Tetrahydrofuran → HCID 57794642, compound

HRID 2099766Notes

Reaction equation

HRID 2099766 reaction equation
[OH:1][CH:2]([C:22]1[CH:23]=[C:24]([CH:29]=[CH:30][N:31]=1)[C:25](OC)=[O:26])[CH2:3][C:4]1[CH:12]=[C:11]([CH3:13])[C:10]2[C:6](=[CH:7][N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:9]=2)[CH:5]=1.[O:32]=[C:33]1[N:42]([CH:43]2[CH2:48][CH2:47][N:46]([C:49](OC3C=CC([N+]([O-])=O)=CC=3)=[O:50])[CH2:45][CH2:44]2)[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34]1.[H-].[Na+].[O:63]1CCCC1>>[CH3:13][C:11]1[C:10]2[C:6](=[CH:7][N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:19])([CH3:21])[CH3:20])[N:9]=2)[CH:5]=[C:4]([CH2:3][CH:2]([C:22]2[CH:23]=[C:24]([CH:29]=[CH:30][N:31]=2)[C:25]([OH:26])=[O:63])[O:1][C:49]([N:46]2[CH2:45][CH2:44][CH:43]([N:42]3[CH2:41][C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[NH:34][C:33]3=[O:32])[CH2:48][CH2:47]2)=[O:50])[CH:12]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 57794631HCID 57794631, compoundHCID 57794669HCID 57794669, compound

Product 1

HCID 57794642HCID 57794642, compoundYield 62.8%

Procedure

To a suspension of (±)-methyl 2-(1-hydroxy-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)isonicotinate (233 mg, 0.527 mmol 1.0 equiv) and 4-nitrophenyl 4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate (251 mg, 0.632 mmol, 1.2 equiv) in tetrahydrofuran (6 mL) was added sodium hydride (91 mg, 7 equiv) in one portion. The resulting mixture was stirred at room temperature under nitrogen overnight. The mixture was partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was acidified to pH 5 with acetic acid. The aqueous portion was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by flash column chromatography (20% methanol in methylene chloride) to afford the desired acid (227 mg, 62.8%) as a tan solid. (ESI) 685 (MH)+. HPLC tR=2.19 min.

Workup

  1. customThe mixture was partitioned between water and ethyl acetate
  2. customThe layers were separated
  3. extractionThe aqueous portion was extracted twice with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (20% methanol in methylene chloride)

Sources & evidence

ORD record
ord-8886481e63e6414aa60fd8f8d6883e5e
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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