Formaldehyde → HCID 71209245, compound

HRID 1485241Notes

Reaction equation

HRID 1485241 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][C:7]([NH:11][C:12]3[N:17]=[C:16]([CH2:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[CH2:26][C:27]([NH2:29])=[O:28])[C:15]([C:30]([F:33])([F:32])[F:31])=[CH:14][N:13]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.C=O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:36][N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[C:7]([NH:11][C:12]3[N:17]=[C:16]([CH2:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[CH2:26][C:27]([NH2:29])=[O:28])[C:15]([C:30]([F:32])([F:33])[F:31])=[CH:14][N:13]=3)[CH:6]=2)[CH2:1]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 60149002HCID 60149002, compound

Product 1

HCID 71209245HCID 71209245, compoundYield 88.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-(2-(2-(2-((1,2,3,4-tetrahydroisoquinolin-6-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (21) (25 mg, 0.055 mmol) was suspended in methanol (2 mL) and 37% aqueous formaldehyde (0.016 mL, 0.22 mmol) was added. The mixture was stirred for five minutes then sodium tri(acetoxy)borohydride (58 mg, 0.27 mmol) was added. After stirring for 2 hours at room temperature the mixture was concentrated and the residue treated with 10% aqueous NaOH (1 mL) for five minutes. Brine (2 mL) was added, and the mixture was extracted with ethyl acetate (5×5 mL). The combined ethyl acetate extracts were washed with brine, dried (sodium sulphate) and evaporated to give the title compound (28) (22.8 mg, 88% yield) as an off-white solid; 1H NMR (400 MHz, d4-MeOD) δ 8.54 (d, J=0.5 Hz, 1H), 7.52 (d, J=1.9 Hz, 1H), 7.47 (dd, J=8.3, 2.2 Hz, 1H), 7.28-7.16 (m, 4H), 7.04 (d, J=8.3 Hz, 1H), 3.66 (s, 2H), 3.60 (s, 2H), 3.21-3.11 (m, 2H), 3.11-3.02 (m, 2H), 2.96 (t, J=6.0 Hz, 2H), 2.76 (t, J=6.1 Hz, 2H), 2.46 (s, 3H). LCMS Method C: rt 4.78 min; m/z 470.1 [M+H]+; m/z 468.1 [M−H]−.

Workup

  1. stirringAfter stirring for 2 hours at room temperature the mixture
  2. concentrationwas concentrated
  3. additionthe residue treated with 10% aqueous NaOH (1 mL) for five minutes
  4. additionBrine (2 mL) was added
  5. extractionthe mixture was extracted with ethyl acetate (5×5 mL)
  6. washThe combined ethyl acetate extracts were washed with brine
  7. dry with materialdried (sodium sulphate)
  8. customevaporated

Sources & evidence

ORD record
ord-8af1ccba1b094680be7e0addf27fc237
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

Loading…