Diisopropylethylamine → 2-(4-bromophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl){2-[(2H-tetrazol-5-ylacetyl)amino]ethyl}amino]-2H-indazole-3-carboxamide

HRID 1037548Notes

Reaction equation

HRID 1037548 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]([S:28]([CH3:31])(=[O:30])=[O:29])[C:5]1[C:6]([CH:25]2[CH2:27][CH2:26]2)=[CH:7][C:8]2[C:12]([CH:13]=1)=[N:11][N:10]([C:14]1[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=1)[C:9]=2[C:21]([NH:23][CH3:24])=[O:22].[NH:32]1[C:36]([CH2:37][C:38](O)=[O:39])=[N:35][N:34]=[N:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[Br:20][C:17]1[CH:16]=[CH:15][C:14]([N:10]2[C:9]([C:21]([NH:23][CH3:24])=[O:22])=[C:8]3[C:12]([CH:13]=[C:5]([N:4]([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:3][CH2:2][NH:1][C:38](=[O:39])[CH2:37][C:36]4[N:32]=[N:33][NH:34][N:35]=4)[C:6]([CH:25]4[CH2:26][CH2:27]4)=[CH:7]3)=[N:11]2)=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 569627726-[(2-aminoethyl)(methylsulfonyl)amino]-2-(4-bromophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamideHCID 178525261HCID 178525261, compound

Product 1

HCID 569628452-(4-bromophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl){2-[(2H-tetrazol-5-ylacetyl)amino]ethyl}amino]-2H-indazole-3-carboxamideYield 41.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of Compound (7) (34 mg, 67 μmol) and tetrazole acetic acid (10 mg, 81 μmol) in DMF (3 mL) at 0° C. was added HATU (31 mg, 81 μmol) and DIPEA (18 μL, 0.1 mmol). The mixture was stirred at RT for 40 min. Ethyl acetate (5 mL) was added and the mixture was washed with 1M hydrochloric acid and saturated sodium bicarbonate. The combined aqueous phase was neutralised to pH 7 (by addition of 6M hydrochloric acid) and lyophilised. The crude material was then purified by reverse phase flash column chromatography eluting with ACN/water (5-100%) to give Compound (8) (17 mg, 41%). ESI-MS m/z calculated for [M+H]+: 616.11/618.11; found: 615.96/617.96. 1H NMR (400 MHz, d4-MeOH) δ 9.42 (s, 1H), 9.27 (d, J=8.7 Hz, 2H), 9.10 (d, J=8.7 Hz, 2H), 8.87 (s, 1H), 5.55-5.37 (m, 2H), 5.37-5.14 (m, 2H), 5.01 (t, J=6.5 Hz, 2H), 4.70 (s, 3H), 4.52 (s, 3H), 3.95-3.73 (m, 1H), 2.69-2.41 (m, 3H), 2.27-2.10 (m, 1H).

Workup

  1. washthe mixture was washed with 1M hydrochloric acid and saturated sodium bicarbonate
  2. additionThe combined aqueous phase was neutralised to pH 7 (by addition of 6M hydrochloric acid)
  3. customThe crude material was then purified by reverse phase flash column chromatography
  4. washeluting with ACN/water (5-100%)

Sources & evidence

ORD record
ord-396c00d7e8394a0b94c7c91b13a3fc7d
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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