1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-tert-butyl 3-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate

HRID 79528Notes

Reaction equation

HRID 79528 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[C:10]3[CH:16]=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[C:23]([O:27][C:28]([NH:30][C@H:31]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:32](O)=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][C@@H:31]([NH:30][C:28](=[O:29])[O:27][C:23]([CH3:25])([CH3:24])[CH3:26])[C:32]([N:20]2[CH2:19][CH2:18][N:17]([C:9]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[CH:13][N:12]=[C:11]4[NH:14][CH:15]=[CH:16][C:10]=34)[CH2:22][CH2:21]2)=[O:33])=[CH:37][CH:38]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 687604025-(3-fluorophenyl)-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 68761478(R)-tert-butyl 3-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamateYield 46.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(3-Fluorophenyl)-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyri dine (0.062 g, 0.168 mmol) and (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.0604 g, 0.201 mmol) were placed in DCM (3 mL) at room temperature. HOBT-H2O (0.0360 g, 0.235 mmol), EDCI (0.0418 g, 0.218 mmol), and DIEA (d 0.742; 0.146 mL, 0.840 mmol) were then added. The reaction was stirred at room temperature for 2 hours. The reaction was then quenched with saturated Na2CO3 and extracted with DCM. The organic fractions were dried, filtered, and concentrated to give a crude oil. The oil was purified by column chromatography (500:5 D CM: MeOH) to give (R)-tert-butyl 3-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate (0.045 g, 46.3% yield).

Workup

  1. customThe reaction was then quenched with saturated Na2CO3
  2. extractionextracted with DCM
  3. customThe organic fractions were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude oil
  7. customThe oil was purified by column chromatography (500:5 D CM: MeOH)

Sources & evidence

ORD record
ord-29230f5c26974c68aee1097b26a6e3b8
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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