Trimethyl orthoformate → (S)-3-methyl-4-(6-((4-methylpiperazin-1-yl)methyl)-2-(pyrimidin-5-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine

HRID 391150Notes

Reaction equation

HRID 391150 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[C:5]2[S:10][C:9]([CH:11]=O)=[CH:8][C:6]=2[N:7]=1.[BH-](O[C:30]([CH3:32])=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.COC(OC)OC>ClCCCl.CC(O)=O>[CH3:19][C@H:14]1[CH2:15][O:16][CH2:17][CH2:18][N:13]1[C:4]1[C:5]2[S:10][C:9]([CH2:11][N:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]3)=[CH:8][C:6]=2[N:7]=[C:2]([C:30]2[CH:32]=[N:7][CH:2]=[N:3][CH:4]=2)[N:3]=1

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 58234096(S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde

Product 1

HCID 24948169(S)-3-methyl-4-(6-((4-methylpiperazin-1-yl)methyl)-2-(pyrimidin-5-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

Following General Procedure D, (S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde (100 mg, 0.34 mmol), HOAc (25 mg), NaBH(OAc)3 (80 mg, 0.37 mmol), N-methylpiperazine (41 mg, 0.40 mmol), 1,2-dichloroethane (1.0 mL), trimethylorthoformate were reacted at room temperature. The crude product was used in the next step without purification. MS (Q1) 382 (M)+. Following General Procedure A, crude product from above, pyrimidine-5-boronic acid (27 mg), Pd(PPh3)4 (20 mg), MeCN (1 mL) and 1M KOAc in H2O (1 mL) were irradiated at 150° C. for 30 min. The reaction mixture was diluted with CH2Cl2, and filtered. The filtrate was concentrated to give crude 422 which was purified by reverse phase HPLC. (14 mg) MS (Q1) 426 (M)+

Workup

  1. customwere reacted at room temperature
  2. customThe crude product was used in the next step without purification
  3. customwere irradiated at 150° C. for 30 min
  4. additionThe reaction mixture was diluted with CH2Cl2
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customto give crude 422 which
  8. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7b21bba2047c4c99bb455428ff1a867f
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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