Acetic Acid → HCID 178487630, compound

HRID 51603Notes

Reaction equation

HRID 51603 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([O:18][CH3:19])[CH:12]=3)=[CH:9][N:8]([CH:20]3[CH2:25][CH2:24]C(=O)[CH2:22][CH2:21]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:27](O)(=O)C.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[NH2:17][C:14]1[CH:15]=[CH:16][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:20]3[CH2:25][CH2:24][C@@H:31]([N:32]4[CH2:37][CH2:36][N:35]([CH3:27])[CH2:34][CH2:33]4)[CH2:22][CH2:21]3)[CH:9]=2)=[CH:12][C:13]=1[O:18][CH3:19]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 227363904-[4-amino-5-(4-amino-3-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclohexanone

Product 1

HCID 178487630HCID 178487630, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

4-[4-amino-5-(4-amino-3-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclohexanone (2.25 g, 6.5 mmol), acetic acid (1.17 g, 19.5 mmol) and N-methylpiperazine (1.95 g, 19.5 mmol) were dissolved in dichloroethane (200 ml). Sodium triacetoxyborohydride (2.07 g, 9.75 mmol) was added portionwise and the mixture stirred at room temperature overnight. Saturated sodium bicarbonate solution (150 ml) was added and the aqueous layer extracted with dichloromethane (3×100 ml). The combined organics were washed with water, dried (sodium sulphate), filtered and evaporated to leave a semi-solid whaich was purified by flash silica gel column chromatography using CH2Cl2/methanol (0% MeOH to 50% MeOH in 5% increments). The fractions corresponding to the faster running material were combined and evaporated to give cis-5-(4-amino-3-methoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1.2 g, 43%) as a cream solid. 1H NMR (d6-DMSO): δ 8.1(1H, s), 7.11(1H, s), 6.87(1H, s), 6.79(1H, d), 6.05(2H, bs), 4.80(2H, bs), 4.64(1H, m), 4.08(1H, m), 3.82(3H, s), 3.17(2H, m), 2.37(6H, m), 2.21(3H, s), 2.08(4H, m), 1.70(2H, m), 1.53(2H, m). HPLC (rt=11.24 min, 97.6%).

Workup

  1. extractionthe aqueous layer extracted with dichloromethane (3×100 ml)
  2. washThe combined organics were washed with water
  3. dry with materialdried (sodium sulphate)
  4. filtrationfiltered
  5. customevaporated
  6. customto leave a semi-solid
  7. customwas purified by flash silica gel column chromatography
  8. customevaporated

Sources & evidence

ORD record
ord-73fa0dfe32a24cfea17121ef63e4af96
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

Loading…