Hydrazine hydrate (1:1) → HCID 178511294, compound

HRID 2052985Notes

Reaction equation

HRID 2052985 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:12]=3)=[CH:9][N:8]([C@@H:25]3[CH2:28][C@H:27]([CH2:29][N:30]4C(=O)C5C(=CC=CC=5)C4=O)[CH2:26]3)[C:4]=2[N:5]=[CH:6][N:7]=1.O.NN>C(O)C>[NH2:30][CH2:29][C@@H:27]1[CH2:26][C@H:25]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:12]=3)=[CH:9]2)[CH2:28]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)2×HCID 178508597HCID 178508597, compound

Product 1

HCID 178511294HCID 178511294, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3.84 g (7.25 mmol) of cis-2-{3-[4-amino-5-(3-benzyloxy-phenyl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutylmethyl}-isoindole-1,3-dione in 100 ml of dry ethanol are added dropwise at RT and under argon 3.75 g (3.64 ml; 74.96 mmol) of hydrazine monohydrate. After 2 h most of the starting material is not yet dissolved, and additional 1.6 ml of hydrazine monohydrate are added thereto (total amount: 14.8 equivalents). The reaction is complete after 20 h. The colorless precipitate is filtered off, and washed with ethanol. The filtrate is evaporated to dryness and the crude compound is purified by chromatography on silicagel (dichloromethane:methanol:aqueous concentrated ammonia=90:10:1) to provide cis-7-(3-aminomethyl-cyclobutyl)-5-(3-benzyloxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine. Analytical HPLC: tR=7.47 min (Grad 1); ES-MS: m/eo=400; 1H-NMR (CDCl3): 8.31/s (1H); 7.3-7.5/m (6H); 7.12/s (1H); 7.05-7.08/2 peaks (2H); 6.99/m (1H); 5.17/m (1H); 5.14/s (2H); 5.04/broad s (2H); 2.87/d (2H); 2.75-2.65/m (2H); 2.2-2.1/m (2H); 1.55/broad s (2H).

Workup

  1. dissolutionAfter 2 h most of the starting material is not yet dissolved
  2. filtrationThe colorless precipitate is filtered off
  3. washwashed with ethanol
  4. customThe filtrate is evaporated to dryness
  5. customthe crude compound is purified by chromatography on silicagel (dichloromethane:methanol:aqueous concentrated ammonia=90:10:1)

Sources & evidence

ORD record
ord-2c11fc116023443d9c9c82598d19a6cc
Source dataset
uspto-grants-2008_02
Patent number
US07326699B2

Reaction notes

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