Water → HCID 136247227, compound

HRID 1022461Notes

Reaction equation

HRID 1022461 reaction equation
Cl[C:2]1[NH:3][C:4](=[O:14])[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][OH:13])[C:6]=2[N:7]=1.[F:15][C:16]1[CH:21]=[C:20]([O:22][CH2:23][CH2:24][O:25][CH3:26])[CH:19]=[C:18]([F:27])[C:17]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.CCN(C(C)C)C(C)C.O>C(O)C.CC#N>[F:27][C:18]1[CH:19]=[C:20]([O:22][CH2:23][CH2:24][O:25][CH3:26])[CH:21]=[C:16]([F:15])[C:17]=1[N:28]1[CH2:29][CH2:30][N:31]([C:2]2[NH:3][C:4](=[O:14])[C:5]3[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][OH:13])[C:6]=3[N:7]=2)[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 21363764HCID 21363764, compoundHCID 136344417HCID 136344417, compound

Product 1

HCID 136247227HCID 136247227, compoundYield 31.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent3×

Procedure

A solution of 2-chloro-7-(2-hydroxyethyl)-3H,4H,7H-pyrrolo[2,3-d]pyrimidin-4-one (150 mg, 0.70 mmol, 1.00 equiv), 1-[2,6-difluoro-4-(2-methoxyethoxy)phenyl]piperazine (192 mg, 0.71 mmol, 1.00 equiv) and DIEA (182 mg, 1.41 mmol, 2.00 equiv) in ethanol (2 mL) was placed in an 8-mL sealed tube. The reaction mixture was irradiated with microwave radiation for 30 min at 140° C. and then cooled back to room temperature. The crude product was collected by filtration then purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column: XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase: water with 10 mmol NH4HCO3 and MeCN (MeCN 35.0%, MeCN up to 50.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 35.0% in 2 min); Detector, UV 254/220 nm to yield 98.3 mg (31%) of 2-[4-[2,6-difluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]-7-(2-hydroxyethyl)-3H,4H,7H-pyrrolo[2,3-d]pyrimidin-4-one as a white solid. 1HNMR (400 MHz, DMSO-d6) δ□ ppm 3.09-3.06 (m, 4H), 3.28 (s, 3H), 3.69-3.61 (m, 8H), 4.02-3.99 (m, 2H), 4.08-4.06 (m, 2H), 4.85 (t, J=5.6 Hz, 1H), 6.23 (d, J=3.2 Hz, 1H), 6.72 (d, J=11.2 Hz, 2H), 6.81 (d, J=3.2 Hz, 1H), 10.81 (s, 1H). LC-MS calcd. for C21H26F2N5O4 [(M+H)+] 450, obsd. 450.3.

Workup

  1. customsealed tube
  2. customThe reaction mixture was irradiated with microwave radiation for 30 min at 140° C.
  3. filtrationThe crude product was collected by filtration
  4. customthen purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  5. customin 1 min
  6. waitdown to 35.0% in 2 min)

Sources & evidence

ORD record
ord-d4dc8aa055bb4c51925b44bd360a88b3
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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