Dimethylamine → HCID 57681070, compound

HRID 244166Notes

Reaction equation

HRID 244166 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:12]3[CH2:15][C@H:14]([CH2:16]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:28][NH:29][CH3:30].C1COCC1>>[CH3:28][N:29]([CH2:16][CH:14]1[CH2:13][CH:12]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([I:11])=[CH:9]2)[CH2:15]1)[CH3:30]

Participants

4

Reactant 3

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 178427770HCID 178427770, compound

Product 1

HCID 57681070HCID 57681070, compound

Procedure

A mixture of cis-toluene-4-sulfonic acid 3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutylmethyl ester (1.50 g, 3.01 mmol) and a 2M solution of dimethylamine in THF (30 mL, 60 mmol) was heated to 55° C. for 23 h in a glass pressure tube. The solvent was evaporated, water was added, the mixture was extracted with CH2Cl2 (4×40 mL), and the extracts were washed with brine and dried over MgSO4. The crude material was chromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-8)→5% MeOH in CH2Cl2 (9-24)-10% MeOH in CH2Cl2 (25-35)-10% MeOH in CH2Cl2 with 0.07M NH3 (36-48)], fractions containing product were combined and dried in vacuo. One obtained the title compound as brown solid. 1H NMR (CDCl3, 400 MHz): δ=2.01-2.11 (mc, 2H), 2.26 (s, 6H), 2.30-2.43 (mc, 1H), 2.46 (d, J=6.8 Hz, 2H), 2.69-2.77 (m, 2H), 5.05-5.15 (m, 1H), 5.59 (brs, 2H), 7.20 (s, 1H), 8.26 (s, 1H). MS (ES+): m/z 372.1 (20) [MH+]. HPLC: tR=1.3 min (OpenLynx, polar—5 min).

Workup

  1. customThe solvent was evaporated
  2. additionwater was added
  3. extractionthe mixture was extracted with CH2Cl2 (4×40 mL)
  4. washthe extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe crude material was chromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-8)→5% MeOH in CH2Cl2 (9-24)-10% MeOH in CH2Cl2 (25-35)-10% MeOH in CH2Cl2 with 0.07M NH3 (36-48)], fractions
  7. additioncontaining product
  8. customdried in vacuo

Sources & evidence

ORD record
ord-ad70505e7d1f46b38ffd74ac40e8f6ca
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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