Piperidin-4-ol → 7-cyclopentyl-2-[5-(4-hydroxy-piperidine-1-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide

HRID 1853232Notes

Reaction equation

HRID 1853232 reaction equation
CO[C:3](=[O:30])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:12]=[CH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:24])[N:21]([CH3:23])[CH3:22])[N:17]([CH:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)[C:15]=3[N:16]=2)=[N:6][CH:5]=1.[NH:31]1[CH2:36][CH2:35][CH:34]([OH:37])[CH2:33][CH2:32]1.C([Mg]Cl)(C)C>C(Cl)Cl>[CH3:23][N:21]([CH3:22])[C:20]([C:18]1[N:17]([CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29]2)[C:15]2[N:16]=[C:11]([NH:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([N:31]4[CH2:36][CH2:35][CH:34]([OH:37])[CH2:33][CH2:32]4)=[O:30])=[CH:5][N:6]=3)[N:12]=[CH:13][C:14]=2[CH:19]=1)=[O:24]

Participants

5

Reactant 3

HCID 79341Piperidin-4-olHCID 67240111methyl 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinateHCID 178418918HCID 178418918, compound2×

Product 1

HCID 583154217-cyclopentyl-2-[5-(4-hydroxy-piperidine-1-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamideYield 51.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(7-cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-nicotinic acid methyl ester (200 mg, 0.49 mmol) and piperidin-4-ol (500 mg, 4.9 mmol) in 5 mL of CH2Cl2 is added dropwise a solution of iPrMgCl (2.45 mL, 4.9 mmol) at 0° C. and allow to warm up to room temperature overnight. After 18 h, added another 10 equivalents of i-PrMgCl and stirred for another 5 h. The reaction mixture is quenched with saturated NH4Cl and extracted with dichloromethane (3×100 mL). The combine organic ished with NaCl and dried over Na2SO4 and concentrated. Following SiO2 chromatography, eluting with 85/15% (CH2Cl2/MeOH) gave 7-cyclopentyl-2-[5-(4-hydroxy-piperidine-1-carbonyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (120 mg, 51%). MS (ESI) in 478.3 (M+H)+

Workup

  1. customThe reaction mixture is quenched with saturated NH4Cl
  2. extractionextracted with dichloromethane (3×100 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. washFollowing SiO2 chromatography, eluting with 85/15% (CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-a275785ad03b4abc8d6de03903ed2348
Source dataset
uspto-grants-2015_02
Patent number
US08962630B2

Reaction notes

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