Sodium Carbonate → Methyl 3-(7-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

HRID 1410051Notes

Reaction equation

HRID 1410051 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][CH:19]3[CH2:23][O:24][CH3:25])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([CH:41]=[CH:42][CH:43]=2)[C:37]([O:39][CH3:40])=[O:38])O1.C([O-])([O-])=O.[Na+].[Na+]>O.O1CCOCC1.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>[CH3:25][O:24][CH2:23][CH:19]1[CH2:20][CH2:21][CH2:22][N:18]1[C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:34]3[CH:35]=[C:36]([CH:41]=[CH:42][CH:43]=3)[C:37]([O:39][CH3:40])=[O:38])[N:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346513-Methoxycarbonylphenylboronic acid pinacol esterHCID 866717845-chloro-N-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379311Methyl 3-(7-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoateYield 59.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Under N2 atmosphere, 5-chloro-N-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (200 mg, 0.53 mmol), methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (153 mg, 0.58 mmol), Pd(PPh3)4 (40 mg, 0.035 mmol) and Na2CO3 (112 mg, 1.06 mmol) in 5 mL of water was added in 30 mL of 1,4-dioxane. The mixture was stirred at reflux for 18 hours. The solvent was removed under reduce pressure and the residue was purified by silica gel chromatography, eluting with petroleum ether and ethyl acetate (3:1) to give methyl 3-(7-(3-(2-(methoxymethyl)pyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (150 mg, 59%) as a yellow sold. 1H NMR (300 MHz, CDCl3): δ 9.13 (s, 1H), 8.82 (s, 1H), 8.68 (d, 1H, J=7.8 Hz), 8.14 (d, 1H, J=7.8 Hz), 8.06 (s, 1H), 7.54 (t, 1H, J=7.8 Hz), 7.35 (s, 1H), 7.28 (t, 1H, J=7.2 Hz), 7.16 (d, 1H, J=7.8 Hz), 6.49 (d, 1H, J=7.5 Hz), 3.96 (brs, 4H), 3.57-3.50 (brs, 2H), 3.32 (s, 3H), 3.25-3.19 (m, 2H), 2.11-2.02 (m, 5H). LC-MS: 476 [M+H]+, tR=1.93 min. HPLC: 98.15% at 214 nm, 97.85% at 254 nm, tR=5.24 min.

Workup

  1. temperatureat reflux for 18 hours
  2. customThe solvent was removed
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with petroleum ether and ethyl acetate (3:1)

Sources & evidence

ORD record
ord-3fe0eece15534df389177af7157547a0
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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