Diisopropylethylamine → HCID 118093745, compound

HRID 625694Notes

Reaction equation

HRID 625694 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:35]=[CH:34][C:12]([O:13][C@H:14]2[C:22]3[C:17](=[C:18]([O:24][C:25]4[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=4)[CH:19]=[CH:20][C:21]=3[F:23])[CH2:16][CH2:15]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].Cl.CN.[CH:39]([N:42](CC)C(C)C)(C)C.[B-](F)(F)(F)F.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C>O1CCCC1>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:35]=[CH:34][C:12]([O:13][C@H:14]2[C:22]3[C:17](=[C:18]([O:24][C:25]4[CH:33]=[CH:32][C:28]([C:29](=[O:30])[NH:42][CH3:39])=[CH:27][CH:26]=4)[CH:19]=[CH:20][C:21]=3[F:23])[CH2:16][CH2:15]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochlorideHCID 118093746HCID 118093746, compound2×

Product 1

HCID 118093745HCID 118093745, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-{(R)-1-[4-((1S,2S)-2-Ethoxycarbonyl-cyclopropyl)-phenoxy]-7-fluoro-indan-4-yloxy}-benzoic acid (Intermediate 23, 100 mg, 0.21 mmol), methylamine hydrochloride (16 mg, 0.23 mmol), N,N-diisopropylethylamine (0.11 mL, 0.63 mmol) and 0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU, 74 mg, 0.23 mmol) are combined in dry tetrahydrofuran (7 mL) and stirred overnight. The mixture is concentrated under vacuum, diluted with ethyl acetate, washed with 1 M aqueous HCl solution, saturated sodium bicarbonate solution and water, dried over sodium sulfate, filtered and the solvent removed. The residue is purified by flash chromatography (50% ethyl acetate in cyclohexane) to give the title compound (Yield 98 mg). LC (METHOD 5): tR=1.36 min; Mass spectrum (ES+): m/z=490 [M+H]+.

Workup

  1. concentrationThe mixture is concentrated under vacuum
  2. additiondiluted with ethyl acetate
  3. washwashed with 1 M aqueous HCl solution, saturated sodium bicarbonate solution and water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed
  7. customThe residue is purified by flash chromatography (50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-04e35360685d48bf8beef1b9069f28ad
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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