Triethylamine → (5-Chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-(3-morpholin-4-ylazetidin-1-yl)methanone

HRID 1922775Notes

Reaction equation

HRID 1922775 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[N:10]=[C:9]([C:11]([OH:13])=O)[S:8][C:6]=2[N:7]=1.C(Cl)(=O)C(Cl)=O.CCN(CC)CC.[NH:33]1[CH2:36][CH:35]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH2:34]1>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[N:10]=[C:9]([C:11]([N:33]3[CH2:36][CH:35]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[CH2:34]3)=[O:13])[S:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 134019734-(Azetidin-3-yl)morpholineHCID 866482365-Chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine-2-carboxylic acid

Product 1

HCID 59606054(5-Chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-(3-morpholin-4-ylazetidin-1-yl)methanoneYield 63.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine-2-carboxylic acid (301 mg, 1.0 mmol) in DCM (6 mL) was added oxalyl chloride (847 μL, 10.00 mmol) and the resulting mixture allowed to stir at r.t. for 1 h then concentrated in vacuo and azeotroped with toluene. The resulting yellow solid was suspended in a mixture of DCM (6 mL) and NEt3 (418 μL, 3.00 mmol) at 0° C. before the addition of 4-azetidin-3-ylmorpholine (142 mg, 1.00 mmol). The resulting mixture was warmed to r.t. after 1 h then stirred for a further 30 min. The reaction mixture was partitioned between DCM and H2O, the organic phase dried (Na2SO4) and concentrated in vacuo. The resulting residue was triturated with EtOAc and dried in vacuo affording the title compound as an off-white solid (269 mg, 63%)._LCMS (method H): RT 2.19 min [M+H]+ 425.3

Workup

  1. concentrationthen concentrated in vacuo
  2. customazeotroped with toluene
  3. temperatureThe resulting mixture was warmed to r.t. after 1 h
  4. stirringthen stirred for a further 30 min
  5. customThe reaction mixture was partitioned between DCM and H2O
  6. dry with materialthe organic phase dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was triturated with EtOAc
  9. customdried in vacuo

Sources & evidence

ORD record
ord-39d87dcb8fb34177885a10144c12fec1
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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