Formaldehyde → HCID 86695152, compound

HRID 1503998Notes

Reaction equation

HRID 1503998 reaction equation
Cl.N[C:3]1([CH2:27][CH3:28])[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][C@H:23]([OH:26])[CH2:24][CH3:25])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1.[CH2:29]=O.[BH3-][C:32]#[N:33].[Na+]>CO>[CH3:29][N:33]([CH3:32])[C:3]1([CH2:27][CH3:28])[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][C@H:23]([OH:26])[CH2:24][CH3:25])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86695153HCID 86695153, compound

Product 1

HCID 86695152HCID 86695152, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (2R)-1-[(3R)-12-[(4-amino-4-ethylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol hydrochloride (90 mg, 0.21 mmol, 1.00 equiv) and HCHO (0.8 mL)(37%) in methanol (6 mL) was stirred at room temperature for 0.5 h. Then NaBH3CN (72.88 mg, 1.16 mmol, 5.49 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 20 mL of water and then extracted with 3×50 mL of chloroform/iso-propanol(3/1) and the organic layers combined and concentrated under vacuum. The crude product (98 mg) was purified by preparative HPLC under the following conditions (Waters): column: column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 50 mL NH4CO3 and CH3CN (5.0% CH3CN up to 44.0% in 12 min, up to 95.0% in 2 min, down to 5.0% in 2 min); Detector, 254/220 nm. This resulted in 34.6 mg (39%) of (2R)-1-[(3R)-12-[[4-(dimethylamino)-4-ethylcyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol as an off-white solid. MS: 418 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 8.47 (1H, s), 5.33-5.42 (1H, m), 3.68 (1H, m), 3.42-3.45 (1H, m), 3.00-3.14 (1H, m), 2.92-2.98 (1H, m), 2.70-2.73 (1H, m),2.50-2.67 (1H, m), 2.31-2.45 (1H, m), 2.06-2.11 (3H, m), 1.41-1.82 (11H, m), 0.91-1.05 (6H, m).

Workup

  1. customto react
  2. customThe reaction was then quenched by the addition of 20 mL of water
  3. extractionextracted with 3×50 mL of chloroform/iso-propanol(3/1)
  4. concentrationconcentrated under vacuum
  5. customThe crude product (98 mg) was purified by preparative HPLC under the following conditions (Waters)
  6. waitmobile phase: water with 50 mL NH4CO3 and CH3CN (5.0% CH3CN up to 44.0% in 12 min
  7. waitup to 95.0% in 2 min
  8. waitdown to 5.0% in 2 min)
  9. customThis resulted in 34.6 mg (39%) of (2R)-1-[(3R)-12-[[4-(dimethylamino)-4-ethylcyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol as an off-white solid

Sources & evidence

ORD record
ord-ce53d7b394974965b556be29e8348748
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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