Dimethyl Sulfoxide → 2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}acetaldehyde

HRID 51598Notes

Reaction equation

HRID 51598 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[NH2:11][C:12]1[C:13]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:23][CH:22]=3)=[CH:19][N:18]([CH:34]3[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][OH:42])[CH2:36][CH2:35]3)[C:14]=2[N:15]=[CH:16][N:17]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl>[NH2:11][C:12]1[C:13]2[C:20]([C:21]3[CH:22]=[CH:23][C:24]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:25][CH:26]=3)=[CH:19][N:18]([CH:34]3[CH2:35][CH2:36][CH:37]([CH2:40][CH:41]=[O:42])[CH2:38][CH2:39]3)[C:14]=2[N:15]=[CH:16][N:17]=1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 227362622-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-ethanol

Product 1

HCID 227361722-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}acetaldehydeYield 52.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

Dimethylsulfoxide (0.040 g, 0.51 mmol) was added into a solution of oxalyl chloride (0.033 g, 0.26 mmol) in dichloromethane (3 mL) at −78° C. The mixture was allowed to warm up to −40° C. and stirred for 15 minutes followed by cooling down to −78° C. again. 2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-ethanol (0.10 g, 0.23 mmol) was added followed by triethylamine (0.12 mg, 1.165 mmol). The mixture was allowed to warm up to 0° C. and saturated aqueous sodium bicarbonate solution (10 mL) was added to quench the reaction. The organic layer was separated from the aqueous layer and washed with 10% aqueous sodium hydorgensulfate solution (4 mL), saturated aqueous sodium bicarbonate solution (4 mL) and saturated aqueous sodium chloride (4 mL). The organic layer was dried over magnesium sulfate and the solvent was removed under reduced pressure. 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}acetaldehyde (0.053 g, 0.12 mmol) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 9.81(s, 1H), 8.33(s, 1H), 7.68(m, 1H), 7.43(d, 2H), 7.38(t, 2H), 7.15(t, 1H), 7.07(m, 4H), 5.14 (br, 2H), 4.72(m, 1H), 2.63-1.72(m, 11H); TLC (methanol/dichloromethane=5:95) Rf 0.41. MS: MH+ 427.

Workup

  1. temperatureby cooling down to −78° C. again
  2. temperatureto warm up to 0° C.
  3. customto quench
  4. customthe reaction
  5. customThe organic layer was separated from the aqueous layer
  6. washwashed with 10% aqueous sodium hydorgensulfate solution (4 mL), saturated aqueous sodium bicarbonate solution (4 mL) and saturated aqueous sodium chloride (4 mL)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-5f31a854d16f4008a75eab26fa7c0033
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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