Diisopropylethylamine → HCID 178508112, compound

HRID 423001Notes

Reaction equation

HRID 423001 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][C:11]1([C:17]([NH:19][C@H:20]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:21][CH2:22][OH:23])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.Cl[C:32]1[N:40]=[CH:39][N:38]=[C:37]2[C:33]=1[N:34]=[CH:35][NH:36]2>C(O)CCC.CCOC(C)=O>[NH2:10][C:11]1([C:17]([NH:19][C@H:20]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:21][CH2:22][OH:23])=[O:18])[CH2:16][CH2:15][N:14]([C:32]2[N:40]=[CH:39][N:38]=[C:37]3[C:33]=2[N:34]=[CH:35][NH:36]3)[CH2:13][CH2:12]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 57750388(S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)piperidine-4-carboxamide2×HCID 178478393HCID 178478393, compound

Product 1

HCID 178508112HCID 178508112, compoundYield 51.2%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

DIPEA (0.335 mL, 1.92 mmol) was added to (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)piperidine-4-carboxamide (Intermediate 49) (200 mg, 0.64 mmol) and 6-chloro-9H-purine (99 mg, 0.64 mmol) in butan-1-ol (4 mL). The resulting solution was stirred at 60° C. for 18 hours. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 6% MeOH with ammonia in DCM. Pure fractions were evaporated to dryness to afford (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(9H-purin-6-yl)piperidine-4-carboxamide (141 mg, 51.1%) as a white solid.

Workup

  1. washwashed sequentially with water (25 mL) and saturated brine (25 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 6% MeOH with ammonia in DCM
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-f0da8cad03754777923612b9b8001215
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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