Diisopropylethylamine → HCID 66833305, compound

HRID 2044081Notes

Reaction equation

HRID 2044081 reaction equation
Cl[C:2]1[CH:10]=[C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[NH:26]1[CH2:31][CH2:30][CH2:29][C@@H:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:27]1.C(N(C(C)C)C(C)C)C>CN1CCCC1=O.C(OCC)(=O)C>[C:6]([C:5]1[C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)=[CH:10][C:2]([N:26]2[CH2:31][CH2:30][CH2:29][C@@H:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[CH2:27]2)=[N:3][CH:4]=1)(=[O:7])[NH2:8]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 57489631HCID 57489631, compound

Product 1

HCID 66833305HCID 66833305, compoundYield 41.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 6-chloro-4-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (230 mg, 0.637 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (166 mg, 0.829 mmol) in N-methyl-2-pyrrolidinone (2 mL) was treated with N-ethyl-N-isopropylpropan-2-amine (107 mg, 0.829 mmol) in a vial, sealed and heated in a heating block at 120° C. for 2 days. The mixture was diluted with ethyl acetate and washed with water. Concentrated and the dark residue was chromatographed (ISCO Companion 12 g silica gel column and eluted with ethyl acetate) to give 140 mg of (R)-tert-butyl 1-(5-carbamoyl-4-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate as a white solid. LCMS: (M+H)+=525.21. 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (s, 9H) 1.50-1.65 (m, 2H) 1.68-1.81 (m, 1H) 1.91 (d, J=10.77 Hz, 1H) 3.16-3.36 (m, 2H) 3.55-3.80 (m, 10H) 3.88 (dd, J=12.85, 3.41 Hz, 1H) 4.68 (d, J=6.81 Hz, 1H) 5.75 (s, 2H) 6.41 (s, 1H) 7.30 (d, J=8.57 Hz, 2H) 7.44 (d, J=8.57 Hz, 2H) 8.32 (s, 1H) 10.33 (s, 1H).

Workup

  1. customsealed
  2. washwashed with water
  3. concentrationConcentrated
  4. customthe dark residue was chromatographed
  5. wash(ISCO Companion 12 g silica gel column and eluted with ethyl acetate)

Sources & evidence

ORD record
ord-b40ec5ce59e54cb08e1bf19b75113c44
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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