Dichloromethane → (S)-2-(4-chlorophenyl)-3-(2-hydroxy-2-methylpropylamino)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one

HRID 75406Notes

Reaction equation

HRID 75406 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH3:25][C@H:26]1[C:34]2[C:33]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)=[N:32][CH:31]=[N:30][C:29]=2[C@H:28]([OH:41])[CH2:27]1.[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C@@H:49]([CH2:53][NH:54][CH2:55][C:56]([OH:59])([CH3:58])[CH3:57])[C:50](O)=[O:51])=[CH:45][CH:44]=1.C(Cl)Cl>>[Cl:42][C:43]1[CH:44]=[CH:45][C:46]([C@@H:49]([CH2:53][NH:54][CH2:55][C:56]([OH:59])([CH3:57])[CH3:58])[C:50]([N:38]2[CH2:37][CH2:36][N:35]([C:33]3[C:34]4[C@H:26]([CH3:25])[CH2:27][C@@H:28]([OH:41])[C:29]=4[N:30]=[CH:31][N:32]=3)[CH2:40][CH2:39]2)=[O:51])=[CH:47][CH:48]=1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59580358(5R,7R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-olHCID 68626158(S)-2-(4-chlorophenyl)-3-(2-hydroxy-2-methylpropylamino)propanoic acid

Product 1

HCID 44123659(S)-2-(4-chlorophenyl)-3-(2-hydroxy-2-methylpropylamino)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-oneYield 52%

Procedure

O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.100 g, 0.265 mmol) was added to a solution of (5R,7R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol (31 mg, 0.13 mmol), N,N-diisopropylethylanine (0.231 mL, 1.32 mmol) and (S)-2-(4-chlorophenyl)-3-(2-hydroxy-2-methylpropylamino)propanoic acid (43 mg, 0.16 mmol) in methylene chloride (1.2 mL, 19 mmol). The mixture was stirred for 1 hour at room temperature, after which the reaction was quenched with saturated aqueous NH4Cl. The mixture was extracted with DCM (3×10 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude product was purified by reverse phase HPLC to give (S)-2-(4-chlorophenyl)-3-(2-hydroxy -2-methylpropylamino)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one (33 mg, 51%). 1HNMR (CDCl3, 500 MHz) δ 8.59 (s, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.33 (d, J=8.5 Hz, 2H), 5.06 (m, 1H), 4.48 (m, 1H), 3.92 (m, 2H), 3.15 (m, 2H), 2.94 (m, 2H), 2.02 (m, 2H), 1.19 (m, 6H), 1.06 (d, 3H). LCMS M+1 488.3

Workup

  1. customafter which the reaction was quenched with saturated aqueous NH4Cl
  2. extractionThe mixture was extracted with DCM (3×10 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-0aae7d819a4f405d872e8608e8a31e0a
Source dataset
uspto-grants-2014_09
Patent number
US08835434B2

Reaction notes

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