Diisopropylethylamine → HCID 67458556, compound

HRID 625071Notes

Reaction equation

HRID 625071 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH3:27][C@@H:28]1[C:36]2[C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[N:34][CH:33]=[N:32][C:31]=2[CH2:30][S:29]1.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][C:53]([C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([Cl:65])[CH:60]=2)([C:56](O)=[O:57])[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:65][C:61]1[CH:60]=[C:59]([C:53]2([C:56]([N:40]3[CH2:41][CH2:42][N:37]([C:35]4[C:36]5[C@@H:28]([CH3:27])[S:29][CH2:30][C:31]=5[N:32]=[CH:33][N:34]=4)[CH2:38][CH2:39]3)=[O:57])[CH2:52][CH2:51][N:50]([C:48]([O:47][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:49])[CH2:55][CH2:54]2)[CH:64]=[CH:63][CH:62]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450744981-(tert-Butoxycarbonyl)-4-(3-chlorophenyl)piperidine-4-carboxylic acidHCID 67459811HCID 67459811, compound

Product 1

HCID 67458556HCID 67458556, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HBTU (0.07726 g, 0.2037 mmol) was added to a solution of (R)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (0.030 g, 0.09701 mmol), 1-(tert-butoxycarbonyl)-4-(3-chlorophenyl)piperidine-4-carboxylic acid (0.06593 g, 0.1940 mmol), and DIEA (0.06759 ml, 0.3880 mmol) in DCM (2.5 mL). The reaction mixture was stirred overnight (18 hours), after which, saturated NaHCO3 was added. The mixture was extracted with DCM, and the extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on Biotage 12M (DCM flushed to remove DIEA, then 2:1 to 1:1 DCM:EA; top spot [by-prod] eluted quickly, then 2nd spot [prod]) to give (R)-tert-butyl 4-(3-chlorophenyl)-4-(4-(5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate. This was dissolved in dioxane (2 mL), and 4M HCl/dioxane (0.7275 ml, 2.910 mmol) was added, causing slow precipitation. The reaction mixture was stirred at room temperature overnight (18 hours), after which it was concentrated to dryness. The solids were dissolved in minimal MeOH, and then the product was triturated by the addition of ether. The resulting solids were isolated by filtration thru medium frit funnel with nitrogen pressure, rinsed with ether, and dried in vacuo to give (R)-(4-(3-chlorophenyl)piperidin-4-yl)(4-(5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)methanone dihydrochloride (0.029 g, 56.31% yield) as a pale yellow powder.

Workup

  1. extractionThe mixture was extracted with DCM
  2. dry with materialthe extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customflushed
  6. customto remove DIEA
  7. washtop spot [by-prod] eluted quickly

Sources & evidence

ORD record
ord-e5614135ede040b8ac9836834c06b3b3
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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