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

HRID 1407936Notes

Reaction equation

HRID 1407936 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 C27H21N5O3.1.6HCl: 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-341b8bc2e1074c6296bcae31d6872c21
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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