fb1dbe746fa944bdab1dfec7d830f1b1
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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