Formaldehyde → HCID 89781131, compound

HRID 1503927Notes

Reaction equation

HRID 1503927 reaction equation
N[CH:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[C:20]3[C:19]4[C@@H:18]([CH2:21][CH:22]([OH:24])[CH3:23])[CH2:17][CH2:16][C:15]=4[S:14][C:13]=3[N:12]=[CH:11][N:10]=2)[CH2:4][CH2:3]1.[CH2:25]=[O:26].[BH3-][C:28]#[N:29].[Na+].[CH3:31]O>>[CH:25]([O:24][C@H:22]([CH3:23])[CH2:21][C@H:18]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:8][CH:5]4[CH2:6][CH2:7][CH:2]([N:29]([CH3:28])[CH3:31])[CH2:3][CH2:4]4)[C:20]=3[C:19]1=2)=[O:26].[CH:25]([O:24][C@@H:22]([CH3:23])[CH2:21][C@H:18]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:8][CH:5]4[CH2:6][CH2:7][CH:2]([N:29]([CH3:28])[CH3:31])[CH2:3][CH2:4]4)[C:20]=3[C:19]1=2)=[O:26]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 86695105HCID 86695105, compound

Product 2

HCID 89781131HCID 89781131, compoundHCID 89781294HCID 89781294, compound

Procedure

To a solution of 1-[(3R)-12-[(4-amino cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propan-2-ol (70 mg, crude) in methanol (5 mL) was added HCHO (37%, 0.8 mL) and stirred for 1 h at room temperature. Then NaBH3CN (29.7 mg, 0.47 mmol, 2.35 equiv) was added and the resulting solution was stirred for additional 2 h at ambient temperature and concentrated under vacuum. The crude product (80 mg) was purified by preparative HPLC under the following conditions (SHIMADZU): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 0.05% HCOOH and CH3CN (6.0% CH3CN up to 50.0% in 25 min); UV detection at 254/220 nm. The product containing fractions were collected and evaporated to remove the water and CH3CN to give (2R)-1-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propan-2-ol formate (12.9 mg) as a white solid and (2S)-1-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propan-2-ol formate (5.6 mg) as a grey solid, respectively.

Workup

  1. stirringthe resulting solution was stirred for additional 2 h at ambient temperature
  2. concentrationconcentrated under vacuum
  3. customThe crude product (80 mg) was purified by preparative HPLC under the following conditions (SHIMADZU)
  4. waitmobile phase: water with 0.05% HCOOH and CH3CN (6.0% CH3CN up to 50.0% in 25 min)
  5. additionThe product containing fractions
  6. customwere collected
  7. customevaporated
  8. customto remove the water and CH3CN

Sources & evidence

ORD record
ord-fb53883696cd4ae7800ebca90698b6f5
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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