Diisopropylethylamine → 3-Amino-5-[4-tert-butoxycarbonylamino-2-(3,4-dichloro-phenyl)-butyrylamino]-indazole-1-carboxylic acid tert-butyl ester

HRID 1823909Notes

Reaction equation

HRID 1823909 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH2:17])=[CH:14][CH:15]=2)[C:10]([NH2:18])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:43]([O:47][C:48]([NH:50][CH2:51][CH2:52][CH:53]([C:57]1[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=1)[C:54](O)=[O:55])=[O:49])([CH3:46])([CH3:45])[CH3:44].C(N(C(C)C)CC)(C)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:54](=[O:55])[CH:53]([C:57]3[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=3)[CH2:52][CH2:51][NH:50][C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])=[CH:14][CH:15]=2)[C:10]([NH2:18])=[N:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 221479534-tert-Butoxycarbonylamino-2-(3,4-dichlorophenyl)-butyric acidHCID 23571038tert-butyl 3,5-diamino-1H-indazole-1-carboxylate

Product 1

HCID 235710413-Amino-5-[4-tert-butoxycarbonylamino-2-(3,4-dichloro-phenyl)-butyrylamino]-indazole-1-carboxylic acid tert-butyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3,5-diamino-indazole-1-carboxylic acid tert-butylester (2.17 g, 8.75 mmol), PyBroP (4.1 g, 8.75 mmol) and 4-tert-butoxycarbonylamino-2-(3,4-dichloro-phenyl)-butyric acid (3 g, 8.75 mmol) in dichloromethane (100 mL) was added diisopropylethylamine (3.0 mL, 17.5 mmol) at 0° C. The resulting mixture was allowed to warm to room temperature over 4 hours then was concentrated and the residue partitioned between EtOAc and ammonium chloride (saturated, aqueous). The organic phase was separated and washed with sodium bicarbonate (saturated, aqueous), then dried (sodium sulfate) and concentrated to a brown foam. Purification by column chromatography (silica, 20% petroleum ether-EtOAc gave the title compound as a light brown solid (2.92 g, 58%); 1H NMR (400 MHz, DMSO) 1.36 (9H, s), 1.56 (9H, s), 1.80–1.90 (1H, m), 2.10–2.20 (1H, m), 2.89 (2H, m), 6.29 (2H, brs), 6.87 (1H, t), 7.38 (1H, d), 7.45 (1H, d), 7.61–7.65 (2H, m), 7.90 (1H, m), 8.19 (1H, s), 10.30 (1H, s); MS (ES+) m/e=578.

Workup

  1. concentrationthen was concentrated
  2. customthe residue partitioned between EtOAc and ammonium chloride (saturated, aqueous)
  3. customThe organic phase was separated
  4. washwashed with sodium bicarbonate (saturated, aqueous)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated to a brown foam
  7. customPurification by column chromatography (silica, 20% petroleum ether-EtOAc

Sources & evidence

ORD record
ord-7da8f2633a434db3a7fcc1cfc1a04d1b
Source dataset
uspto-grants-2006_05
Patent number
US07041687B2

Reaction notes

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