Hydrazine hydrate (1:1) → HCID 59352723, compound

HRID 2385555Notes

Reaction equation

HRID 2385555 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:12]4([C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:14]([CH2:21][C:22]5[CH:27]=[CH:26][C:25]([C:28](=O)[CH2:29][C:30]#[N:31])=[CH:24][CH:23]=5)[C:13]4=[O:33])[CH2:11][O:10][C:9]3=[CH:34][C:5]=2[O:4][N:3]=1.O.[NH2:36][NH2:37]>C(O)C>[NH2:31][C:30]1[CH:29]=[C:28]([C:25]2[CH:24]=[CH:23][C:22]([CH2:21][N:14]3[C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:12]4([C:8]5[C:9](=[CH:34][C:5]6[O:4][N:3]=[C:2]([CH3:1])[C:6]=6[CH:7]=5)[O:10][CH2:11]4)[C:13]3=[O:33])=[CH:27][CH:26]=2)[NH:37][N:36]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 59352662HCID 59352662, compound

Product 1

HCID 59352723HCID 59352723, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-(4-((3-methyl-2′-oxo-6H-spiro[benzofuro[5,6-d]isoxazole-5,3′-indoline]-1′-yl)methyl)phenyl)-3-oxopropanenitrile in ethanol (20 mL) was added hydrazine hydrate (0.40 mL, 15 mmol). The solution was heated at reflux for 4 h, allowed to cool to ambient temperature and concentrated in vacuo. The resultant solid was dissolved in anhydrous methanol (10 mL) and a saturated solution of hydrogen chloride in anhydrous methanol (1.5 mL) was added, causing a precipitate to be deposited. The solid was collected by filtration to obtain 1′-[4-(3-amino-1H-pyrazol-5-yl)benzyl]-3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one (0.14 g, 43%) as a pale yellow solid: mp 191-195° C. (methanol); 1H NMR (300 MHz, DMSO-d6) δ 7.82-7.71 (m, 3H), 7.52 (d, J=8.3 Hz, 2H), 7.31-7.18 (m, 2H), 7.10 (d, J=8.6 Hz, 1H), 7.04-6.97 (m, 2H), 6.40 (s, 1H), 5.16 (d, J=16.3 Hz, 1H), 5.05 (d, J=9.7 Hz, 1H), 4.98-4.89 (m, 2H), 2.42 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 176.3, 164.3, 157.8, 155.9, 145.7, 142.7, 138.0, 130.5, 129.7, 128.3, 127.5, 126.6, 124.7, 124.4, 123.8, 117.8, 109.2, 108.5, 108.4, 81.5, 56.1, 43.5, 9.8; MS (ES+) m/z 463.9 (M+1). Anal. Calcd. for C27H21N6O3.1.6HCl: C, 62.15; H, 4.37; N, 13.42. Found: C, 61.97; H, 4.52; N, 13.15.

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 4 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resultant solid was dissolved in anhydrous methanol (10 mL)
  5. additiona saturated solution of hydrogen chloride in anhydrous methanol (1.5 mL) was added
  6. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-567796d0aa3b44c882f475a87f7dc310
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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