Acetic Acid → HCID 178480944, compound

HRID 51612Notes

Reaction equation

HRID 51612 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:25]3[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Na].C(=O)(O)[O-].[Na+]>ClC(Cl)C.O>[CH2:18]([O:17][C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:3]3[C:2]([NH2:1])=[N:7][CH:6]=[N:5][C:4]=3[N:8]([C@H:25]3[CH2:26][CH2:27][C@@H:28]([N:36]4[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]4)[CH2:29][CH2:30]3)[CH:9]=2)=[CH:16][CH:15]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

9

Reactant 6

HCID 176Acetic Acid2×HCID 531671-Methylpiperazine2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 5360545SodiumHCID 22736207HCID 22736207, compound

Product 1

HCID 178480944HCID 178480944, compoundYield 56.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A suspension of the 4-{4-amino-5-[4-(benzyloxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-1-cyclohexanone (1.22 g, 2.96 mmol) in dichloroethane (40 ml) was treated with N-methylpiperazine (0.889 g, 8.88 mmol) and glacial acetic acid (0.534 g, 8.88 mmol) at 0° C. for 1 hour. Subsequently, sodium triacetoxyborohydride (0.816 g, 3.85 mmol) was added and the reaction mixture was stirred overnight. Additional N-methylpiperazine (0.445 g, 4.44 mmol), sodium triaceoxyborohydride (0.407 g, 1.92 mmol), and glacial acetic acid (0.267 g, 4.44 mmol) were added and the reaction mixture was stirred for an additional 1.5 hour. To the reaction solution, a solution of sodium bicarbonate (1.49 g, 17.76 mmol) in 25 mL water was added and stirred for 1 hour. The aqueous layer was extracted with ethyl acetate (4×125 mL), The organic layers were combined, washed with water and brine (each 4×125 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 1.6 g of crude material. The compound was purified by flash chromatography on silica gel using 10% methanol in dichloromethane, 20% methanol in dichloromethane, and then 30% methanol in dichloromethane. The column yielded 0.83 g (56%) of Cis-5-[4-(benzyloxy)phenyl]-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine, and 0.305 g (21%) of transs-5-[4-(benzyloxy)phenyl]-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine.

Workup

  1. stirringthe reaction mixture was stirred for an additional 1.5 hour
  2. stirringstirred for 1 hour
  3. extractionThe aqueous layer was extracted with ethyl acetate (4×125 mL)
  4. washwashed with water and brine (each 4×125 ml),
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give 1.6 g of crude material
  9. customThe compound was purified by flash chromatography on silica gel using 10% methanol in dichloromethane, 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-6a0ddc1f4f514d71b49f95b694d2de94
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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