Isopropanol → 4-{4-[4-(3-Difluoromethyl-4-fluorophenyl)-1-(((R)-1-methylpiperidin-2-yl)methyl)-1H-imidazol-2-yl]-piperidin-1-yl}-5-ethyl-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one

HRID 1685208

Reaction equation

HRID 1685208 reaction equation
[F:1][CH:2]([F:29])[C:3]1[CH:4]=[C:5]([C:10]2[N:11]=[C:12]([CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[N:13]([CH2:15][C@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][N:17]3[CH3:22])[CH:14]=2)[CH:6]=[CH:7][C:8]=1[F:9].Cl[C:31]1[C:32]2[CH:39]([CH2:40][CH3:41])[C:38](=[O:42])[NH:37][C:33]=2[N:34]=[CH:35][N:36]=1.CCN(C(C)C)C(C)C.CC(O)C>O>[F:29][CH:2]([F:1])[C:3]1[CH:4]=[C:5]([C:10]2[N:11]=[C:12]([CH:23]3[CH2:24][CH2:25][N:26]([C:31]4[C:32]5[CH:39]([CH2:40][CH3:41])[C:38](=[O:42])[NH:37][C:33]=5[N:34]=[CH:35][N:36]=4)[CH2:27][CH2:28]3)[N:13]([CH2:15][C@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][N:17]3[CH3:22])[CH:14]=2)[CH:6]=[CH:7][C:8]=1[F:9]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 593223624-Chloro-5-ethyl-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-oneHCID 67265238(R)-2-((4-(3-(Difluoromethyl)-4-fluorophenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)methyl)-1-methylpiperidine

Product 1

HCID 672649364-{4-[4-(3-Difluoromethyl-4-fluorophenyl)-1-(((R)-1-methylpiperidin-2-yl)methyl)-1H-imidazol-2-yl]-piperidin-1-yl}-5-ethyl-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-oneYield 5.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Combine (R)-2-((4-(3-(difluoromethyl)-4-fluorophenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)methyl)-1-methylpiperidine (0.8 g, 0.0018 mol, 1.0 eq); 4-chloro-5-ethyl-5,7 dihydro-pyrrolo[2,3-d]pyrimidin-6-one (0.425 g, 0.00216 mol, 1.2 eq); DIPEA (2.3 mL, 0.0126 mol, 7.0 eq) and IPA (15 mL) in a pressure tube and heat at 120° C. overnight under sealed condition. Cool the reaction mass and dilute with water (25 mL). Extract in EA (2×50 mL) and wash the organic layer with brine (2×50 mL). Dry over anhydrous sodium sulfate and concentrate the crude compound. Filter the crude product through a short silica pad (100-200 mesh) using 0-8% MeOH-DCM). LCMS of concentrated crude product shows 70% of the desired product (m/z=568 [M+H]). Purify through reverse phase preparative HPLC to get 0.055 g of the title compound. MS (ES+): m/z=568 (M+H).

Workup

  1. customunder sealed condition
  2. temperatureCool the reaction mass
  3. extractionExtract in EA (2×50 mL)
  4. washwash the organic layer with brine (2×50 mL)
  5. dry with materialDry over anhydrous sodium sulfate
  6. concentrationconcentrate the crude compound
  7. filtrationFilter the crude product through a short silica pad (100-200 mesh)
  8. concentrationLCMS of concentrated crude product
  9. customPurify through reverse phase preparative HPLC

Sources & evidence

ORD record
ord-b7c4cb323d7c40748534993aff8bbe4a
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Linked notes

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