Trimethyl orthoformate → (s)-5-(4-(3-Methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

HRID 881571Notes

Reaction equation

HRID 881571 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-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:34][S:35]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)(=[O:37])=[O:36].COC(OC)OC.[NH2:51][C:52]1[N:57]=[CH:56][C:55](B2OC(C)(C)C(C)(C)O2)=[CH:54][N:53]=1.CC([O-])=O.[K+]>O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC#N.ClCCCl.CC(O)=O>[CH3:19][C@@H:14]1[N:13]([C:4]2[C:5]3[S:10][C:9]([CH2:11][N:41]4[CH2:42][CH2:43][N:38]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:39][CH2:40]4)=[CH:8][C:6]=3[N:7]=[C:2]([C:55]3[CH:54]=[N:53][C:52]([NH2:51])=[N:57][CH:56]=3)[N:3]=2)[CH2:18][CH2:17][O:16][CH2:15]1

Participants

13

Reactant 6

HCID 9005Trimethyl orthoformateHCID 517044Potassium AcetateHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 58234096(S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde

Product 1

HCID 24948167(s)-5-(4-(3-Methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Following General Procedure D: (S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde (110 mg, 0.37 mmol), HOAc (22 mg), NaBH(OAc)3 (94 mg, 0.44 mmol), 1-methanesulfonyl piperazine (70 mg, 0.43 mmol), 1,2-dichloroethane (1.0 mL), trimethylorthoformate at room temperature for 1 h. The crude product was used in the next step without purification. MS (Q1) 445 (M)+. Following general procedure A: crude product from above, 2-aminopyrimidine-5-boronic acid pinacol ester (106 mg, 0.48 mmol), Pd(PPh3)4 (30 mg), MeCN (1.5 mL) and 1M KOAc in H2O (1.5 mL) were irradiated at 140° C. for 30 min. The reaction mixture was diluted with CH2Cl2, and filtered. The filtrate was concentrated to give 424, purified by reverse phase HPLC. (28 mg) MS (Q1) 505 (M).

Workup

  1. customThe crude product was used in the next step without purification
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-c50a839ca5db47af9a7cb3e9da9c6b02
Source dataset
uspto-grants-2015_03
Patent number
US08993563B2

Reaction notes

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