Methanesulfonyl chloride → tert-butyl 3-{4-chloro-2[(3S)-3-methylmorpholin-4-yl]-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}azetidine-1-carboxylate

HRID 1775461Notes

Reaction equation

HRID 1775461 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[N:5]=[C:4]([NH:15][CH:16]2[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]2)[C:3]=1[CH2:27][CH2:28]O.CS(Cl)(=O)=O.C1CCN2C(=NCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C.[Cl-].[Na+].O>[Cl:1][C:2]1[C:3]2[CH2:27][CH2:28][N:15]([CH:16]3[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[CH2:17]3)[C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[N:7]=1

Participants

7

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 118436480tert-butyl 3-({6-chloro-5-(2-hydroxyethyl)-2-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl}amino)azetidine-1-carboxylate

Product 1

HCID 118436598tert-butyl 3-{4-chloro-2[(3S)-3-methylmorpholin-4-yl]-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}azetidine-1-carboxylateYield 83.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
15 °C

Procedure

A solution of tert-butyl 3-({6-chloro-5-(2-hydroxyethyl)-2-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl}amino)azetidine-1-carboxylate (0.1 g, 0.234 mmol) in DCM (4 mL) was treated with TEA (0.08 mL, 0.57 mmol) and methanesulfonyl chloride (0.026 mL, 0.34 mmol) at 0° C., followed by addition of a catalytic amount of DMAP. The reaction mixture was stirred for 2 h, letting the ice bath slowly warm to about 15° C. The reaction mixture was partitioned between DCM (2×10 mL) and water (10 mL). The organic layer was dried over MgSO4 and reduced to a minimum volume. The residue was taken up in DMF (5 mL), and DBU (0.13 mL, 0.85 mmol) was added. The resulting mixture was crimp sealed and heated at 75° C. for 4 h. The crude mixture was poured into a brine solution (50 mL) and the resulting white solids were collected by filtration and rinsed with water. The solids were dried in a vacuum oven at 50° C. overnight to provide (80 mg, 83%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 4.74-4.65 (m, 1 H), 4.49-4.41 (m, 1 H), 4.18-3.98 (m, 5 H), 3.84 (dd, J=11.3, 3.4 Hz, 1 H), 3.71 (t, J=8.7 Hz, 2 H), 3.66-3.61 (m, 1 H), 3.51 (dd, J=11.4, 3.1 Hz, 1 H), 3.36 (dt, J=11.8, 3.0 Hz, 1 H), 3.05 (dt, J=12.9, 3.7 Hz, 1 H), 2.85 (t, J=8.3 Hz, 2 H), 1.38 (s, 9 H), 1.13 (d, J=6.7 Hz, 3 H).

Workup

  1. customThe reaction mixture was partitioned between DCM (2×10 mL) and water (10 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. customThe resulting mixture was crimp sealed
  4. temperatureheated at 75° C. for 4 h
  5. filtrationthe resulting white solids were collected by filtration
  6. washrinsed with water
  7. customThe solids were dried in a vacuum oven at 50° C. overnight

Sources & evidence

ORD record
ord-17ecaaa8e9454cdc8796facec25d0f67
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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