1,2-Dichloroethane → N-[4-[(4-{[6-chloro-4-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]amino}cyclohexyl)methyl]cyclohexyl]cyclopropanecarboxamide

HRID 2089046

Reaction equation

HRID 2089046 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH:9]2[CH2:14][CH2:13][CH:12]([NH:15][C:16]3[CH:21]=[C:20]([C:22]4[C:30]5[C:25](=[N:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=5)[NH:24][CH:23]=4)[CH:19]=[C:18]([Cl:33])[N:17]=3)[CH2:11][CH2:10]2)[CH2:4][CH2:3]1.[CH:34]1([C:37](O)=[O:38])[CH2:36][CH2:35]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)CC)C>CN(C=O)C.O>[Cl:33][C:18]1[N:17]=[C:16]([NH:15][CH:12]2[CH2:11][CH2:10][CH:9]([CH2:8][CH:5]3[CH2:6][CH2:7][CH:2]([NH:1][C:37]([CH:34]4[CH2:36][CH2:35]4)=[O:38])[CH2:3][CH2:4]3)[CH2:14][CH2:13]2)[CH:21]=[C:20]([C:22]2[C:30]3[C:25](=[N:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[NH:24][CH:23]=2)[CH:19]=1

Participants

8

Reactant 5

HCID 111,2-Dichloroethane2×HCID 8471Triethylamine2×HCID 15655Cyclopropanecarboxylic acidHCID 757711-Hydroxybenzotriazole2×HCID 87191065N-{4-[(4-aminocyclohexyl)methyl]cyclohexyl}-6-chloro-4-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-amine

Product 1

HCID 87191602N-[4-[(4-{[6-chloro-4-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]amino}cyclohexyl)methyl]cyclohexyl]cyclopropanecarboxamideYield 37.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of Example 237 (68.5 mg, 0.146 mmol), cyclopropanecarboxylic acid (0.013 mL, 0.161 mmol), HOBT (26.9 mg, 0.176 mmol), EDC (33.7 mg, 0.176 mmol), and triethylamine (0.027 mL, 0.190 mmol) in DMF (2.5 mL) was stirred at room temperature overnight. More EDC (0.6 eq), HOBT (0.6 eq), acid (0.6 eq) and triethylamine (0.7 eq) were added. After 6 hours, water was added to reaction mixture. The precipitate was filtered and purified by reverse-phase HPLC as described in Example 56 to give the title compound (29.0 mg) as trifluoroacetic acid salts. 1H NMR (400 MHz, CD3OD) ppm 0.67-0.76 (m, 2H), 0.77-0.87 (m, 2H), 0.93-1.45 (m, 12H), 1.47-1.96 (m, 10H), 3.57 (m, 1H), 3.71 (m, 1H), 87 (m, 0.6H), 3.96 (s, 3H), 4.02 (m, 0.4H), 6.88-7.07 (m, 2H), 7.94 (m, 1H), 8.04 (s, 1H), 8.11 (s, 1H). MS (DCI+) m/z 536.4 (M+H)+.

Workup

  1. filtrationThe precipitate was filtered
  2. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-df35283ac11f4455b129bd59e1578034
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Linked notes

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