Cesium carbonate → 6-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethylamino)phenyl)pyrido[3,2-d]pyrimidin-4-amine

HRID 1049917Notes

Reaction equation

HRID 1049917 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1)[NH:5][CH2:6][CH2:7][N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1.Cl[C:26]1[CH:27]=[CH:28][C:29]2[N:30]=[CH:31][N:32]=[C:33]([NH2:36])[C:34]=2[N:35]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:15]=[C:14]([C:26]2[CH:27]=[CH:28][C:29]3[N:30]=[CH:31][N:32]=[C:33]([NH2:36])[C:34]=3[N:35]=2)[CH:13]=[C:4]([NH:5][CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][CH2:12]2)[CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 867038966-Chloropyrido[3,2-d]pyrimidin-4-amineHCID 900546883-Fluoro-N-(2-(pyrrolidin-1-yl)ethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 727037246-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethylamino)phenyl)pyrido[3,2-d]pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A suspension of crude 31-B (300 mg, 1.0 mmol), 3-A (150 mg, 0.80 mmol), Pd(PPh3)4 (30 mg) and Cs2CO3 (600 mg, 1.8 mmol) in dioxane/H2O (10 mL/1.0 mL) was stirred at 90° C. for 2 h. The reaction solution was partitioned between EtOAc (100 mL) and brine (35 mL). The combined organic layer was washed with water (3×30 mL), concentrated and purified by prep-HPLC (25 mg, 8.9%). LCMS (0-60AB), RT=0.904 min, M+H 352.9 1H-NMR (Methanol-d4, 400 MHz): δ 8.53 (s, 1H), 8.35 (s, 1H), 8.23 (d, J=8.8 Hz, 1H), 8.03 (d, J=8.8 Hz, 1H)), 7.33 (s, 1H), 7.24 (d, J=10.4 Hz, 1H), 6.49 (d, J=11.2 Hz, 1H), 3.60-3.57 (m, 2H), 3.37-3.28 (m, 6H), 2.07-2.04 (m, 2H).

Workup

  1. customThe reaction solution was partitioned between EtOAc (100 mL) and brine (35 mL)
  2. washThe combined organic layer was washed with water (3×30 mL)
  3. concentrationconcentrated
  4. custompurified by prep-HPLC (25 mg, 8.9%)

Sources & evidence

ORD record
ord-de5c8ce5fd5a4e2baeda6af2860d7ec0
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

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