Sodium Carbonate → HCID 66550743, compound

HRID 1410117Notes

Reaction equation

HRID 1410117 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18]3[CH2:22][CH2:21][CH2:20][C@@H:19]3[CH3:23])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[CH3:24][O:25][C:26]1[N:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:24][O:25][C:26]1[N:31]=[CH:30][C:29]([C:2]2[N:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[CH2:22][CH2:21][CH2:20][C@@H:19]4[CH3:23])[CH:13]=3)[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=2)=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86671787HCID 86671787, compound

Product 1

HCID 66550743HCID 66550743, compoundYield 24.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A mixture of (S)-5-chloro-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (200 mg, 0.58 mmol), 6-methoxypyridin-3-ylboronic acid (134 mg, 0.87 mmol), Pd2(dba)3 (34 mg, 0.058 mmol), X-Phos (0.58 mg, 0.12 mmol) and sodium carbonate (185 mg, 1.74 mmol) in 1,4-dioxane:water (5 mL:5 mL) was heated to reflux for 16 hours. Then water was added, mixture extracted with ethyl acetate, organics combined washed with brine dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give (S)-5-(6-methoxypyridin-3-yl)-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (60 mg, 24.8%) as yellow solid. 1H NMR (300 MHz, CD3OD): δ 9.19 (s, 1H), 9.08 (s, 1H), 8.63 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 7.33 (s, 1H), 7.23-7.12 (m, 2H), 6.88 (d, 1H, J=8.7 Hz), 6.42 (d, 1H, J=6.9 Hz), 3.96 (s, 3H), 3.51-3.46 (m, 1H), 3.30-3.24 (m, 2H), 2.17-2.03 (m, 3H), 1.80-1.75 (m, 1H), 1.22 (d, 3H, J=6.3 Hz). LC-MS: 419 [M+H]+, tR=2.04 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=6.299 min.

Workup

  1. temperatureto reflux for 16 hours
  2. extractionmixture extracted with ethyl acetate
  3. washorganics combined washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe crude product was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-a1163103c49d497f8a0d62a48fdebb99
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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