Hydrochloric Acid → HCID 86344072, compound

HRID 1504098Notes

Reaction equation

HRID 1504098 reaction equation
[C:1]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[C:7](=[C:8]([NH:17][CH:18]4[CH2:23][CH2:22][CH:21]([NH:24][C:25](=O)OC(C)(C)C)[CH2:20][CH2:19]4)[N:9]=[CH:10][N:11]=3)[C:6]1=2)(=[O:3])[NH2:2].Cl.[BH3-][C:34]#N.[Na+]>ClCCl>[CH3:34][N:24]([CH3:25])[CH:21]1[CH2:20][CH2:19][CH:18]([NH:17][C:8]2[N:9]=[CH:10][N:11]=[C:12]3[C:7]=2[C:6]2[C@@H:5]([CH2:4][C:1]([NH2:2])=[O:3])[CH2:16][CH2:15][C:14]=2[S:13]3)[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 86695260HCID 86695260, compound

Product 1

HCID 86344072HCID 86344072, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]amino]cyclohexyl)carbamate (187 mg, 0.42 mmol, 1.00 equiv) in dichloromethane (5 mL) was added hydrogen chloride (12 M, 1 mL). The resulting solution was stirred for 2 h at room temperature. After evaporation, the residue was dissolved in CH3OH (10 mL) and HCHO (1.5 mL) was added. The resulting solution was stirred for 1 h at room temperature. To the above solution was added NaBH3CN (79 mg, 1.26 mmol, 3.00 equiv). The resulting solution was allowed to react, with stirring, overnight at room temperature. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×50 mL of dichloromethane and the organic layers combined. The crude product (100 mg) was purified by preparative HPLC under the following conditions: Column: Xbridge Prep C18, 5 μm, 19*150 mm; mobile phase, water (with 50 mL NH4CO3) and CH3CN (10.0% CH3CN up to 32.0% in 10 min, up to 95.0% in 1 min, down to 10.0% in 2 min); UV detection at 254 nm. This procedure afforded 50 mg (32%) of 2-[(3R)-12-[[4-(dimethylamino)cyclohexyl]amino]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]acetamide as a white solid. MS (ES): m/z 374 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 1.35-1.60 (m, 4H), 1.95-2.04 (m, 2H), 2.09-2.10 (m, 2H), 2.28-2.38 (m, 7H), 2.40-2.45 (m, 3H), 2.68-2.80 (m, 1H), 2.89-2.30 (m, 1H), 3.05-3.15 (m, 1H), 4.05-4.15 (m, 1H), 3.87 (dd, J=14.1, 6.3 Hz, 1H), 8.23 (s, 1H).

Workup

  1. customAfter evaporation
  2. dissolutionthe residue was dissolved in CH3OH (10 mL)
  3. additionHCHO (1.5 mL) was added
  4. stirringThe resulting solution was stirred for 1 h at room temperature
  5. customto react
  6. stirringwith stirring, overnight at room temperature
  7. customThe reaction was then quenched by the addition of 10 mL of water
  8. extractionThe resulting solution was extracted with 2×50 mL of dichloromethane
  9. customThe crude product (100 mg) was purified by preparative HPLC under the following conditions
  10. waitmobile phase, water (with 50 mL NH4CO3) and CH3CN (10.0% CH3CN up to 32.0% in 10 min
  11. waitup to 95.0% in 1 min
  12. waitdown to 10.0% in 2 min)

Sources & evidence

ORD record
ord-8fceb6bd68864eba9af1c94d3a2c437b
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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