Lithium Chloride → HCID 58949520, compound

HRID 1676338Notes

Reaction equation

HRID 1676338 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:19]2[C:20](=[O:33])[N:21]([CH3:32])[C:22]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:23][CH:24]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH3:34][NH:35][C:36]([C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1)=[O:37].[Li+].[Cl-]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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:3]=[C:4]([C:19]2[C:20](=[O:33])[N:21]([CH3:32])[C:22]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:23][CH:24]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:41]3[CH:42]=[CH:43][C:38]([C:36]([NH:35][CH3:34])=[O:37])=[CH:39][CH:40]=3)[S:17][C:10]=12

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 673484955-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Product 1

HCID 58949520HCID 58949520, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.018 g, 0.032 mmol), 4-(methylcarbamoyl)phenylboronic acid (0.007 g, 0.038 mmol), Pd(PPh3)4 (0.002 g, 0.002 mmol) and LiCl (0.005 g, 0.126 mmol) in dioxane (1 mL) and 2M aqueous Na2CO3 (1 mL) was stirred at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 10:1 CH2Cl2/MeOH. The product was obtained (9.5 mg; 52%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.04 (br s, 1H), 8.60-8.53 (m, 2H), 8.20 (s, 1H), 8.11 (s, 1H), 8.04-7.94 (m, 4H), 7.89 (dd, 1H), 7.69 (m, 1H), 7.57-7.48 (m, 3H), 7.38 (m, 2H), 7.17 (m, 1H), 6.70 (dd, 1H), 3.59 (s, 3H), 2.82 (d, 3H). LRMS (APCI pos) m/e 578 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 10:1 CH2Cl2/MeOH
  10. customThe product was obtained (9.5 mg; 52%) as a pale yellow solid

Sources & evidence

ORD record
ord-b26206ee8d1740829820d195e09429bb
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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