Ammonia → HCID 178508628, compound

HRID 422681Notes

Reaction equation

HRID 422681 reaction equation
[NH3:1].Cl[C:3]1[C:4]2[C:11]([I:12])=[CH:10][N:9]([C@@H:13]3[CH2:16][C@H:15]([CH2:17][OH:18])[CH2:14]3)[C:5]=2[N:6]=[CH:7][N:8]=1.C(=O)=O.CC(C)=O>O1CCOCC1.CC(O)C>[NH2:1][C:3]1[C:4]2[C:11]([I:12])=[CH:10][N:9]([C@@H:13]3[CH2:16][C@H:15]([CH2:17][OH:18])[CH2:14]3)[C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 18522661Acetone cardiceHCID 178521037HCID 178521037, compound

Product 1

HCID 178508628HCID 178508628, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Gaseous ammonia (from a lecture bottle) was bubbled into a suspension of cis-[3-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutyl]-methanol (406.8 mg, 1.12 mmol) in dioxane (10 mL) and iPrOH (10 mL) in a Parr bomb, cooled by dry ice/acetone, for 5 min, then the vessel was sealed and heated to 90° C. overnight. LC/MS after 17 h indicated incomplete conversion. More ammonia was bubbled into the mixture, and heating to 90° C. was continued. After 1 d, conversion was complete. The solvents were evaporated, water was added to the residue, and the pale yellow solid was filtered off and dried in vacuo to give the title compound as a pale yellow solid. The compound was used in the next step without further purification. The aqueous filtrate was extracted with CH2Cl2 (3×20 mL), the combined extracts were dried over MgSO4, filtered and concentrated to give a yellow oil that slowly solidified. Purification by HPLC gave analytically pure material. 1H NMR (CDCl3, 400 MHz): δ=2.40-2.57 (m, 4H), 2.57-2.66 (m, 2H), 3.73 (d, J=4.4 Hz, 2H), 5.03 (quint, J=8.4 Hz, 1H), 5.62 (brs, 2H), 7.21 (s, 1H), 8.26 (s, 1H). 13C NMR (DMSO-d6, 100.6 MHz, DEPT135): δ=29.96 (+), 32.70 (2C, −), 44.42 (+), 50.25 (Cquart), 64.16 (−), 102.98 (Cquart), 126.94 (+), 149.41 (Cquart), 151.72 (+), 157.13 (Cquart). MS (ES+): m/z 345.0 (100) [MH+]. HPLC: tR=1.7 min (OpenLynx, polar—5 min). C11H131IN4O.⅔H2O: C: calc. 37.10. found 36.92; H: calc. 4.06. found 3.88; N: calc. 15.73. found 16.07.

Workup

  1. customthe vessel was sealed
  2. customMore ammonia was bubbled into the mixture
  3. temperatureheating to 90° C.
  4. waitAfter 1 d
  5. customThe solvents were evaporated
  6. additionwater was added to the residue
  7. filtrationthe pale yellow solid was filtered off
  8. customdried in vacuo

Sources & evidence

ORD record
ord-a4eb22e3fc95443f973def572f809f70
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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