Water → tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamate

HRID 577703Notes

Reaction equation

HRID 577703 reaction equation
Cl[C:2]1[C:3]2[C:17]([Cl:18])=[CH:16][NH:15][C:4]=2[N:5]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[N:7]=1.[NH:19]1[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:20]1.CCN(C(C)C)C(C)C.O>CS(C)=O>[Cl:18][C:17]1[C:3]2[C:2]([N:19]3[CH2:24][CH2:23][CH2:22][CH:21]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:20]3)=[N:7][C:6]([NH:8][C:9]3[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=3)=[N:5][C:4]=2[NH:15][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 866796474,5-dichloro-N-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 86679648tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamateYield 44%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 4,5-dichloro-N-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (85 mg, 0.30 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (90 mg, 0.45 mmol) and DIEA (75 μL, 0.45 mmol) in DMSO (0.60 mL) was heated to 120° C. in a microwave for 10 min. The reaction solution was poured into water and filtered. The filtrate was extracted with EtOAc and the organic layer was dried over MgSO4, filtered and concentrated in vacuo. The solids were combined and purified via flash chromatography eluting with a gradient of 1%-5% of (10% NH4OH in MeOH) in DCM to give the title compound (59 mg, 44% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.38 (br. s., 1H), 8.74 (s, 1H), 7.82 (s, 1H), 7.49 (s, 1H), 7.04 (d, J=2.69 Hz, 1H), 6.89 (d, J=7.83 Hz, 1H), 3.96-4.11 (m, 2H), 3.78 (s, 3H), 3.51 (br. s., 1H), 2.85 (t, J=11.25 Hz, 1H), 2.75 (t, J=11.13 Hz, 1H), 1.85-1.94 (m, 1H), 1.75-1.84 (m, 1H), 1.70 (t, J=12.10 Hz, 1H), 1.38 (s, 9H), 1.31 (br. s., 1H). m/z (APCI+) for C20H27ClN8O2 447.2 (M+H)+.

Workup

  1. filtrationfiltered
  2. extractionThe filtrate was extracted with EtOAc
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified via flash chromatography
  7. washeluting with a gradient of 1%-5% of (10% NH4OH in MeOH) in DCM

Sources & evidence

ORD record
ord-5be913d99ae7404c95496b8506cb8f8e
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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