Triethylamine → 2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}ethyl methanesulfonate

HRID 51601Notes

Reaction equation

HRID 51601 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[C:8]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)=[CH:14][N:13]([CH:29]3[CH2:34][CH2:33][CH:32]([CH2:35][CH2:36][OH:37])[CH2:31][CH2:30]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C(N(CC)CC)C>ClCCl>[CH3:1][S:2]([O:37][CH2:36][CH2:35][CH:32]1[CH2:31][CH2:30][CH:29]([N:13]2[C:9]3[N:10]=[CH:11][N:12]=[C:7]([NH2:6])[C:8]=3[C:15]([C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:20][CH:21]=3)=[CH:14]2)[CH2:34][CH2:33]1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chloride3×HCID 227362622-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-ethanol

Product 1

HCID 227363462-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}ethyl methanesulfonateYield 80.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Methanesulfonyl chloride (0.036 g, 0.31 mmol) was added into a solution of 2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-ethanol (0.11 g, 0.26 mmol) and triethylamine (2.5 mL) in dichloromethane (2.5 mL) at 0° C. The mixture was allowed to warm up to ambient temperature and stirred overnight. Methanesulfonyl chloride (0.036 g, 0.31 mmol) and dichloromethane (2.5 mL) was added. The mixture was stirred at ambient temperature for 17 hours. Methanesulfonyl chloride (0.036 g, 0.31 mmol) and dichloromethane (2.5 mL) was added. The mixture was stirred at ambient temperature for 4 hours. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel using methanol/dichloromethane (5:95) as a mobile phase to yield 2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}ethyl methanesulfonate (0.10 g, 0.21 mmol) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 8.31(s, 1H), 7.44 (d, 2H), 7.38(t, 2H), 7.15(t, 1H), 7.08 (m, 5H), 5.31(br, 2H), 4.73(m, 1H), 4.32(t, 2H), 3.03(s, 3H), 1.99-1.61(m, 11H); TLC (methanol/dichloromethane=5:95) Rf 0.37; RP-HPLC (Hypersil C18, 5 μm, 100 A, 250×4.6mm; 25%-100% over 10 min then 100%-25% over 2 min acetonitrile-0.05M ammonium acetate, 1 mL/min) Rt 11.45 min; MS: MH+ 507.

Workup

  1. stirringThe mixture was stirred at ambient temperature for 17 hours
  2. stirringThe mixture was stirred at ambient temperature for 4 hours
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-7345937f56bd4cfda60054af377090b6
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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