1-Hydroxybenzotriazole → HCID 90015403, compound

HRID 1057048Notes

Reaction equation

HRID 1057048 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]=[CH:3]1.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.Cl.[CH3:33][C@@H:34]1[CH2:38][CH2:37][CH2:36][N:35]1[C:39]1[N:44]=[C:43]([NH:45][C:46]2[CH:51]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:49]=[CH:48][N:47]=2)[CH:42]=[C:41]([CH:56]2[CH2:60][CH2:59][NH:58][CH2:57]2)[CH:40]=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]([N:58]2[CH2:59][CH2:60][CH:56]([C:41]3[CH:42]=[C:43]([NH:45][C:46]4[CH:51]=[C:50]([C:52]([F:53])([F:54])[F:55])[CH:49]=[CH:48][N:47]=4)[N:44]=[C:39]([N:35]4[CH2:36][CH2:37][CH2:38][CH:34]4[CH3:33])[CH:40]=3)[CH2:57]2)=[O:9])[N:4]=[CH:3]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 117953310HCID 117953310, compound

Product 1

HCID 90015403HCID 90015403, compoundYield 15.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-methylimidazole-4-carboxylic acid (39.79 mg, 0.315 mmol, 1.5 equiv.), HOBT (57.42 mg, 0.420 mmol, 2.0 equiv.), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (81.46 mg; 0.420 mmol, 2.0 equiv.) in chloroform (3.0 mL) was added 6-[(2R)-2-methylpyrrolidin-1-yl]-4-pyrrolidin-3-yl-N-[4-(trifluoromethyl)-2-pyridyl]pyridin-2-amine hydrochloride (90 mg, 0.210 mmol) followed by DIPEA (0.148 mL, 0.841 mmol, 4.0 equiv.). The resulting mixture was stirred at rt for 2 h. It was diluted with DCM (10 mL), washed with 10% citric acid and 1 N NaHCO3, dried over Na2SO4, filtered, concentrated in vacuo, and purified by HPLC to afford 16.1 mg (15.3%) of product as yellow solid. 1H NMR (400 MHz, DMSO) δ 9.74 (s, 1H), 8.80 (s, 1H), 8.41 (d, J=5.1 Hz, 1H), 7.68-7.60 (m, 2H), 7.10 (d, J=5.1 Hz, 1H), 6.39 (s, 1H), 5.90 (s, 1H), 4.48-4.09 (m, 3H), 3.94-3.73 (m, 2H), 3.69 (d, J=5.2 Hz, 3H), 3.56-3.43 (m, 2H), 3.25-3.18 (m, 1H), 2.31-2.13 (m, 1H), 2.12-1.86 (m, 4H), 1.73-1.63 (m, 1H), 1.17 (d, J=6.0 Hz, 3H). LC-MS: m/z=500 (M+H+).

Workup

  1. washwashed with 10% citric acid and 1 N NaHCO3
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified by HPLC

Sources & evidence

ORD record
ord-1fb1690bc84b42ff8629e573e6bc8f24
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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