Methyl chloroformate → HCID 57974279, compound

HRID 1864346Notes

Reaction equation

HRID 1864346 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH2:28][CH2:29][NH:30][CH3:31])[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.CCN(C(C)C)C(C)C.Cl[C:42]([O:44][CH3:45])=[O:43]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH2:28][CH2:29][N:30]([CH3:31])[C:42](=[O:43])[O:44][CH3:45])[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 69065361N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(methylamino)ethoxy]quinazolin-4-amine

Product 1

HCID 57974279HCID 57974279, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(methylamino)ethoxy]quinazolin-4-amine (obtained as described in Example 1, preparation of starting materials, 217 mg) and DIPEA (0.2 ml) were stirred in DCM (20 ml). Methyl chloroformate (0.043 ml) was added slowly and the resulting solution was stirred for 18 hours. The solution was evaporated and the residue purified by chromatography, eluting with increasing concentrations of methanol in ethyl acetate (5-10%). The appropriate fractions were evaporated to give an oil, which was triturated with acetonitrile to give the title compound as a solid (43 mg, 17%); NMR spectrum (DMSO-d6 @ 373K) 2.88 (s, 3H), 3.30 (s, 3H), 3.75-3.85 (t, 2H), 4.35-4.55 (bs, 2H), 5.30 (s, 2H), 7.10-7.30 (m, 2H), 7.30-7.40 (m, 2H), 7.50-7.60 (m, 2H), 7.70-7.78 (t, 1H), 7.80-7.95 (m, 2H), 8.43 (bs, 1H), 8.75-8.80 (d, 1H), 9.60-9.80 (bs, 1H); Mass spectrum MH+ 494.0.

Workup

  1. customThe solution was evaporated
  2. customthe residue purified by chromatography
  3. washeluting
  4. temperaturewith increasing concentrations of methanol in ethyl acetate (5-10%)
  5. customThe appropriate fractions were evaporated
  6. customto give an oil, which
  7. customwas triturated with acetonitrile

Sources & evidence

ORD record
ord-989a052387d642e4b01b67ecb6e5124e
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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