Ethyl Acetate → HCID 178517963, compound

HRID 1947273Notes

Reaction equation

HRID 1947273 reaction equation
[CH:1]1([NH:7][C:8]2[C:12]3([CH2:17][CH2:16][N:15]([CH2:18][C:19]4[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=4)[CH2:14][CH2:13]3)[N:11]([C:26]3[CH:31]=[CH:30][C:29]([CH:32]=[CH2:33])=[CH:28][CH:27]=3)[C:10](=[O:34])[N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.B1[CH:40]2[CH2:41][CH2:42][CH2:43][CH:36]1CCC2.[CH3:44]COC(C)=O>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([NH:7][C:8]2[C:12]34[CH2:17][CH2:16][N:15]([CH2:14][CH2:13]3)[CH2:18][C:19]3[CH:24]=[CH:23][C:22](=[CH:21][CH:20]=3)[CH2:44][C:42]3[CH:41]=[CH:40][C:33](=[CH:36][CH:43]=3)[CH2:32][C:29]3[CH:30]=[CH:31][C:26](=[CH:27][CH:28]=3)[N:11]4[C:10](=[O:34])[N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 178436512HCID 178436512, compound

Product 1

HCID 178517963HCID 178517963, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a 0° C. degassed THF (10 mL) solution containing 4-(cyclohexylamino)-8-(4-iodobenzyl)-1-(4-vinylphenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one (860 mg, 1.5 mmol, Intermediate III.3.1b.1) was added 9-BBN (0.5 M THF, 6.0 mL, 3.0 mmol) dropwise. The vessel was warmed to rt and then heated at 70° C. for 40 min. Reaction was diluted with 290 mL degassed THF and 70 mL degassed 3.2 N NaOH. To the biphasic mixture Pd(PPh3)4 (346 mg, 0.3 mmol) was added and the reaction heated at 65° C. for 2 h. The mixture was cooled to rt and diluted with EtOAc (200 mL) and water (200 mL). The layers were separated and the aqueous layer extracted twice more with EtOAc. The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated to give 2 g of crude material. Purification via flash silica chromatography using 10% MeOH in CH2Cl2 gave, upon solvent removal and further drying in vacuo, 546 mg of semi-pure material. Further purification via RP-HPLC (95/5 to 5/95 H2O/AcCN+0.1% TFA, YMC C18 column) gave two separable products, the first more polar product (15 mg) identified as the title example III.3.1c.1: 1H NMR (400 MHz, MeOD) δ 6.90 (dd, J=8.0, 2.0 Hz, 4H), 6.73 (dd, J=8.2, 2.0 Hz, 4H), 3.74 (m, 1H) 3.70 (s, 2H), 3.17 (m, 4H), 2.41 (bd, J=11.2 Hz, 2H), 2.07-1.92 (m, 7H), 1.80-1.65 (m, 6H), 1.39-1.30 (m, 4H); HRMS calc for C28H34N4O [M+H]+: 443.2806; measured: 443.2802

Workup

  1. customTo a 0° C. degassed THF (10 mL) solution
  2. temperatureheated at 70° C. for 40 min
  3. customReaction
  4. additionwas diluted with 290 mL
  5. customdegassed THF and 70 mL
  6. customdegassed 3.2 N NaOH
  7. temperaturethe reaction heated at 65° C. for 2 h
  8. temperatureThe mixture was cooled to rt
  9. customThe layers were separated
  10. extractionthe aqueous layer extracted twice more with EtOAc
  11. washwashed with brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-fa10fe66162749599d8f608fbff8061d
Source dataset
uspto-grants-2013_03
Patent number
US08399473B2

Reaction notes

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