Diisopropylethylamine → HCID 45254765, compound

HRID 1916819Notes

Reaction equation

HRID 1916819 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH2:8][O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:21]([NH:23][C:24]3[N:28]([C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=4)[N:27]=[C:26]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH:25]=3)=[O:22])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.[CH3:40][O:41][CH2:42][C:43](Cl)=[O:44].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[C:36]([C:26]1[CH:25]=[C:24]([NH:23][C:21](=[O:22])[NH:20][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:10]([O:9][CH2:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:43](=[O:44])[CH2:42][O:41][CH3:40])[N:7]=3)=[CH:11][CH:12]=2)[N:28]([C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)[N:27]=1)([CH3:39])([CH3:38])[CH3:37]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 58416754HCID 58416754, compound2×

Product 1

HCID 45254765HCID 45254765, compoundYield 20.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 1-(4-((2-aminopyrimidin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate H) (52 mg, 0.100 mmol) in DCM (1.0 mL) and DMF (100 μl) was treated with methoxyacetyl chloride (27 μl, 0.299 mmol) followed by DIPEA (52. μl, 0.299 mmol). After stirring overnight at RT, the volatiles were evaporated and the residue suspended in a mixture of MeOH (2.0 mL) and AcOH (2.0 mL). The suspension was subjected to SCX capture and release. Very little material eluted off hence the SCX from the cartridge was removed and extracted with MeOH (50 mL). After evaporation, an off white solid was obtained and this was triturated from MeOH (1.0 mL) and diethyl ether (5.0 mL) to give N-(4-((4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyrimidin-2-yl)-2-methoxy acetamide (Example 23) as a white solid (12 mg, 19% yield): m/z 594 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 2.40 (3H, s), 3.34 (3H, s), 4.24 (2H, s), 5.34 (2H, s), 6.35 (1H, s), 7.02 (1H, d), 7.35 (2H, d), 7.44 (3H, m), 7.60 (3H, m), 7.95 (1H, m), 8.36 (1H, m), 8.59 (1H, br s), 8.68 (1H, d), 8.80 (1H, br s), 10.44 (1H, br s).

Workup

  1. customthe volatiles were evaporated
  2. additionthe residue suspended in a mixture of MeOH (2.0 mL) and AcOH (2.0 mL)
  3. washVery little material eluted off hence the SCX from the cartridge
  4. customwas removed
  5. extractionextracted with MeOH (50 mL)
  6. customAfter evaporation
  7. customan off white solid was obtained
  8. customthis was triturated from MeOH (1.0 mL) and diethyl ether (5.0 mL)

Sources & evidence

ORD record
ord-1e0d78c9f8d84999ba1514325f286cc9
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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