Formaldehyde → HCID 86695205, compound

HRID 1504049Notes

Reaction equation

HRID 1504049 reaction equation
N[C:2]1([CH3:25])[CH2:7][CH2:6][CH:5]([O:8][C:9]2[C:20]3[C:19]4[C@@H:18]([CH2:21][C:22]([NH2:24])=[O: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.[CH2:26]=O.[BH3-][C:29]#[N:30].[Na+]>CO>[CH3:26][N:30]([CH3:29])[C:2]1([CH3:25])[CH2:7][CH2:6][CH:5]([O:8][C:9]2[C:20]3[C:19]4[C@@H:18]([CH2:21][C:22]([NH2:24])=[O: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

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86695206HCID 86695206, compound

Product 1

HCID 86695205HCID 86695205, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-[(3R)-12-[(4-amino-4-methylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide (200 mg, 0.55 mmol, 1.00 equiv) in 8 mL of methanol was added HCHO (37%, 1.2 mL). The solution was stirred for 0.5 h at room temperature. Then NaBH3CN (105 mg, 1.67 mmol, 3.01 equiv) was added and the resulting solution was allowed to react, with stirring, for an additional 1 h at room temperature. The reaction was quenched with NH4Cl (aq.) and extracted with 3×60 mL of DCM. The combined organic layers were concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC under the following conditions (Waters): column: XBridge Prep C18 OBD column: 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (5% CH3CN up to 47% in 13 min, up to 95% in 2 min, down to 5% in 2 min); flow rate: 20 mL/min; UV detection at 254 & 220 nm. This resulted in 39.8 mg of 2-[(3R)-12-[[4-(dimethylamino)-4-methylcyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide as a white solid. MS: m/z 389 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 8.49 (1H, s), 5.41 (1H, m), 3.80 (1H, m), 3.19 (1H, m), 3.04 (1H, m), 2.98 (1H, m), 2.85 (6H, s), 2.76 (1H, m), 2.31 (4H, m), 2.14 (2H, m), 1.96 (4H, m), 1.47 (3H, s).

Workup

  1. customto react
  2. stirringwith stirring, for an additional 1 h at room temperature
  3. customThe reaction was quenched with NH4Cl (aq.)
  4. extractionextracted with 3×60 mL of DCM
  5. concentrationThe combined organic layers were concentrated under vacuum
  6. customThe crude product (150 mg) was purified by preparative HPLC under the following conditions (Waters)
  7. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (5% CH3CN up to 47% in 13 min
  8. waitup to 95% in 2 min
  9. waitdown to 5% in 2 min)
  10. customThis resulted in 39.8 mg of 2-[(3R)-12-[[4-(dimethylamino)-4-methylcyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide as a white solid

Sources & evidence

ORD record
ord-50e6207491a04b86a8ed8a36157cb1ca
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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