Sodium Carbonate → 2-(2-(1-Aminoisoquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol

HRID 1922904Notes

Reaction equation

HRID 1922904 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[S:10][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[CH:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([NH2:39])=[N:31][CH:30]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:39][C:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:29]([C:2]2[N:3]=[C:4]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:5]3[S:10][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[CH:8][C:6]=3[N:7]=2)=[CH:30][N:31]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 461807242-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-olHCID 674926724-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine

Product 1

HCID 596061952-(2-(1-Aminoisoquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-olYield 6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol (63 mg, 0.20 mmol) in acetonitrile (3.6 ml) in a microwave reaction vessel was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine (110 mg, 0.40 mmol), Bis(triphenylphosphine)palladium(II) chloride (7.02 mg, 0.010 mmol) and 1M sodium carbonate in water (0.60 ml). The reaction vessel was sealed and heated in the microwave at 140° C. for 20 minutes. LC-MS of the reaction mixture showed no more starting material. The solvent was evaporated and the resulting oil was purified on silica gel (0 to 20% of 2N NH3 in MeOH/DCM). The resulting oil was further purified by reversed phase HPLC to give 141 as an off-white solid (4.7 mg, 6%) 1H NMR (DMSO d6, 400 MHz) 9.02 (d, 1H, J=8.4 Hz), 8.26 (s, 1H), 8.26 (d, 1H, J=8.4 Hz), 7.67 (t, 1H, J=7.6 Hz), 7.50 (t, 1H, J=7.6)m 7.33 (s, 1H), 7.11 (s, 2H), 5.84 (s, 1H), 3.98-3.94 (m, 4H), 3.81-3.78 (m, 4H), 1.61 (m, 6H). LCMS m/z: 422 (MH+)

Workup

  1. customThe reaction vessel was sealed
  2. customThe solvent was evaporated
  3. customthe resulting oil was purified on silica gel (0 to 20% of 2N NH3 in MeOH/DCM)
  4. customThe resulting oil was further purified by reversed phase HPLC

Sources & evidence

ORD record
ord-9dec35c99fe04dfb9816fc8c99c09f30
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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