Sodium Bicarbonate → HCID 22347421, compound

HRID 1169269Notes

Reaction equation

HRID 1169269 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13](=[O:14])[C:12]2[S:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[CH:18]=O.[N:20]1([CH2:25][C:26]2[CH:27]=[C:28]([CH:30]=[CH:31][CH:32]=2)[NH2:29])[CH2:24][CH2:23][CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13](=[O:14])[C:12]2[S:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[CH2:18][NH:29][C:28]1[CH:30]=[CH:31][CH:32]=[C:26]([CH2:25][N:20]2[CH2:21][CH2:22][CH2:23][CH2:24]2)[CH:27]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 10964073-(Pyrrolidin-1-ylmethyl)anilineHCID 5049666Sodium triacetoxyborohydrideHCID 12088010HCID 12088010, compound

Product 1

HCID 22347421HCID 22347421, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a mixture of 3-(2-chloro-phenyl)-4-oxo-3,4-dihydro-thieno[3,2-d]pyrimidine-2-carbaldehyde (0.326 g, 1.13 mmol) and 3-(pyrrolidin-1-yl-methyl)-aniline (0.132 g, 0.75 mmol) in dichloroethane (10 mL) was added sodium triacetoxyborohydride (0.477 g, 2.25 mmol) portionwise. The reaction was stirred for 24 hours, and then carefully poured into saturated aqueous sodium bicarbonate and repeatedly extracted with chloroform. The combined organic phase was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel (12 g, packed in chloroform). After eluting with chloroform (25 mL), elution was continued with 2-5% methanol/chloroform. Fractions containing the product [silica gel tic R,=0.20 (9:1 chloroform/methanol with 1% triethylamine)] were combined and concentrated to afford 0.166 9 (53%) of the free base of the title product as a viscous oil which had: 1H NMR δ 7.84 (d, J=5.5 Hz, 1H), 7.65 (m, 1H), 7.52 (sym m, 2H), 7.40 (d, J=5 Hz, 1H), 7.37 (m, 1H), 7.07 (t, J=8 Hz, 1H), 6.66 (d, J=7.5 Hz, 1H), 6.61 (s, 1H), 6.37 (dd, J=2, 8 Hz, 1H), 5.02 (br t, J=5 Hz, 1H), 3.94 (dd, J=5, 17 Hz, 1H), 3.84 (dd, J=5, 17 Hz, 1H), 3.51 (s, 2H), 2.48 (br s, 4H), 1.75 (br s, 4H). This oil was taken up in ether and treated with 1 N ethereal hydrochloric acid (0.75 mL, 0.75 mmol). The resulting slurry was concentrated and dried to afford 0.115 g (31%) of 3-(2-chloro-phenyl)-2-[(3-pyrrolidin-1-ylmethyl-phenylamino)-methyl]-3H-thieno[3,2-d]pyrimidin-4-one hydrochloride as a tan solid which had: mp 148-151° C.

Workup

  1. extractionrepeatedly extracted with chloroform
  2. washThe combined organic phase was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customchromatographed on silica gel (12 g, packed in chloroform)
  6. washAfter eluting with chloroform (25 mL), elution
  7. additionFractions containing the product [silica gel tic R,=0.20 (9:1 chloroform/methanol with 1% triethylamine)]
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-35a0e966269449a99e236842c6ded84d
Source dataset
uspto-grants-2003_09
Patent number
US06627755B1

Reaction notes

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