Dimethylformamide → HCID 68308651, compound

HRID 922418Notes

Reaction equation

HRID 922418 reaction equation
COCCCO[N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:16]([NH:18][CH:19]3[CH2:21][CH2:20]3)[CH3:17])[CH:14]=2)[C:9]([CH3:22])=[N:8]1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][C@@H:32]([C:36]([OH:38])=O)[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].ON1[C:44]2C=CC=[CH:48][C:43]=2N=N1.Cl.C(N=C=N[CH2:55][CH2:56][CH2:57]N(C)C)C.CN(C)[CH:63]=[O:64]>C(OCC)(=O)C>[CH:19]1([N:18]([C@@H:16]([C:13]2[CH:14]=[C:15]3[C:10]([C:9]([CH3:22])=[N:8][N:7]3[CH2:44][CH2:43][CH2:48][O:64][CH3:63])=[CH:11][CH:12]=2)[CH3:17])[C:36]([C@@H:32]2[O:33][CH2:34][CH2:35][N:30]([C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:29])[CH2:31]2)=[O:38])[CH2:20][CH2:21]1.[CH:19]1([N:18]([C@H:16]([C:13]2[CH:14]=[C:15]3[C:10]([C:9]([CH3:22])=[N:8][N:7]3[CH2:55][CH2:56][CH2:57][O:64][CH3:63])=[CH:11][CH:12]=2)[CH3:17])[C:36]([C@@H:32]2[O:33][CH2:34][CH2:35][N:30]([C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:29])[CH2:31]2)=[O:38])[CH2:20][CH2:21]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6559076(2R)-4-((tert-butoxy)carbonyl)morpholine-2-carboxylic acidHCID 117868296N-{1-[1-(3-methoxypropoxy)-3-methyl-1H-indazol-6-yl]ethyl}-cyclopropanamine

Product 2

HCID 68308651HCID 68308651, compoundHCID 68308653HCID 68308653, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{1-[1-(3-methoxypropoxy)-3-methyl-1H-indazol-6-yl]ethyl}-cyclopropanamine (2.63 g) and (2R)-4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid (2.32 g) in N,N-dimethylformamide (25 mL) were added 1-hydroxybenzotriazole (1.36 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.11 g) under ice-cooling, and then the mixture was stirred at room temperature for 3 hours. To the reaction mixture was added ethyl acetate, and the mixture was washed with saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate/methanol=30/3/1→9/3/1) to give tert-butyl (2R)-2-[(cyclopropyl{(1R)-1-[1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]ethyl}amino) carbonyl]morpholin-4-carboxylate [Ex(162-1)] (1.71 g) and tert-butyl (2R)-2-[(cyclopropyl{(1S)-1-[1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]ethyl}amino) carbonyl]morpholin-4-carboxylate [Ex(162-1)] (468 mg) as a colorless oil.

Workup

  1. temperaturecooling
  2. washthe mixture was washed with saturated saline
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate/methanol=30/3/1→9/3/1)

Sources & evidence

ORD record
ord-1baade1bc44a41068c0f020ebcbee838
Source dataset
uspto-grants-2016_03
Patent number
US09278944B2

Reaction notes

Loading…