HCID 1537257, compound → HCID 49872723, compound

HRID 1853413Notes

Reaction equation

HRID 1853413 reaction equation
[NH2:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)=[CH:10][S:11][C:5]=2[N:4]=[CH:3]1.[C:19]12([CH2:29][C:30](Cl)=[O:31])[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:27][CH:21]([CH2:22]3)[CH2:20]1)[CH2:26]2>N1C=CC=CC=1>[C:19]12([CH2:29][C:30]([NH:1][N:2]3[C:7](=[O:8])[C:6]4[C:9]([C:12]5[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=5)=[CH:10][S:11][C:5]=4[N:4]=[CH:3]3)=[O:31])[CH2:26][CH:25]3[CH2:24][CH:23]([CH2:22][CH:21]([CH2:27]3)[CH2:20]1)[CH2:28]2

Participants

4

Reactant 2

HCID 1537257HCID 1537257, compoundHCID 27718821-Adamantaneacetyl chloride

Product 1

HCID 49872723HCID 49872723, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

3-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one (100 mg, 0.383 mmol) was stirred in pyridine (3 mL) at 25° C. 1-Adamantaneacetyl chloride (204.1 mg, 0.96 mmol) was slowly added and the reaction mixture was allowed to stir at 25° C. for 2 hours. The reaction mixture was concentrated to dryness. The resulting material was dissolved in DMSO (3 mL), filtered through a glass microfiber frit and purified by preparative HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide), with UV detection at 254 nm]. Fractions containing the desired product were pooled and concentrated under vacuum to afford the title compound as a white solid (68 mg, 41%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.54-1.70 (m, 12H), 1.92 (br s, 3H), 2.07 (s, 2H), 7.19-7.27 (m, 2H), 7.49-7.56 (m, 2H), 7.62 (s, 1H), 10.90 (br s, 1H); MS (DCI/NH3) m/z 438 (M+H)+. Elemental Analysis calculated for C24H24FN3O2S: C, 65.88; H, 5.53; N, 9.60. Found C, 65.64; H, 5.48; N, 9.55.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutionThe resulting material was dissolved in DMSO (3 mL)
  3. filtrationfiltered through a glass microfiber frit
  4. custompurified by preparative HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide), with UV detection at 254 nm]
  5. additionFractions containing the desired product
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b67e1ab415574e01b7d28df15f3cb0f7
Source dataset
uspto-grants-2015_02
Patent number
US08962639B2

Reaction notes

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