Formic Acid → HCID 25066468, compound

HRID 1711707Notes

Reaction equation

HRID 1711707 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27](=[O:30])[NH:28][CH3:29])[CH:22]=3)=[CH:16][C:15]=2[F:31])=[O:12])[N:7]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[CH2:38][N:37](C(OCC2C=CC=CC=2)=O)[CH2:36][CH2:35]3)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)=O>CO.[Pd]>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27](=[O:30])[NH:28][CH3:29])[CH:22]=3)=[CH:16][C:15]=2[F:31])=[O:12])[N:7]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[CH2:38][NH:37][CH2:36][CH2:35]3)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 284Formic AcidHCID 67253684HCID 67253684, compound

Product 1

HCID 25066468HCID 25066468, compoundYield 57.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of benzyl 6-(3-tert-butyl-5-(3-(2-fluoro-4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)ureido)-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (93 mg, 0.13 mmol) in methanol (3 mL) was treated with 10% Pd/C (50% wet, 74 mg, 0.03 mmol) and formic acid (88%, 0.60 mL, 14 mmol). The resultant reaction mixture was stirred for 90 min and filtered through Celite, washing forward with methanol. The filtrate was concentrated in vacuo and purified on silica gel to provide 1-(3-tert-butyl-1-(1,2,3,4-tetrahydroisoquinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (42 mg, 56% yield). The product was treated with aqueous HCl (0.1 M, 0.75 mL) to provide 1-(3-tert-butyl-1-(1,2,3,4-tetrahydroisoquinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea hydrochloride. 1H NMR (400 MHz, DMSO-d6) δ 9.38 (br s, 2H), 9.10 (d, J=1.8 Hz, 1H), 9.05 (s, 1H), 8.80 (m, 1H), 8.53 (d, J=5.4 Hz, 1H), 8.15 (t, J=9.1 Hz, 1H), 7.46-7.34 (m, 4H), 7.32 (dd, J=11.6, 2.8 Hz, 1H), 7.18 (m, 1H), 7.05 (m, 1H), 6.39 (s, 1H), 4.33 (br s, 2H), 3.40 (2H obscured by H2O), 3.09 (t, J=6.0 Hz, 2H), 2.79 (d, J=5.0 Hz, 3H), 1.28 (s, 9H); MS (ESI) m/z: 558.3 (M+H+).

Workup

  1. customThe resultant reaction mixture
  2. filtrationfiltered through Celite
  3. washwashing forward with methanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified on silica gel

Sources & evidence

ORD record
ord-0b2f36c7e03343ff817d6b8434166652
Source dataset
uspto-grants-2010_09
Patent number
US07790756B2

Reaction notes

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