Formaldehyde → HCID 86695157, compound

HRID 1504000Notes

Reaction equation

HRID 1504000 reaction equation
Cl.[CH3:2][O:3][C@H:4]([CH2:27][CH3:28])[CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:24][CH2:23][CH:22]([NH:25][CH3:26])[CH2:21][CH2:20]4)[C:8]=3[C:7]1=2.C=O.[BH3-][C:32]#N.[Na+]>CO>[CH3:2][O:3][C@H:4]([CH2:27][CH3:28])[CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:20][CH2:21][CH:22]([N:25]([CH3:32])[CH3:26])[CH2:23][CH2:24]4)[C:8]=3[C:7]1=2

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86695158HCID 86695158, compound

Product 1

HCID 86695157HCID 86695157, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-[[(3R)-3-[(2R)-2-methoxybutyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]-N-methylcyclohexan-1-amine hydrochloride (120 mg, 0.28 mmol, 1.00 equiv) and HCHO (0.8 mL in methanol (6 mL) was stirred at room temperature. The resulting solution was stirred for 0.5 h at room temperature. Then NaBH3CN (97.02 mg, 1.54 mmol, 5.48 equiv) was added. The resulting solution was allowed to react, with stirring, for an additional 2 h at room temperature. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 3×50 mL of chloroform/iso-propanol (3/1) and the organic layers combined and concentrated under vacuum. The crude product (100 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-016(Waters)): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 50 mL HCOOH and CH3CN (5.0% CH3CN up to 45.0% in 11 min, up to 95.0% in 2 min, down to 5.0% in 2 min); Detector, UV 254/220 nm. This resulted in 34.2 mg (30%) of Compound I-117 as a colorless oil. 1H NMR (CD3OD, 300 MHz): δ 8.47 (1H, s), 5.26-5.27 (1H, m), 3.31-3.35 (1H, m), 3.26-3.30 (4H, m), 3.08-3.11 (1H, m), 2.95-3.00 (1H, m), 2.64 (1H, m), 2.20-2.42 (10H, m), 1.97-2.08 (3H, m), 1.47-1.75 (7H, m), 0.96-1.01 (3H, t). MS: m/z 404 (M+H)+.

Workup

  1. customto react
  2. stirringwith stirring, for an additional 2 h at room temperature
  3. customThe reaction was then quenched by the addition of 10 mL of water
  4. extractionThe resulting solution was extracted with 3×50 mL of chloroform/iso-propanol (3/1)
  5. concentrationconcentrated under vacuum
  6. customThe crude product (100 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-016(Waters))
  7. waitmobile phase: water with 50 mL HCOOH and CH3CN (5.0% CH3CN up to 45.0% in 11 min
  8. waitup to 95.0% in 2 min
  9. waitdown to 5.0% in 2 min)

Sources & evidence

ORD record
ord-cb5f84a3e05e4c128cb5f04f6d8bd175
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

Loading…