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

HRID 2089044

Reaction equation

HRID 2089044 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.[C:34]1(=O)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[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][CH:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)[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

6

Reactant 3

HCID 7967CyclohexanoneHCID 5003444Sodium cyanoborohydrideHCID 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 871916866-chloro-N-(4-{[4-(cyclohexylamino)cyclohexyl]methyl}cyclohexyl)-4-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-amineYield 34.4%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

A suspension of Example 237 (80.0 mg, 0.171 mmol) in MeOH (3 mL) was treated with cyclohexanone (0.035 mL, 0.342 mmol). After 30 minutes, sodium cyanoborohydride (21.5 mg, 0.342 mmol) and zinc chloride (0.699 mg, 5.13 μmol) were added. The reaction was stirred at room temperature overnight. The mixture was concentrated. The residue was treated with sat. NaHCO3 and extracted with EtOAc (2×). The combined organic layers were dried and purified by reverse-phase HPLC as described in Example 56 to give the title compound (32.4 mg) as trifluoroacetic acid salts. 1H NMR (400 MHz, CD3OD) ppm 0.96-1.48 (m, 15H), 1.59-1.96 (m, 10H), 2.01-2.17 (m, 5H), 3.12-3.23 (m, 2H), 3.70 (m, 1H), 3.96 (s, 3H), 6.84-7.01 (m, 2H), 7.93 (m, 1H), 7.99 (s, 1H), 8.10 (s, 1H). MS (DCI+) m/z 550.4 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. additionThe residue was treated with sat. NaHCO3
  3. extractionextracted with EtOAc (2×)
  4. customThe combined organic layers were dried
  5. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-d3fd9965c7a1477885fa3ac2000d29f9
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Linked notes

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