Formaldehyde → 6-Methyl-2-pyrrolidin-1-yl-4-p-tolyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

HRID 72803Notes

Reaction equation

HRID 72803 reaction equation
[N:1]1([C:6]2[N:7]=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)[C:9]3[CH2:15][NH:14][CH2:13][CH2:12][C:10]=3[N:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:27](C)=O.[Na+]>CO.[OH-].[Na+]>[CH3:27][N:14]1[CH2:13][CH2:12][C:10]2[N:11]=[C:6]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[N:7]=[C:8]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)[C:9]=2[CH2:15]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 462019712-Pyrrolidin-1-yl-4-p-tolyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

Product 1

HCID 462023066-Methyl-2-pyrrolidin-1-yl-4-p-tolyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidineYield 91%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 2-pyrrolidin-1-yl-4-p-tolyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (0.034 g, 0.12 mmol) in MeOH (2 mL) was added formaldehyde (37% in water; 0.10 mL) and NaBH(OAc)3 (0.030 g, 0.14 mmol). After the reaction was judged complete, the mixture was diluted with 1 N NaOH and extracted with CH2Cl2 (3×). The combined organic layers were dried and concentrated. The resulting residue was purified by FCC (2 M NH3 in MeOH/CH2Cl2) to give 0.033 g (91%) of the title compound. HPLC: Rt=8.2 min. MS (ESI): mass calcd. for C19H24N4, 308.4; m/z found, 309.5 [M+H]+. 1H NMR (CDCl3): 7.44 (d, J=8.1, 2H), 7.24 (d, J=7.9, 2H), 3.61-3.58 (m, 4H), 3.42 (5, 2H), 2.92 (dd, J=6.1, 6.0, 2H), 2.74 (dd, J=6.1, 6.0, 2H), 2.40 (5, 3H), 2.39 (5, 3H), 1.97-1.94 (m, 4H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. customThe combined organic layers were dried
  3. concentrationconcentrated
  4. customThe resulting residue was purified by FCC (2 M NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-7efd0ac50093410e8ee267eca1530717
Source dataset
uspto-grants-2014_09
Patent number
US08829011B2

Reaction notes

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