HCID 59551680, compound → HCID 58770779, compound

HRID 657272Notes

Reaction equation

HRID 657272 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH:25]4[CH2:28][N:27]([C:29](=[O:31])[CH3:30])[CH2:26]4)=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[N+](C1C=CC(OC(=O)[NH:44][C:45]2[CH:50]=[CH:49][C:48]([N:51]3[CH2:55][CH2:54][CH2:53][CH2:52]3)=[CH:47][CH:46]=2)=CC=1)([O-])=O>>[N:51]1([C:48]2[CH:49]=[CH:50][C:45]([NH:44][C:6]([N:8]3[CH2:9][CH2:10][CH:11]([C:14]4[C:23]5[C:18](=[CH:19][C:20]([O:24][CH:25]6[CH2:26][N:27]([C:29](=[O:31])[CH3:30])[CH2:28]6)=[CH:21][CH:22]=5)[N:17]=[CH:16][N:15]=4)[CH2:12][CH2:13]3)=[O:5])=[CH:46][CH:47]=2)[CH2:52][CH2:53][CH2:54][CH2:55]1

Participants

3

Reactant 2

HCID 59551680HCID 59551680, compoundHCID 68891845HCID 68891845, compound

Product 1

HCID 58770779HCID 58770779, compoundYield 26%

Procedure

The title compound was prepared from 4-[7-(1-Acetyl-azetidin-3-yloxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (44.1 mg, 103 μmol), as synthesized in the previous step, using (4-pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride, prepared in Example 74a, and using essentially the reaction and work-up procedure described in Example 110b. The title compound was purified by silica flash cartridge chromatography (9:1 DCM/acetone/3% DMEA eluent). The combined fractions (10 mL) were washed with 1M NaHCO3 (1×5 mL) to remove a DMEA+ impurity, and were dried (Na2SO4) and concentrated to provide the title compound (13.8 mg, 26%). 1H-NMR (400 MHz, 95:5 CDCl3/CD3OD) δ 9.13 (s, 1H), 8.16 (d, 1H), 7.31 (dd, 1H), 7.17 (m, 2H), 7.03 (d, 1H), 6.54 (m, 2H), 5.16 (m, 1H), 4.67 (ddd, 1H), 4.51 (dd, 1H), 4.32-4.23 (m, 3H), 4.15 (dd, 1H), 3.70 (tt, 1H), 3.26 (m, 4H), 3.11 (tt, 2H), 2.17-1.97 (m, 8H), 1.94 (s, 3H). LC/MS (ESI): calcd mass 514.3, found 515.3 (MH)+.

Workup

  1. customas synthesized in the previous step
  2. customprepared in Example 74a
  3. customthe reaction
  4. customThe title compound was purified by silica flash cartridge chromatography (9:1 DCM/acetone/3% DMEA eluent)
  5. washThe combined fractions (10 mL) were washed with 1M NaHCO3 (1×5 mL)
  6. customto remove a DMEA+ impurity
  7. dry with materialwere dried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0453f28351ab408f9798228839110d6c
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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