Formaldehyde → HCID 73055149, compound

HRID 1778978Notes

Reaction equation

HRID 1778978 reaction equation
C=O.[CH3:3][C:4]1[C:5]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:31][C:32]([NH2:34])=[O:33])=[N:6][C:7]([NH:10][C:11]2[CH:12]=[N:13][C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:15][CH:16]=2)=[N:8][CH:9]=1.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:3][C:4]1[C:5]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:31][C:32]([NH2:34])=[O:33])=[N:6][C:7]([NH:10][C:11]2[CH:12]=[N:13][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:35])[CH2:19][CH2:18]3)=[CH:15][CH:16]=2)=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 73054873HCID 73054873, compound

Product 1

HCID 73055149HCID 73055149, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Formaldehyde (37% wt. in H2O; 0.017 mL, 0.22 mmol) was added to a solution of 2-(2-(2-(5-methyl-2-((6-(piperidin-4-yl)pyridin-3-yl)amino)pyrimidin-4-yl)ethyl)phenyl)acetamide (4) (32 mg, 0.07 mmol) in MeOH (4 mL) under an atmosphere of nitrogen. The resulting solution was stirred for 15 minutes at room temperature then sodium triacetoxyborohydride (63 mg, 0.30 mmol) was added in one portion. After stirring at room temperature for 18 hours a further portion of formaldehyde (37 wt. % in H2O; 0.017 mL, 0.22 mmol) was added and after 15 minutes sodium triacetoxyborohydride (63 mg, 0.30 mmol) was added in one portion. The resulting mixture was stirred at room temperature for 20 hours then the volatiles were removed in vacuo and the residue partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL) and dried over Na2SO4. The volatiles were removed under reduced pressure to give the title compound 5 as an off white solid (20 mg, 61%); 1H NMR (400 MHz, d4-MeOH) δ 8.79 (d, J=2.2 Hz, 1H), 8.15 (dd, J=8.6, 2.7 Hz, 1H), 8.12 (d, J=0.6 Hz, 1H), 7.27-7.23 (m, 2H), 7.20-7.15 (m, 3H), 3.64 (s, 2H), 3.16-3.06 (m, 4H), 2.98 (dd, J=9.2, 6.0 Hz, 2H), 2.72 (tt, J=12.0, 3.9 Hz, 1H), 2.40 (s, 3H), 2.32 (td, J=12.0, 2.4 Hz, 2H), 2.11 (s, 3H), 1.97 (d, J=11.9 Hz, 2H), 1.92-1.80 (m, 2H). LCMS-A: rt 4.237 min; m/z 445 [M+H]+.

Workup

  1. additionwas added in one portion
  2. stirringThe resulting mixture was stirred at room temperature for 20 hours
  3. customthe volatiles were removed in vacuo
  4. customthe residue partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  7. washThe combined organic layers were washed with water (25 mL), brine (25 mL)
  8. dry with materialdried over Na2SO4
  9. customThe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-b1e6d378126a4ee0af8b0cf43fdfce7c
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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