Potassium Carbonate → HCID 66838496, compound

HRID 244556Notes

Reaction equation

HRID 244556 reaction equation
Cl[CH2:2][CH:3]1[O:8][CH2:7][C@@H:6]2[CH2:9][S:10][CH2:11][N:5]2[CH2:4]1.[F:12][C:13]([F:18])([F:17])[C:14]([OH:16])=[O:15].[Cl:19][C:20]1[CH:21]=[C:22]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][C:34]([OH:40])=[C:35]([O:38][CH3:39])[CH:36]=3)[N:31]=[CH:30][N:29]=2)[CH:23]=[CH:24][C:25]=1[Cl:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C>[F:12][C:13]([F:18])([F:17])[C:14]([OH:16])=[O:15].[Cl:19][C:20]1[CH:21]=[C:22]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][C:34]([O:40][CH2:2][CH:3]4[O:8][CH2:7][C@@H:6]5[CH2:9][S:10][CH2:11][N:5]5[CH2:4]4)=[C:35]([O:38][CH3:39])[CH:36]=3)[N:31]=[CH:30][N:29]=2)[CH:23]=[CH:24][C:25]=1[Cl:26]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 53630940HCID 53630940, compoundHCID 136335147HCID 136335147, compound

Product 1

HCID 66838496HCID 66838496, compoundYield 9.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of (8aR)-6-(chloromethyl)tetrahydro-1H-[1,3]thiazolo[4,3-c][1,4]oxazine (11.6 mg, 0.0599 mmol), 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetate (salt) (30.0 mg, 0.0644 mmol), and potassium carbonate (45.0 mg, 0.326 mmol) in N,N-dimethylacetamide (1.0 mL) was heated in a sealed tube to 150° C. for 12 h. The crude reaction mixture was directly purified via reverse-phase preparative HPLC (acetonitrile/water/0.1% TFA). Lyophillization of the pure fractions yielded 3.5 mg (8.9%) of N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(8aR)-tetrahydro-1H-[1,3]thiazolo[4,3-c][1,4]oxazin-6-ylmethyl]oxy}quinazolin-4-amine trifluoroacetate. 1H NMR (400 MHz, d6-DMSO): 8.80 (s, 1H), 8.11 (s, 1H), 7.99 (s, 1H), 7.74 (s, 2H), 7.29 (s, 1H), 4.29 (d, 2H), 4.11 (m, 2H), 4.00 (s, 3H), 3.96 (m, 1H), 2.99 (m, 2H), 2.56 (t, 1H), 2.367 (m, 1H); MS (EI) for C22H22N4O3SCl2: 492 (MH+).

Workup

  1. customThe crude reaction mixture
  2. customwas directly purified via reverse-phase preparative HPLC (acetonitrile/water/0.1% TFA)

Sources & evidence

ORD record
ord-e48b5ff40d004ad783f1ec817a320afe
Source dataset
uspto-grants-2014_02
Patent number
US08658654B2

Reaction notes

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