Trifluoroacetic acid → HCID 57838300, compound

HRID 732274Notes

Reaction equation

HRID 732274 reaction equation
C([O:5][CH2:6][C@H:7]1[CH2:11][O:10][C:9](=[N:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][N:17]=[C:16]3[NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][O:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)=[C:26]([Cl:39])[CH:25]=2)[N:8]1[CH3:40])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl.ClCCCl>[Cl:39][C:26]1[CH:25]=[C:24]([NH:23][C:16]2[C:15]3[C:20](=[CH:21][CH:22]=[C:13]([N:12]=[C:9]4[N:8]([CH3:40])[C@@H:7]([CH2:6][OH:5])[CH2:11][O:10]4)[CH:14]=3)[N:19]=[CH:18][N:17]=2)[CH:29]=[CH:28][C:27]=1[CH2:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57931718HCID 57931718, compound2×

Product 1

HCID 57838300HCID 57838300, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-(2-{4-[3-Chloro-4-(3-fluoro-phenoxymethyl)-phenylamino]-quinazolin-6-ylimino}-3-methyl-oxazolidin-4-yl)-methanol is prepared from (S)—N6-(4-tert-butoxymethyl-3-methyl-oxazolidin-2-ylidene)-N4-[3-chloro-4-(3-fluoro-phenoxymethyl)-phenyl]-quinazoline-4,6-diamine. TFA (1 ml) is added to (S)—N6-(4-tert-butoxymethyl-3-methyl-oxazolidin-2-ylidene)-N4-[3-chloro-4-(3-fluoro-phenoxymethyl)-phenyl]-quinazoline-4,6-diamine (0.104 g, 0.184 mmol) in 1 ml methylene chloride at 0° C. After stirring for 2 hours at 0° C. and 3 hours at room temperature, the reaction mixture is diluted with 1,2-dichloroethane and concentrated. The residue is diluted with methylene chloride and washed with 10% Na2CO3. The aqueous layer is extracted with methylene chloride, and the combined organic extracts dried (Na2SO4) and concentrated to give 60 mg (64%) pure desired product. MS ESI (+) m/z 508, 510 (M+1, Cl pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.7 (s, 1H), 8.1 (s, 1H), 7.8-7.4 (m, 6H), 7.2 (m, 1H), 6.8-6.7 (m, 3H), 5.1 (s, 2H), 4.5 (m, 2H), 4.0 (dd, 1H, J=13, 3.9 Hz), 3.9 (m, 1H), 3.8 (br d, 1H, J=13.0 Hz), 3.1 (s, 3H).

Workup

  1. concentrationconcentrated
  2. additionThe residue is diluted with methylene chloride
  3. washwashed with 10% Na2CO3
  4. extractionThe aqueous layer is extracted with methylene chloride
  5. dry with materialthe combined organic extracts dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9a3a1a4d865a4c3e9e1b7be82ec61738
Source dataset
uspto-grants-2009_09
Patent number
US07585975B2

Reaction notes

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