Diisopropylethylamine → 5-{2-[(3S)-3-methylmorpholin-4-yl]-7-[1-(propan-2-ylsulfonyl)azetidin-3-yl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrimidin-2-amine

HRID 1775464Notes

Reaction equation

HRID 1775464 reaction equation
Cl.Cl.[NH:3]1[CH2:6][CH:5]([N:7]2[C:11]3[N:12]=[C:13]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]4[CH3:29])[N:14]=[C:15]([C:16]4[CH:17]=[N:18][C:19]([NH2:22])=[N:20][CH:21]=4)[C:10]=3[CH2:9][CH2:8]2)[CH2:4]1.CCN(C(C)C)C(C)C.[CH:39]([S:42](Cl)(=[O:44])=[O:43])([CH3:41])[CH3:40]>C(Cl)Cl>[CH3:29][C@H:24]1[CH2:25][O:26][CH2:27][CH2:28][N:23]1[C:13]1[N:14]=[C:15]([C:16]2[CH:21]=[N:20][C:19]([NH2:22])=[N:18][CH:17]=2)[C:10]2[CH2:9][CH2:8][N:7]([CH:5]3[CH2:6][N:3]([S:42]([CH:39]([CH3:41])[CH3:40])(=[O:44])=[O:43])[CH2:4]3)[C:11]=2[N:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 824082-Propanesulfonyl chlorideHCID 1184362655-{7-(azetidin-3-yl)-2-[(3S)-3-methylmorpholin-4-yl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrimidin-2-amine dihydrochloride

Product 1

HCID 1184361655-{2-[(3S)-3-methylmorpholin-4-yl]-7-[1-(propan-2-ylsulfonyl)azetidin-3-yl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrimidin-2-amineYield 53.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 5-{7-(azetidin-3-yl)-2-[(3S)-3-methylmorpholin-4-yl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrimidin-2-amine dihydrochloride (100 mg, 0.20 mmol) in DCM (5.0 mL) was added DIPEA (0.2 mL, 1.15 mmol). After a few minutes, the mixture became almost homogeneous, and a fine precipitation began to form. The reaction mixture was cooled to 0° C. and isopropylsulfonyl chloride (0.023 mL, 0.21 mmol) was added. The mixture was stirred at 0° C. for 45 min resulting in an amber solution. The mixture was concentrated to a minimum volume and the residue was purified by SFC column to give 50.4 mg (51%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 2 H), 6.98 (s, 2 H), 4.80 (p, J=7.2 Hz, 1 H), 4.68-4.59 (m, 1H), 4.29-4.21 (m, 3 H), 3.98 (dt, J=7.9, 4.4 Hz, 2 H), 3.88 (dd, J=11.1, 3.0 Hz, 1 H), 3.72-3.65 (m, 3 H), 3.56 (dd, J=11.3, 2.9 Hz, 1 H), 3.40 (dt, J=11.7, 2.8 Hz, 1 H), 3.28-3.21 (m, 1H, partially overlapped with water), 3.15 (t, J=8.2 Hz, 2 H), 3.07 (dt, J=12.9, 3.7 Hz, 1 H), 1.24 (d, J=6.8 Hz, 6 H), 1.16 (d, J=6.7 Hz, 3 H). m/z (APCI+) for C21H30N8O3S 475.2 (M+H)+.

Workup

  1. waitAfter a few minutes
  2. customa fine precipitation
  3. customto form
  4. customresulting in an amber solution
  5. concentrationThe mixture was concentrated to a minimum volume
  6. customthe residue was purified by SFC column

Sources & evidence

ORD record
ord-24f9916113ea45d39316ea59ad749888
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

Loading…