Diisopropylethylamine → HCID 57872113, compound

HRID 1972330Notes

Reaction equation

HRID 1972330 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([N:26]3[CH:30]=[CH:29][CH:28]=[N:27]3)[CH:15]=2)[CH2:10][C@H:9]1[C:31](O)=[O:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:67][C@@H:68]([CH2:77][CH2:78][CH3:79])[C@H:69]([OH:76])[C:70]([NH:72][CH:73]1[CH2:75][CH2:74]1)=[O:71]>C(Cl)Cl.CN(C)C=O>[CH:73]1([NH:72][C:70](=[O:71])[C@@H:69]([OH:76])[C@@H:68]([NH:67][C:31]([C@@H:9]2[CH2:10][C@@H:11]([O:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=4)[N:17]=[C:16]([N:26]4[CH:30]=[CH:29][CH:28]=[N:27]4)[CH:15]=3)[CH2:12][N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:32])[CH2:77][CH2:78][CH3:79])[CH2:74][CH2:75]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 16739337(2S,3S)-3-Amino-N-cyclopropyl-2-hydroxyhexanamideHCID 69016469HCID 69016469, compound

Product 1

HCID 57872113HCID 57872113, compoundYield 78.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-(7-methoxy-2-(1H-pyrazol-1-yl)quinolin-4-yloxy)pyrrolidine-2-carboxylic acid (5.0 g, 11.0 mmol) dissolved in a mixture of methylene chloride (135 mL) and N,N-dimethylformamide (45 mL) was added 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, (4.97 g, 42.6 mmol) and diisopropylethylamine (7.2 mL, 41.11 mmol), followed by the hydrochloride salt of (2S,3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide (2.45 g, 11.0 mmol). The reaction mixture was stirred at room temperature for 2 hours under nitrogen atmosphere. Completion of reaction was monitored by TLC. The reaction mixture was diluted with methylene chloride (200 mL) and washed with 10% hydrochloric acid (100 mL), followed by with 10% sodium bicarbonate solution (100 mL), water (100 mL) and brine (100 mL). The organic layer was dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure to provide 5.4 g (67.6%) of (2S,4R)-tert-butyl 2-((2S,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)-4-(7-methoxy-2-(1H-pyrazol-1-yl)quinolin-4-yloxy)pyrrolidine-1-carboxylate as an off-white solid (HPLC purity: 98.59% by area, HPLC retention time: 14.74 minutes).

Workup

  1. customCompletion of reaction
  2. washwashed with 10% hydrochloric acid (100 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-022dac5166204a39bb9b44932b2d9d60
Source dataset
uspto-grants-2013_04
Patent number
US08431733B2

Reaction notes

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