Hydrochloric Acid → N-(3-chloro-4-fluorophenyl)-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2'-[1,3]dioxolan]-4-amine

HRID 222011Notes

Reaction equation

HRID 222011 reaction equation
Cl[C:2]1[C:3]2[C:10]3[CH2:11][CH2:12][C:13]4([CH2:18][C:9]=3[S:8][C:4]=2[N:5]=[CH:6][N:7]=1)[O:17][CH2:16][CH2:15][O:14]4.[F:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][C:21]=1[Cl:27].Cl>C(O)C>[Cl:27][C:21]1[CH:22]=[C:23]([NH:24][C:2]2[C:3]3[C:10]4[CH2:11][CH2:12][C:13]5([CH2:18][C:9]=4[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[O:17][CH2:16][CH2:15][O:14]5)[CH:25]=[CH:26][C:20]=1[F:19]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 97083-Chloro-4-fluoroanilineHCID 179901054-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2'-[1,3]dioxolane]

Product 1

HCID 17990145N-(3-chloro-4-fluorophenyl)-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2'-[1,3]dioxolan]-4-amineYield 57%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirring solution of 4-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2′-[1,3]dioxolane] (7.0 g, 24.8 mmol) in ethanol (100 mL) was added 4-fluoro-3-chloroaniline (3.6 g, 24.8 mmol) and HCl (4N in dioxane, 0.05 mL). The contents were heated to reflux for 5 h, after which time the contents were removed from heating and allowed to cool to rt. The solvent was removed under reduced pressure, the crude residue suspended in aq NaHCO3 (100 mL), and stirred for 15 min. The contents were again filtered, and the solid filter cake washed with water. The collected yellow solid was triturated with diethyl ether (50 mL) to afford the final product (5.5 g, 57%) as a light yellow solid. 1H-NMR (DMSO-d6) δ 8.41 (s, 1H), 8.28 (s, 1H), 7.78 (dd, 1H), 7.58 (m, 1H), 7.35 (t, 1H), 3.97 (s, 4H), 3.22 (t, 2H), 3.00 (s, 2H), 1.93 (t, 2H); LCMS RT=3.26 min; [M+H]+=392.3.

Workup

  1. temperatureThe contents were heated
  2. temperatureto reflux for 5 h
  3. customafter which time the contents were removed
  4. temperaturefrom heating
  5. customThe solvent was removed under reduced pressure
  6. filtrationThe contents were again filtered
  7. filtrationthe solid filter cake
  8. washwashed with water
  9. customThe collected yellow solid was triturated with diethyl ether (50 mL)

Sources & evidence

ORD record
ord-fd09f64d2a534c7db7696116184cc4ad
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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