Dichloromethane → (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-(pyrrolidin-1-yl)but-2-en-1-yloxy)quinazoline hydrochloride

HRID 1838550Notes

Reaction equation

HRID 1838550 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[N:13]1([CH2:18]/[CH:19]=[CH:20]/[CH2:21][OH:22])[CH2:17][CH2:16][CH2:15][CH2:14]1.[Cl:23][N:24]([C:32]1[C:41]2[C:36](=[CH:37][C:38](O)=[C:39]([O:42][CH3:43])[CH:40]=2)[N:35]=[CH:34][N:33]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[F:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)[Cl:65]>>[ClH:23].[Cl:65][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:32]2[C:41]3[C:36](=[CH:37][C:38]([O:22][CH2:21]/[CH:20]=[CH:19]/[CH2:18][N:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)=[C:39]([O:42][CH3:43])[CH:40]=3)[N:35]=[CH:34][N:33]=2)=[C:26]([F:31])[CH:27]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22030876(E)-4-(pyrrolidin-1-yl)but-2-en-1-olHCID 1359906824-(Chloro-2-fluoroanilino)7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22478297(E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-(pyrrolidin-1-yl)but-2-en-1-yloxy)quinazoline hydrochlorideYield 33%

Procedure

Diethyl azodicarboxylate (5.91 ml, 37 mmol) was added dropwise to a stirred mixture of (E)-4-(pyrrolidin-1-yl)but-2-en-1-ol (3.97 g, 28 mmol), 4-(chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (3.0 g, 9 mmol), (prepared as described for the starting material in Example 2), and triphenylphosphine (9.84 g, 38 mmol) in methylene chloride (300 ml). The reaction mixture was stirred for 18 hours at ambient temperature. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with methylene chloride/methanol (a gradient from 80/20 to 70/30). The purified product was dissolved in methylene chloride/methanol and 1M ethereal hydrogen chloride (25 ml) was added. The precipitated product was collected by filtration, washed with ether and dried to give (E)-4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-(pyrrolidin-1-yl)but-2-en-1-yloxy)quinazoline hydrochloride (1.62 g, 33%).

Workup

  1. custom(prepared
  2. customThe volatiles were removed by evaporation
  3. customthe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (a gradient from 80/20 to 70/30)
  5. dissolutionThe purified product was dissolved in methylene chloride/methanol
  6. addition1M ethereal hydrogen chloride (25 ml) was added
  7. filtrationThe precipitated product was collected by filtration
  8. washwashed with ether
  9. customdried

Sources & evidence

ORD record
ord-e0c378375e734586bfc65d34a3d05ff1
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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